Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Evoluzione dei frutti: i principali meccanismi molecolari alla base dello sviluppo dei frutti carnosi sono apparsi già nelle Gimnosperme

The fruit is a typical Angiosperm structure that derives from an ovary after fertilisation. It has greatly contributed to the evolutionary success of Angiosperms because of the fundamental role played in the dispersal of seeds. Gymnosperms produce seeds like Angiosperms but, unlike the latter, they do not make flowers, therefore they cannot develop fruit proper. However, in all living Gymnosperm taxa (Cycadales, Ginkgoales, Coniferales and Gnetales) species can be found that produce seeds surrounded by fleshy structures. The latter would not be a real fruit because they are not originated from ovaries which are present only in flowers. However, from a functional point of view these structures behave like real fruits because they facilitate the dispersal of seeds. The aim of this work is to study some of the molecular mechanisms involved in the development and ripening of fleshy structures in two Gymnosperms: Ginkgo biloba and Taxus baccata. They represent two Gymnosperms whose seeds are surrounded by fleshy structures that have different origins. In ginkgo it is the external integument of the seed that grows and becomes fleshy, while in yew the fleshy aril develops de novo from the peduncle at the base of the ovule. Regarding development, MADS-box genes belonging to different groups (i.e. AGL6 and TM8) were studied. The expression pattern of these genes was determined for both species in several tissues, with particular attention for the pulp at different stages of development. Results indicate a possible role for the above genes during the formation and ripening of both ginkgo and yew “fruits”. Interestingly, a previous study had demonstrated that another MADS-box gene (i.e. AGAMOUS) was involved in fruit development and ripening in the same species (Lovisetto, 2007). These results suggest that similar genes have been recruited for the development of fleshy fruits in Angiosperms and Gymnosperms. In order to investigate the molecular aspects of the ripening syndrome, several genes involved in the softening process, in the change of color, in the synthesis and perception of ethylene were studied both in ginkgo and yew. Results indicate a strong similarity between aril and Angiosperm fruits as regards the ripening process even though ethylene does not appear to be produced by a system 2 pathway as occurs in the truly climacteric fruits. Based on the function performed and the molecular characteristics studied in this work, the fleshy structures surrounding the Gymnosperm seeds can be defined fruits. Thus, the “fruit” function seems to have developed in parallel with the seed and to have pre-dated the appearance of the flower.Il frutto, inteso come struttura derivata dall’ovario in seguito ad un evento di fecondazione, è esclusivo delle Angiosperme. Esso ha contribuito enormemente al successo evolutivo di queste piante dato il ruolo fondamentale che svolge nel processo di dispersione dei semi. Tuttavia, anche le Gimnosperme producono i semi, anche se a differenza delle Angiosperme non fanno fiori. In tutti i principali taxa di Gimnosperme viventi (Cycadales, Ginkgoales, Coniferales e Gnetales) sono presenti specie che producono semi circondati da strutture carnose che non sarebbero veri frutti perché non sono originate da ovari. Però, da un punto di vista funzionale, queste strutture sono da considerarsi come dei frutti poiché, come nel caso dei frutti delle Angiosperme, anch'esse facilitano la dispersione dei semi. In questo lavoro sono stati studiati alcuni meccanismi molecolari coinvolti nello sviluppo e nella maturazione dei “frutti” di due Gimnosperme: Ginkgo biloba e Taxus baccata. Queste due specie sono state scelte perché rappresentano due modelli sperimentali diversi. Nel caso del ginkgo è il tegumento esterno del seme che diventa carnoso e si trasforma in frutto, mentre nel caso del tasso la struttura carnosa è costituita da un arillo che si forma ex novo dalla base dell'ovulo. Per quanto riguarda lo sviluppo, in entrambe le specie, sono stati studiati geni di tipo MADS-box appartenenti a due gruppi diversi: AGL6 e TM8. Il pattern di espressione di questi geni è stato analizzato per entrambe le specie con particolare attenzione per la polpa a diverso stadio di sviluppo. Da queste analisi è emerso come questi geni siano espressi durante la formazione e la maturazione sia dell’arillo di tasso che della polpa di ginkgo. Inoltre, visto che anche il gene AGAMOUS partecipa allo sviluppo e alla maturazione sia del “frutto” di tasso che del “frutto” di ginkgo (Lovisetto, 2007), si può concludere che geni regolativi simili a quelli espressi nei frutti veri delle Angiosperme sono implicati anche nello sviluppo delle strutture carnose che circondano i semi di tasso e di ginkgo. Poiché nulla era noto a livello molecolare riguardo alla sindrome di maturazione dell’arillo di tasso e della polpa di ginkgo, sono stati isolati e analizzati anche alcuni geni che nelle Angiosperme codificano per enzimi coinvolti nei processi di rammollimento, cambiamento di colore e sintesi e percezione di etilene. I risultati hanno mostrato come nella maturazione dell’arillo di tasso siano coinvolti lo stesso tipo di geni che operano nella maturazione dei veri frutti delle Angiosperme, anche se nel caso dell’etilene ci sono delle differenze rispetto a quanto avviene nei frutti climaterici. Invece, nel caso del ginkgo sembra che la polpa vada incontro a un processo di senescenza in generale più che a un processo di maturazione vera e propria. In conclusione, i risultati di questo lavoro suggeriscono che nel corso dell'evoluzione la funzione “frutto” si sia evoluta assieme al seme e abbia quindi preceduto la comparsa dei fiori

