Karyotypic changes and diversification time in Epinephelidae groupers (Perciformes). Implications on reproductive isolation.

Groupers (Epinephelidae and Serranidae) have attracted special attention to fish farming, and their species offer good opportunities for successful hybridizations. Cytogenetic data allow a better understanding of the role of karyotypic diversification in the acquisition of post-zygotic reproductive isolation (RI). Thus, chromosomal analyses were performed on E. striatus (Caribbean Sea), E. coioides and E. tauvina (Indo-Pacific Region), using standard procedures and mapping of six repetitive DNA classes by the in situ hybridization. The three species have 2n=48 chromosomes. The karyotypes of E. coioides and E. striatus are composed only of acrocentric chromosomes (FN=48), while E. tauvina has 8 submetacentric chromosomes (FN=56). Heterochromatin has a preferential centromeric distribution, and the microsatellite repeats are dispersed throughout the chromosomes of all species. The 18S and 5S rDNA sites are unique but show a colocalization arrangement in E. tauvina and E. striatus. The chromosomal organization suggests that the three species still maintain a significant amount of syntenic regions. The range of the karyotype divergence and the RI levels showed low, but goes turn proportionally greater in relation to the divergence time between the parental species. The slow acquisition of postzygotic RI is consistent with the high karyotype homogeneity presented by Epinephelidae family.

Cytogenetics Meets Genomics: Cytotaxonomy and Genomic Relationships among Color Variants of the Asian Arowana Scleropages formosus.

Scleropages formosus (Osteoglossiformes, Teleostei) represents one of the most valued ornamental fishes, yet it is critically endangered due to overexploitation and habitat destruction. This species encompasses three major color groups that naturally occur in allopatric populations, but the evolutionary and taxonomic relationships of S. formosus color varieties remain uncertain. Here, we utilized a range of molecular cytogenetic techniques to characterize the karyotypes of five S. formosus color phenotypes, which correspond to naturally occurring variants: the red ones (Super Red); the golden ones (Golden Crossback and Highback Golden); the green ones (Asian Green and Yellow Tail Silver). Additionally, we describe the satellitome of S. formosus (Highback Golden) by applying a high-throughput sequencing technology. All color phenotypes possessed the same karyotype structure 2n = 50 (8m/sm + 42st/a) and distribution of SatDNAs, but different chromosomal locations of rDNAs, which were involved in a chromosome size polymorphism. Our results show indications of population genetic structure and microstructure differences in karyotypes of the color phenotypes. However, the findings do not clearly back up the hypothesis that there are discrete lineages or evolutionary units among the color phenotypes of S. formosus, but another case of interspecific chromosome stasis cannot be excluded.

The Genetic Differentiation of Pyrrhulina (Teleostei, Characiformes) Species is Likely Influenced by Both Geographical Distribution and Chromosomal Rearrangements.

Allopatry is generally considered to be one of the main contributors to the remarkable Neotropical biodiversity. However, the role of chromosomal rearrangements including neo-sex chromosomes for genetic diversity is still poorly investigated and understood. Here, we assess the genetic divergence in five Pyrrhulina species using population genomics and combined the results with previously obtained cytogenetic data, highlighting that molecular genetic diversity is consistent with their chromosomal features. The results of a principal coordinate analysis (PCoA) indicated a clear difference among all species while showing a closer relationship of the ones located in the same geographical region. This was also observed in genetic structure analyses that only grouped P. australis and P. marilynae, which were also recovered as sister species in a species tree analysis. We observed a contradictory result for the relationships among the three species from the Amazon basin, as the phylogenetic tree suggested P. obermulleri and P. semifasciata as sister species, while the PCoA showed a high genetic difference between P. semifasciata and all other species. These results suggest a potential role of sex-related chromosomal rearrangements as reproductive barriers between these species.

Integrating Cytogenetics and Population Genomics: Allopatry and Neo-Sex Chromosomes May Have Shaped the Genetic Divergence in the Erythrinus erythrinus Species Complex (Teleostei, Characiformes).