Characterization of an AGAMOUS gene expressed throughout development of the fleshy fruit-like structure produced by Ginkgo biloba around its seeds

Background: The involvement of MADS-box genes of the AGAMOUS lineage in the formation of both flowers and fruits has been studied in detail in Angiosperms. AGAMOUS genes are expressed also in the reproductive structures of Gymnosperms, yet the demonstration of their role has been problematic because Gymnosperms are woody plants difficult to manipulate for physiological and genetic studies. Recently, it was shown that in the gymnosperm Ginkgo biloba an AGAMOUS gene was expressed throughout development and ripening of the fleshy fruit-like structures produced by this species around its seeds. Such fleshy structures are evolutionarily very important because they favor the dispersal of seeds through endozoochory. In this work a characterization of the Ginkgo gene was carried out by over-expressing it in tomato. Results: In tomato plants ectopically expressing the Ginkgo AGAMOUS gene a macroscopic anomaly was observed only in the flower sepals. While the wild type sepals had a leaf-like appearance, the transgenic ones appeared connately adjoined at their proximal extremity and, concomitant with the development and ripening of the fruit, they became thicker and acquired a yellowish-orange color, thus indicating that they had undergone a homeotic transformation into carpel-like structures. Molecular analyses of several genes associated with either the control of ripening or the ripening syndrome in tomato fruits confirmed that the transgenic sepals behaved like ectopic fruits that could undergo some ripening, although the red color typical of the ripe tomato fruit was never achieved. Conclusions: The ectopic expression of the Ginkgo AGAMOUS gene in tomato caused the homeotic transformation of the transgenic sepals into carpel-like structures, and this showed that the gymnosperm gene has a genuine C function. In parallel with the ripening of fruits the related transgenic sepals became fleshy fruit-like structures that also underwent some ripening and such a result indicates that this C function gene might be involved, together with other gens, also in the development of the Ginkgo fruit-like structures. It seems thus strengthened the hypothesis that AGAMOUS MADS-box genes were recruited already in Gymnosperms for the development of the fleshy fruit habit which is evolutionarily so important for the dispersal of seed

Gymnosperm B-sister genes may be involved in ovule/seed development and, in some species only, in the growth of fleshy fruit-like structures.

\u2020 Background and Aims The evolution of seeds together with the mechanisms related to their dispersal into the environmentrepresented a turning point in the evolution of plants. Seeds are produced by gymnosperms and angiospermsbut only the latter have an ovary to be transformed into a fruit. Yet some gymnosperms produce fleshystructures attractive to animals, thus behaving like fruits from a functional point of view. The aim of this work isto increase our knowledge of possible mechanisms common to the development of both gymnosperm and angiospermfruits.\u2020 Methods B-sister genes from two gymnosperms (Ginkgo biloba and Taxus baccata) were isolated and studied.The Ginkgo gene was also functionally characterized by ectopically expressing it in tobacco.\u2020 Key Results In Ginkgo the fleshy structure derives from the outer seed integument and the B-sister gene is involvedin its growth. In Taxus the fleshy structure is formed de novo as an outgrowth of the ovule peduncle, and the B-sistergene is not involved in this growth. In transgenic tobacco the Ginkgo gene has a positive role in tissue growth andconfirms its importance in ovule/seed development.\u2020Conclusions This study suggests that B-sister genes have a main function in ovule/seed development and a subsidiaryrole in the formation of fleshy fruit-like structureswhenthe latter have an ovular origin, as occurs in Ginkgo. Thus,the \u2018fruit function\u2019 of B-sister genes is quite old, already being present in Gymnosperms as ancient as Ginkgoales, andis also present in Angiosperms where a B-sister gene has been shown to be involved in the formation of theArabidopsis fruit