Diversity found in Neotropical freshwater fish is remarkable. It can even hinder a proper delimitation of many species, with the wolf fish Erythrinus erythrinus (Teleostei, Characiformes) being a notable example. This nominal species shows remarkable intra-specific variation, with extensive karyotype diversity found among populations in terms of different diploid chromosome numbers (2n), karyotype compositions and sex chromosome systems. Here, we analyzed three distinct populations (one of them cytogenetically investigated for the first time) that differed in terms of their chromosomal features (termed karyomorphs) and by the presence or absence of heteromorphic sex chromosomes. We combined cytogenetics with genomic approaches to investigate how the evolution of multiple sex chromosomes together with allopatry is linked to genetic diversity and speciation. The results indicated the presence of high genetic differentiation among populations both from cytogenetic and genomic aspects, with long-distance allopatry potentially being the main agent of genetic divergence. One population showed a neo-X1X2Y sexual chromosome system and we hypothesize that this system is associated with enhanced inter-population genetic differentiation which could have potentially accelerated speciation compared to the effect of allopatry alone.

CIRRHOTIC PATIENTS WITH ACUTE KIDNEY INJURY (AKI) HAVE HIGHER MORTALITY AFTER ABDOMINAL HERNIA SURGERY.

BACKGROUND: The incidence of abdominal hernia in cirrhotic patients is as higher as 20%; in cases of major ascites the incidence may increase up to 40%. One of the main and most serious complications in cirrhotic postoperative period (PO) is acute kidney injury (AKI). AIM: To analyze the renal function of cirrhotic patients undergoing to hernia surgery and evaluate the factors related to AKI. METHODS: Follow-up of 174 cirrhotic patients who underwent hernia surgery. Laboratory tests including the renal function were collected in the PO.AKI was defined based on the consensus of the ascite´s club. They were divided into two groups: with (AKI PO) and without AKI . RESULTS: All 174 patients were enrolled and AKI occurred in 58 (34.9%). In the AKI PO group, 74.1% had emergency surgery, whereas in the group without AKI PO it was only 34.6%.In the group with AKI PO, 90.4% presented complications, whereas in the group without AKI PO they occurred only in 29.9%. Variables age, baseline MELD, baseline creatinine, creatinine in immediate postoperative (POI), AKI and the presence of ascites were statistically significant for survival. CONCLUSIONS: There is association between AKI PO and emergency surgery and, also, between AKI PO and complications after surgery. The factors related to higher occurrence were initial MELD, basal Cr, Cr POI. The patients with postoperative AKI had a higher rate of complications and higher mortality.

Adding New Pieces to the Puzzle of Karyotype Evolution in Harttia (Siluriformes, Loricariidae): Investigation of Amazonian Species.

A remarkable morphological diversity and karyotype variability can be observed in the Neotropical armored catfish genus Harttia. These fishes offer a useful model to explore both the evolution of karyotypes and sex chromosomes, since many species possess male-heterogametic sex chromosome systems and a high rate of karyotype repatterning. Based on the karyotype organization, the chromosomal distribution of several repetitive DNA classes, and the rough estimates of genomic divergences at the intraspecific and interspecific levels via Comparative Genomic Hybridization, we identified shared diploid chromosome numbers (2n = 54) but different karyotype compositions in H. dissidens (20m + 26sm + 8a) and Harttia sp. 3 (16m + 18sm + 14st + 6a), and different 2n in H. guianensis (2n = 58; 20m + 26sm + 2st + 10a). All species further displayed similar patterns of chromosomal distribution concerning constitutive heterochromatin, 18S ribosomal DNA (rDNA) sites, and most of the surveyed microsatellite motifs. Furthermore, differences in the distribution of 5S rDNA sites and a subset of microsatellite sequences were identified. Heteromorphic sex chromosomes were lacking in H. dissidens and H. guianensis at the scale of our analysis. However, one single chromosome pair in Harttia sp. 3 males presented a remarkable accumulation of male genome-derived probe after CGH, pointing to a tentative region of early sex chromosome differentiation. Thus, our data support already previously outlined evidence that Harttia is a vital model for the investigation of teleost karyotype and sex chromosome dynamics.

Revisiting the Karyotypes of Alligators and Caimans (Crocodylia, Alligatoridae) after a Half-Century Delay: Bridging the Gap in the Chromosomal Evolution of Reptiles.

Although crocodilians have attracted enormous attention in other research fields, from the cytogenetic point of view, this group remains understudied. Here, we analyzed the karyotypes of eight species formally described from the Alligatoridae family using differential staining, fluorescence in situ hybridization with rDNA and repetitive motifs as a probe, whole chromosome painting (WCP), and comparative genome hybridization. All Caimaninae species have a diploid chromosome number (2n) 42 and karyotypes dominated by acrocentric chromosomes, in contrast to both species of Alligatorinae, which have 2n = 32 and karyotypes that are predominantly metacentric, suggesting fusion/fission rearrangements. Our WCP results supported this scenario by revealing the homeology of the largest metacentric pair present in both Alligator spp. with two smaller pairs of acrocentrics in Caimaninae species. The clusters of 18S rDNA were found on one chromosome pair in all species, except for Paleosuchus spp., which possessed three chromosome pairs bearing these sites. Similarly, comparative genomic hybridization demonstrated an advanced stage of sequence divergence among the caiman genomes, with Paleosuchus standing out as the most divergent. Thus, although Alligatoridae exhibited rather low species diversity and some level of karyotype stasis, their genomic content indicates that they are not as conserved as previously thought. These new data deepen the discussion of cytotaxonomy in this family.

Chromosomal Analysis of Ctenolucius hujeta Valenciennes, 1850 (Characiformes): A New Piece in the Chromosomal Evolution of the Ctenoluciidae.

Ctenoluciidae (Characiformes), a family of freshwater fishes, comprises 2 genera, Ctenolucius and Boulengerella, with 7 recognized species. Up to now, only species of the genus Boulengerella have been subjected to cytogenetic studies. Here, we investigated the karyotype and other cytogenetic features of pike characin, Ctenolucius hujeta, using conventional (Giemsa staining, C-banding, Ag-NOR staining) and molecular (rDNA, telomeric sequences, and fiber-FISH mapping) procedures. This species has a diploid chromosome number of 2n = 36, and a karyotype composed of 12m + 20sm + 4a and FN = 68, similar to that found in Boulengerella species. However, differences regarding the number and distribution of several chromosomal markers support a distinct generic status. Colocalization of the 18S and 5S rDNA genes is an exclusive characteristic of the C. hujeta genome, with an interspersed distribution in the chromosomal fiber, an unusual phenomenon among eukaryotes. Additionally, our results support the view that Ctenoluciidae and Lebiasinidae families are closely related.

High Genetic Diversity despite Conserved Karyotype Organization in the Giant Trahiras from Genus Hoplias (Characiformes, Erythrinidae).

In the fish genus Hoplias, two major general groups can be found, one of which is formed by the "common trahiras" (Hoplias malabaricus group) and the other by the "giant trahiras" (Hoplias lacerdae group, in addition to Hoplias aimara), which usually comprises specimens of larger body size. Previous investigations from the giant trahiras group recovered 2n = 50 meta/submetacentric chromosomes and no sex chromosome differentiation, indicating a probable conservative pattern for their karyotype organization. Here, we conducted comparative cytogenetic studies in six giant trahiras species, two of them for the first time. We employed standard and advanced molecular cytogenetics procedures, including comparative genomic hybridization (CGH), as well as genomic assessments of diversity levels and phylogenetic relationships among them. The results strongly suggest that the giant trahiras have a particular and differentiated evolutionary pathway inside the Hoplias genus. While these species share the same 2n and karyotypes, their congeneric species of the H. malabaricus group show a notable chromosomal diversity in number, morphology, and sex chromosome systems. However, at the same time, significant changes were characterized at their inner chromosomal level, as well as in their genetic diversity, highlighting their current relationships resulting from different evolutionary histories.

Cirrhotic patients with acute kidney injury (aki) have higher mortality after abdominal hernia surgery / Pacientes cirróticos com lesão renal aguda tem maior mortalidade após cirurgia de hérnia abdominal