Molecular analyses of MADS-box genes trace back to Gymnosperms the invention of fleshy fruits

Botanical fruits derive from ovaries and their most important function is to favor seed dispersal. Fleshy fruits do so byattracting frugivorous animals that disperse seeds together with their own excrements (endozoochory). Gymnospermsmake seeds but have no ovaries to be transformed into fruits. Many species surround their seeds with fleshy structures anduse endozoochory to disperse them. Such structures are functionally fruits and can derive from different anatomical parts.Ginkgo biloba and Taxus baccata fruit-like structures differ in their anatomical origin since the outer seed integumentbecomes fleshy in Ginkgo, whereas in Taxus, the fleshy aril is formed de novo. The ripening characteristics are different,with Ginkgo more rudimentary and Taxus more similar to angiosperm fruits. MADS-box genes are known to be necessaryfor the formation of flowers and fruits in Angiosperms but also for making both male and female reproductive structuresin Gymnosperms. Here, a series of different MADS-box genes have been shown for the first time to be involved also in theformation of gymnosperm fruit-like structures. Apparently, the same gene types have been recruited in phylogeneticallydistant species to make fleshy structures that also have different anatomical origins. This finding indicates that the mainmolecular networks operating in the development of fleshy fruits have independently appeared in distantly relatedGymnosperm taxa. Hence, the appearance of the seed habit and the accompanying necessity of seed dispersal has led tothe invention of the fruit habit that thus seems to have appeared independently of the presence of flowers

Characterization of TM8, a MADS-box gene expressed in tomato flowers

Background.The identity of flower organs is specified by various MIKC MADS-box transcription factors which act in a combinatorial manner. TM8 is a MADS-box gene that was isolated from the floral meristem of a tomato mutant more than twenty years ago, but is still poorly known from a functional point of view in spite of being present in both Angiosperms and Gymnosperms, with some species harbouring more than one copy of the gene. This study reports a characterization of TM8 that was carried out in transgenic tomato plants with altered expression of the gene. Results. Tomato plants over-expressing either TM8 or a chimeric repressor form of the gene (TM8:SRDX) were prepared. In the TM8 up-regulated plants it was possible to observe aberrant stamens with poorly viable pollen and altered expression of several floral identity genes, among them B-, C- and E-function ones, while no apparent morphological modifications were visible in the other whorls. Oblong ovaries and fruits, that were also parthenocarpic, were obtained in the plants expressing theTM8:SRDX repressor gene. Such ovaries showed modified expression of various carpel-related genes. No apparent modifications could be seen in the other flower whorls. The latter plants had also epinastic leaves and malformed flower abscission zones. By using yeast two hybrid assays it was possible to show that TM8 was able to interact in yeast with MACROCALIX. Conclusions. The impact of the ectopically altered TM8 expression on the reproductive structures suggests that this gene plays some role in the development of the tomato flower. MACROCALYX, a putative A-function MADS-box gene, was expressed in all the four whorls of fully developed flowers, and showed quantitative variations that were opposite to those of TM8 in the aberrant stamens and ovaries. Since the TM8 protein interacted in vitro only with A-function MADS-box proteins like the tomato MACROCALYX, it seems that for the correct differentiation of the tomato reproductive structures possible interactions between TM8 and MACROCALYX proteins might be important

Characterization of a bZIP gene highly expressed during ripening of the peach fruit

A ripening specific bZIP gene of peach was studied by ectopically expressing it in tomato. Two lines, witheither a mild or a strong phenotype, respectively, were analyzed in detail. Transgenic fruit morphologywas normal, yet the time spent to proceed through the various ripening stages was longer compared towild type. In agreement with this finding the transgenic berries produced less ethylene, and also had amodified expression of some ripening-related genes that was particularly evident in berries with a strongphenotype. In particular, in the latter fruits polygalacturonase and lipoxygenase genes, but also genescoding for transcription factors (TFs) important for tomato ripening (i.e. TAGL1, CNR, APETALA2a, NOR) didnot show the expected decreased expression in the red berries. As regards the RIN gene, its expressioncontinued to increase in both mild and strong lines, and this is in agreement with the dilated ripeningtimes. Interestingly, a metabolomic analysis of berries at various stages of ripening showed that thelonger time spent by the transgenic berries to proceed from a stage to another was not due to a slackenedmetabolism. In fact, the differences in amount of stage-specific marker metabolites indicated that thetransgenic berries had a very active metabolism. Therefore, the dilated ripening and the enhancedmetabolism of the berries over-expressing the bZIP gene suggest that such gene might regulate ripeningby acting as a pacemaker for some of the ripening metabolic pathways