ABSTRACT Background: The incidence of abdominal hernia in cirrhotic patients is as higher as 20%; in cases of major ascites the incidence may increase up to 40%. One of the main and most serious complications in cirrhotic postoperative period (PO) is acute kidney injury (AKI). Aim: To analyze the renal function of cirrhotic patients undergoing to hernia surgery and evaluate the factors related to AKI. Methods: Follow-up of 174 cirrhotic patients who underwent hernia surgery. Laboratory tests including the renal function were collected in the PO.AKI was defined based on the consensus of the ascite´s club. They were divided into two groups: with (AKI PO) and without AKI . Results: All 174 patients were enrolled and AKI occurred in 58 (34.9%). In the AKI PO group, 74.1% had emergency surgery, whereas in the group without AKI PO it was only 34.6%.In the group with AKI PO, 90.4% presented complications, whereas in the group without AKI PO they occurred only in 29.9%. Variables age, baseline MELD, baseline creatinine, creatinine in immediate postoperative (POI), AKI and the presence of ascites were statistically significant for survival. Conclusions: There is association between AKI PO and emergency surgery and, also, between AKI PO and complications after surgery. The factors related to higher occurrence were initial MELD, basal Cr, Cr POI. The patients with postoperative AKI had a higher rate of complications and higher mortality.

RESUMO Racional: A incidência de hérnia abdominal em pacientes cirróticos é elevada, em torno de 20%. Em casos de ascite volumosa, a incidência atinge valores até 40%. Uma das principais e mais graves complicações no pós-operatório de correção de hérnias de pacientes cirróticos é a insuficiência renal aguda (IRA). Objetivo: Analisar a função renal de pacientes cirróticos submetidos a herniorrafias, comparando aqueles que apresentavam IRA pós-operatório com os demais, para determinar os fatores relacionados à sua ocorrência. Método: Seguimento de pacientes cirróticos submetidos à cirurgia de hérnia entre 2001 e 2014 no Serviço de Transplante de Fígado. Foram coletados exames laboratoriais para avaliar a função renal no pós-operatório rotineiramente. A IRA foi definida com base no consenso do clube da ascite em 2015. Resultados: Dos 174 pacientes incluídos, ocorreu IRA em 58 pacientes (34,9%). Houve diferença entre grupos para as seguintes variáveis: MELD inicial, creatinina basal e creatinina, o grupo com IRA apresentou medias superiores ao grupo que não apresentou IRA. No grupo IRA PO, 74,1% das cirurgias, foram realizadas em caráter de emergência, enquanto que no grupo sem IRA no pós-operatório, 34,6%. No grupo IRA, 90,4% dos indivíduos apresentaram complicações no pós-operatório, enquanto no grupo sem IRA, 29,9%. As variáveis idade, MELD inicial, creatinina basal e creatinina no pós-operatório inicial foram estatisticamente significantes na análise de sobrevida. Conclusões: Existe uma associação entre IRA pós-operatória e cirurgia de emergência e IRA pós-operatóri e complicações pós-operatórias. Os fatores relacionados à maior ocorrência de IRA em pacientes cirróticos submetidos à cirurgia de hérnia são o MELD inicial, creatinina basal, creatinina pós-operatória inicial. O preparo de pacientes cirróticos com hérnia abdominal antes de procedimentos cirúrgicos deve ocorrer sistematicamente, pois apresentam alta incidência de IRA pós-operatória.

Chromosomes of Asian cyprinid fishes: Variable karyotype patterns and evolutionary trends in the genus Osteochilus (Cyprinidae, Labeoninae, "Osteochilini").

The Cyprinidae family is a highly diversified but demonstrably monophyletic lineage of cypriniform fishes. Among them, the genus Osteochilus contains 35 recognized valid species distributed from India, throughout Myanmar, Laos, Thailand, Malaysia, Indonesian archipelago to southern China. In this study, karyotypes and other chromosomal characteristics of five Osteochilus species occurring in Thailand, namely O. lini, O. melanopleura, O. microcephalus, O. vittatus and O. waandersii were examined using conventional and molecular cytogenetic protocols. Our results showed they possessed diploid chromosome number (2n) invariably 2n = 50, but the ratio of uni- and bi-armed chromosomes was highly variable among their karyotypes, indicating extensive chromosomal rearrangements. Only one chromosome pair bearing 5S rDNA sites occurred in most species, except O. melanopleura, where two sites were detected. In contrast, only one chromosomal pair bearing 18S rDNA sites were observed among their karyotypes, but in different positions. These cytogenetic patterns indicated that the cytogenomic divergence patterns of these Osteochilus species were largely corresponding to the inferred phylogenetic tree. Similarly, different patterns of the distributions of rDNAs and microsatellites across genomes of examined species as well as their different karyotype structures indicated significant evolutionary differentiation of Osteochilus genomes.

Chromosomal Evolution in Aspredinidae (Teleostei, Siluriformes): Insights on Intra- and Interspecific Relationships with Related Groups.

The family Aspredinidae comprises a clade of complex systematic relationships, both from molecular and morphological approaches. In this study, conventional and molecular cytogenetic studies coupled with nucleotide sequencing were performed in 6 Aspredininae species (Amaralia hypsiura, Bunocephalus cf. aloikae, Bunocephalus amaurus, Bunocephalus aff. coracoideus, Bunocephalus verrucosus, and Platystacus cotylephorus) from different locations of the Amazon hydrographic basin. Our results showed highly divergent diploid numbers (2n) among the species, ranging from 49 to 74, including the occurrence of an XX/X0 sex chromosome system. A neighbor-joining phylogram based on the cytochrome c oxidase I (COI) showed that Bunocephalus coracoideus is not a monophyletic clade, but closely related to B. verrucosus. The karyotypic data associated with COI suggest an ancestral karyotype for Aspredinidae with a reduced 2n, composed of bi-armed chromosomes and a trend toward chromosomal fissions resulting in higher diploid number karyotypes, mainly composed of acrocentric chromosomes. Evolutionary relationships were discussed under a phylogenetic context with related species from different Siluriformes families. The karyotype features and chromosomal diversity of Aspredinidae show an amazing differentiation, making this family a remarkable model for investigating the evolutionary dynamics in siluriforms as well as in fish as a whole.

Multiple Sex Chromosomes and Evolutionary Relationships in Amazonian Catfishes: The Outstanding Model of the Genus Harttia (Siluriformes: Loricariidae).

The armored Harttia catfishes present great species diversity and remarkable cytogenetic variation, including different sex chromosome systems. Here we analyzed three new species, H. duriventris, H. villasboas and H. rondoni, using both conventional and molecular cytogenetic techniques (Giemsa-staining and C-banding), including the mapping of repetitive DNAs using fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) experiments. Both H. duriventris and H. villasboas have 2n = ♀56/♂55 chromosomes, and an X1X1X2X2 /X1X2Y sex chromosome system, while a proto or neo-XY system is proposed for H. rondoni (2n = 54♀♂). Single motifs of 5S and 18S rDNA occur in all three species, with the latter being also mapped in the sex chromosomes. The results confirm the general evolutionary trend that has been noticed for the genus: an extensive variation on their chromosome number, single sites of rDNA sequences and the occurrence of multiple sex chromosomes. Comparative genomic analyses with another congeneric species, H. punctata, reveal that the X1X2Y sex chromosomes of these species share the genomic contents, indicating a probable common origin. The remarkable karyotypic variation, including sex chromosomes systems, makes Harttia a suitable model for evolutionary studies focusing on karyotype differentiation and sex chromosome evolution among lower vertebrates.

An Insight into the Chromosomal Evolution of Lebiasinidae (Teleostei, Characiformes).

Lebiasinidae fishes have been historically neglected by cytogenetical studies. Here we present a genomic comparison in eleven Lebiasinidae species, in addition to a review of the ribosomal DNA sequences distribution in this family. With that, we develop ten sets of experiments in order to hybridize the genomic DNA of representative species from the genus Copeina, Copella, Nannostomus, and Pyrrhulina in metaphase plates of Lebiasina melanoguttata. Two major pathways on the chromosomal evolution of these species can be recognized: (i) conservation of 2n = 36 bi-armed chromosomes in Lebiasininae, as a basal condition, and (ii) high numeric and structural chromosomal rearrangements in Pyrrhulininae, with a notable tendency towards acrocentrization. The ribosomal DNA (rDNA) distribution also revealed a marked differentiation during the chromosomal evolution of Lebiasinidae, since both single and multiple sites, in addition to a wide range of chromosomal locations can be found. With some few exceptions, the terminal position of 18S rDNA appears as a common feature in Lebiasinidae-analyzed species. Altogether with Ctenoluciidae, this pattern can be considered a symplesiomorphism for both families. In addition to the specific repetitive DNA content that characterizes the genome of each particular species, Lebiasina also keeps inter-specific repetitive sequences, thus reinforcing its proposed basal condition in Lebiasinidae.

Molecular Cytogenetic Analysis in Freshwater Prawns of the Genus Macrobrachium (Crustacea: Decapoda: Palaemonidae).

Freshwater prawns of the genus Macrobrachium are one of the important components of circumtropical marine, estuarine, and freshwater environments. They have been extensively exploited for human consumption for many years. More than 250 species reflect the evolutionary success of this highly diversified group, with a complex and challenging taxonomy due to morphological variations and vast geographical distribution. Although genetic approaches have been used to clarify phylogenetic and taxonomic aspects of Macrobrachium species, cytogenetic information is still very scarce and mostly focused on chromosome number and morphology. Here, we present chromosome data for three species from the Neotropical region, M. carcinus, M. acanthurus, and M. amazonicum, and one species from the Oriental region, M. rosenbergii. Using conventional cytogenetic approaches and chromosome mapping of repetitive DNAs by fluorescence in situ hybridization (FISH), we identified numerical diversification of the diploid set, within and between both zoogeographic regions. These included M. acanthurus and M. amazonicum sharing diploid chromosomes of 98, while M. carcinus has 94, and M. rosenbergii has 118 chromosomes. Argentophilic sites are also variable in number, but they occur in a much higher number than 18S rDNA, representing two to 10 sites within the study species. Microsatellites repeat motifs are also abundant in the chromosomes, with a co-localization and uniform distribution along the chromosome arms, but completely absent in the AT-rich centromeric regions. As a whole, our study suggests that the 2n divergence was followed by a considerable rDNA diversification. The abundance of the exceptional amount of microsatellite sequences in the chromosomes also suggests that they are essential components of the Macrobrachium genome and, therefore, maintained as a shared feature by the species, the reason for which is yet unknown.

Comparative cytogenetic survey of the giant bonytongue Arapaima fish (Osteoglossiformes: Arapaimidae), across different Amazonian and Tocantins/Araguaia River basins

The South American giant fishes of the genus Arapaima, commonly known as pirarucu, are one of the most iconic among Osteoglossiformes. Previously cytogenetic studies have identified their karyotype characteristics; however, characterization of cytotaxonomic differentiation across their distribution range remains unknown. In this study, we compared chromosomal characteristics using conventional and molecular cytogenetic protocols in pirarucu populations from the Amazon and Tocantins-Araguaia river basins to verify if there is differentiation among representatives of this genus. Our data revealed that individuals from all populations present the same diploid chromosome number 2n=56 and karyotype composed of 14 pairs of meta- to submetacentric and 14 pairs of subtelo- to acrocentric chromosomes. The minor and major rDNA sites are in separate chromosomal pairs, in which major rDNA sites corresponds to large heterochromatic blocks. Comparative genomic hybridizations (CGH) showed that the genome of these populations shared a great portion of repetitive elements, due to a lack of substantial specific signals. Our comparative cytogenetic data analysis of pirarucu suggested that, although significant genetic differences occur among populations, their general karyotype patterns remain conserved.(AU)

Os peixes gigantes da América do Sul do gêneroArapaima, comumente conhecidos como pirarucus, são um dos mais icônicos de Osteoglossiformes. Estudos citogenéticos prévios identificaram suas características cariotípicas, entretanto a caracterização da diferenciação citotaxonômica através de suas distribuições geográficas ainda são desconhecidas. Nesse estudo, nós comparamos características cromossômicas utilizando técnicas de citogenética clássica e molecular em populações das bacias dos rios Amazonas e Tocantins-Araguaia, a fim de verificar se há alguma diferenciação entre representantes desse gênero. Nossos dados revelaram que indivíduos de todas as populações apresentam número diploide de 2n=56 cromossomos e que seus cariótipos são compostos de 14 pares de cromossomos meta- e submetacêntricos e 14 pares de subtelo- e acrocêntricos. Os sítios maiores e menores de rDNA estão localizados em pares cromossômicos separados, onde os sítios maiores de rDNA correspondem a grandes blocos heterocromáticos. Hibridizações genômicas comparativas (CGH) mostraram que o genoma dos espécimes dessas populações é amplamente compartilhado, devido à falta de sinais substanciais específicos. Nossos dados de citogenética comparativa do pirarucu sugerem que embora diferenças genéticas significativas ocorram entre populações, os padrões cariotípicos gerais se mantêm conservados.(AU)

Cholangioscopy-guided steroid injection for refractory post liver transplant anastomotic strictures: a rescue case series.

BACKGROUND AND AIMS: Post liver transplant biliary anastomotic strictures have traditionally been treated with balloon dilation and multiple plastic stents. Fully covered self-expandable metallic stents may be used as an initial alternative or after multiple plastic stents failure. Refractory strictures can occur in 10-22% and require revisional surgery. Alternatively, cholangioscopy allows direct visualization and therapeutic approaches. We aimed to assess the feasibility, safety, and efficacy of balloon dilation combined with cholangioscopy-guided steroid injection for the treatment of refractory anastomotic biliary strictures. METHODS: Three post-orthotopic liver transplant patients who failed standard treatment of their biliary anastomotic strictures underwent endoscopic retrograde cholangiopancreatography with balloon dilation followed by cholangioscopy-guided steroid injection at a tertiary care center. Patients had follow-up with images and laboratorial tests to evaluate for residual stricture. RESULTS: Technical success of balloon dilation + cholangioscopy-guided steroid injection was achieved in all patients. Cholangioscopy permitted accurate evaluation of bile ducts and precise localization for steroid injection. No adverse events occurred. Mean follow-up was 26 months. Two patients are stent free and remain well in follow-up, with no signs of biliary obstruction. No further therapeutic endoscopic procedures or revisional surgery were required. One patient did not respond to balloon dilation + cholangioscopy-guided steroid injection after 11 months of follow-up and required repeat balloon dilation of new strictures above the anastomosis. CONCLUSION: Cholangioscopy-guided steroid injection combined with balloon dilation in the treatment of refractory post liver transplant strictures is feasible and safe. This method may be used as a rescue alternative before surgical approach. Randomized controlled trials comparing balloon dilation + cholangioscopy-guided steroid injection to fully covered self-expandable metallic stents are needed to determine the role of this treatment for anastomotic biliary strictures.

Severe yellow fever in Brazil: clinical characteristics and management.

BACKGROUND: Little is known about clinical characteristics and management of severe yellow fever as previous yellow fever epidemics often occurred in times or areas with little access to intensive care units (ICU). We aim to describe the clinical characteristics of severe yellow fever cases requiring admission to the ICU during the 2018 yellow fever outbreak in São Paulo, Brazil. Furthermore, we report on preliminary lessons learnt regarding clinical management of severe yellow fever. METHODS: Retrospective descriptive cohort study. Demographic data, laboratory test results on admission, clinical follow-up, and clinical outcomes were evaluated. RESULTS: From 10 January to 11 March 2018, 79 patients with laboratory confirmed yellow fever were admitted to the ICU in a tertiary hospital in Sao Paolo because of rapid clinical deterioration. On admission, the median AST was 7,000 IU/L, ALT 3,936 IU/L, total bilirubin 5.3 ml/dL, platelet 74 × 103/mm3, INR 2.24 and factor V 37%. Seizures occurred in 24% of patients, even without substantial intracranial hypertension. The high frequency of pancreatitis and rapidly progressive severe metabolic acidosis were notable findings. 73% of patients required renal replacement therapy. The in-hospital fatality rate was 67%. Patients with diabetes mellitus had a higher case fatality rate (CFR) of 80%, while patients without diabetes had a CFR of 65%. Leading causes of death were severe gastrointestinal bleeding, epileptic status, severe metabolic acidosis, necrohemorrhagic pancreatitis, and multi-organ failure. CONCLUSIONS: Severe yellow fever is associated with a high CFR. The following management lessons were learnt: Anticonvulsant drugs in patients with any symptoms of hepatic encephalopathy or arterial ammonia levels >70 µmol/L was commenced which reduced the frequency of seizures from 28% to 17%. Other new therapy strategies included early institution of plasma exchange. Due to the high frequency of gastric bleeding, therapeutic doses of intravenous proton pump inhibitors should be administered.

Hepatocellular carcinoma recurrence after liver transplantation in a Brazilian multicenter study: clinical profile and prognostic factors of survival.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. PATIENTS AND METHODS: We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. RESULTS: OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified α-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. CONCLUSION: In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis.