Impact of the COVID-19 Pandemic on Enhanced Recovery After Surgery (ERAS) Application and Outcomes: Analysis in the "Lazio Network" Database.

BACKGROUND: The aim of this study was to investigate how the COVID-19 pandemic influenced ERAS program application in colorectal surgery across hospitals in the Lazio region (central district in Italy) participating in the "Lazio Network" project. METHODS: A multi-institutional database was constructed. All patients included in this study underwent elective colorectal surgery for both malignant and benign disease between January 2019 and December 2020. Emergency procedures were excluded. The population was divided into 2 groups: a pre-COVID-19 group (PG) of patients operated on between February and December 2019 and a COVID-19 group (CG) of patients operated on between February and December 2020, during the first 2 waves of the pandemic in Italy. RESULTS: The groups included 622 patients in the PG and 615 in the CG treated in 8 hospitals of the network. The mean number of items applied was higher in the PG (65.6% vs. 56.6%, p < 0.001) in terms of preoperative items (64.2% vs. 50.7%, p < 0.001), intraoperative items (65.0% vs. 53.3%, p < 0.001), and postoperative items (68.8% vs. 63.2%, p < 0.001). Postoperative recovery was faster in the PG, with a shorter time to first flatus, first stool, autonomous mobilization and discharge (6.82 days vs. 7.43 days, p = 0.021). Postoperative complications, mortality and reoperations were similar among the groups. CONCLUSIONS: The COVID-19 pandemic had a negative impact on the application of ERAS in the centers of the "Lazio Network" study group, with a reduction in adherence to the ERAS protocol in terms of preoperative, intraoperative and postoperative items. In addition, in the CG, the patients had worse postoperative outcomes with respect to recovery and discharge.

Enhanced recovery after surgery (ERAS) program in octogenarian patients: a propensity score matching analysis on the "Lazio Network" database.

PURPOSE: The aim of this study was to evaluate the safety and compliance with the enhanced recovery after surgery (ERAS) protocol in octogenarian patients undergoing colorectal surgery in 12 Italian high-volume centers. METHODS: A retrospective analysis was conducted in a consecutive series of patients who underwent elective colorectal surgery between 2016 and 2018. Patients were grouped by age (≥ 80 years vs < 80 years), propensity score matching (PSM) analysis was performed, and the groups were compared regarding clinical outcomes and the mean number of ERAS items applied. RESULTS: Out of 1646 patients identified, 310 were octogenarians. PSM identified 2 cohorts of 125 patients for the comparison of postoperative outcomes and ERAS compliance. The 2 groups were homogeneous regarding the clinical variables and mean number of ERAS items applied (11.3 vs 11.9, p-ns); however, the application of intraoperative items was greater in nonelderly patients (p 0.004). The functional recovery was similar between the two groups, as were the rates of postoperative severe complications and 30-day mortality rate. Elderly patients had more overall complications. Furthermore, the mean hospital stay was higher in the elderly group (p 0.027). Multivariable analyses documented that postoperative stay was inversely correlated with the number of ERAS items applied (p < 0.0001), whereas age ≥ 80 years significantly correlated with the overall complication rate (p 0.0419). CONCLUSION: The ERAS protocol is safe in octogenarian patients, with similar levels of compliance and surgical outcomes. However, octogenarian patients have a higher rate of overall complications and a longer hospital stay than do younger patients.

RAS mutations in human cancers: Roles in precision medicine.

Ras proteins play a crucial role as a central component of the cellular networks controlling a variety of signaling pathways that regulate growth, proliferation, survival, differentiation, adhesion, cytoskeletal rearrangements and motility of a cell. Almost, 4 decades passed since Ras research was started and ras genes were originally discovered as retroviral oncogenes. Later on, mutations of the human RAS genes were linked to tumorigenesis. Genetic analyses found that RAS is one of the most deregulated oncogenes in human cancers. In this review, we summarize the pioneering works which allowed the discovery of RAS oncogenes, the finding of frequent mutations of RAS in various human cancers, the role of these mutations in tumorigenesis and mutation-activated signaling networks. We further describe the importance of RAS mutations in personalized or precision medicine particularly in molecular targeted therapy, as well as their use as diagnostic and prognostic markers as therapeutic determinants in human cancers.

Adjustment of photosynthetic activity to drought and fluctuating light in wheat.

Drought is a major cause of losses in crop yield. Under field conditions, plants exposed to drought are usually also experiencing rapid changes in light intensity. Accordingly, plants need to acclimate to both, drought and light stress. Two crucial mechanisms in plant acclimation to changes in light conditions comprise thylakoid protein phosphorylation and dissipation of light energy as heat by non-photochemical quenching (NPQ). Here, we analyzed the acclimation efficacy of two different wheat varieties, by applying fluctuating light for analysis of plants, which had been subjected to a slowly developing drought stress as it usually occurs in the field. This novel approach allowed us to distinguish four drought phases, which are critical for grain yield, and to discover acclimatory responses which are independent of photodamage. In short-term, under fluctuating light, the slowdown of NPQ relaxation adjusts the photosynthetic activity to the reduced metabolic capacity. In long-term, the photosynthetic machinery acquires a drought-specific configuration by changing the PSII-LHCII phosphorylation pattern together with protein stoichiometry. Therefore, the fine-tuning of NPQ relaxation and PSII-LHCII phosphorylation pattern represent promising traits for future crop breeding strategies.

Impact of implementation of the ERAS program in colorectal surgery: a multi-center study based on the "Lazio Network" collective database.

BACKGROUND: ERAS implementation improved outcomes in patients undergoing colorectal surgery. The process of incorporating this pathway in clinical practice may be challenging. This observational study investigated the impact of systematic ERAS implementation on surgical outcomes in patients undergoing colorectal resections in a regional network of 10 institutions. METHODS: Implementation of ERAS pathway was designed using regular audits and a common protocol. All patients undergoing elective colorectal surgery between 2016 and 2017 were considered eligible. A collective database including 18 ERAS items, clinical and surgical data, and outcomes was designed. Univariate and multivariate analyses were performed for the following outcomes: morbidity, anastomotic leak, reinterventions, hospital stay, and readmissions. RESULTS: A total of 827 patients were included, and a mean of 11.3 ERAS items applied/patient was reported. Logistic regression indicated that an increased number of ERAS items applied reduced overall and severe morbidity (OR 0.86 and 0.87, respectively 95%CI 0.8197-0.9202 and 95%CI 0.7821-0.9603), hospitalization (OR 0.53 95%CI 0.4917-0.5845) and reinterventions (OR 0.84 95%CI 0.7536-0.9518) in the entire series. The same results were obtained for a prolonged hospitalization differentiating right-sided (OR 0.48 95%CI 0.4036-0.5801), left-sided (OR 0.48 95%CI 0.3984-0.5815), and rectal resections (OR 0.46 95%CI 0.3753-0.5851). An inverse correlation was found between the application of ERAS items and morbidity in right-sided and rectal procedures (OR 0.89 and 0.84, respectively 95%CI 0.7976-0.9773 and 95%CI 0.7418-0.9634). CONCLUSIONS: Systematic implementation of the ERAS pathway using multi-institutional audits can increase protocol adherence and improve surgical outcomes in patients undergoing colorectal surgery.

Ruta graveolens water extract inhibits cell-cell network formation in human umbilical endothelial cells via MEK-ERK1/2 pathway.

Angiogenesis is a process encompassing several steps such as endothelial cells proliferation, differentiation and migration to form a vascular network, involving different signal transduction pathways. Among these, ERK1/2 signaling mediates VEGF-dependent signaling pathway. Here we report that the water extract of Ruta graveolens (RGWE), widely known as a medicinal plant, is able to impair in a dose-dependent manner, cell network formation without affecting cell viability. Biochemical analysis showed that the major component of RGWE is rutin, unable to reproduce RGWE effect. We found that RGWE inhibits ERK1/2 phosphorylation and that this event is crucial in cell network formation since the transfection of HUVEC with a constitutively active MEK (caMEK), the ERK1/2 activator, induces a robust cell network formation as compared to untransfected and/or mock transfected cells and, more importantly, caMEK transfected cells became unresponsive to RGWE. Moreover, RGWE inhibits VEGF and nestin gene expression, necessary for vessel formation, and the caMEK transfection induces their higher expression. In conclusion, we report that RGWE is able to significantly impair vessels network formation without affecting cell viability, preventing ERK1/2 activation and, in turn, down-regulating VEGF and nestin expression. These findings point to RGWE as a potential therapeutic tool capable to interfere with pathologic angiogenesis.

Robotic pelvic dissection as surgical treatment of complicated diverticulitis in elective settings: a comparative study with fully laparoscopic procedure.

BACKGROUND: Recently, minimally invasive treatment of complicated sigmoid diverticulitis is becoming a valid alternative to standard procedures. Robotic approach may be useful to allow more precise dissection in arduous pelvic dissection as in complicated diverticulitis. The aim of this study is to investigate effectiveness, potential benefits and short-term outcomes of robotic-assisted laparoscopic surgical resection, compared with fully laparoscopic resection in complicated diverticulitis. METHODS: Between January 2009 and December 2017, 156 consecutive patients with history of complicated diverticular disease were referred to our Department of General, Mininvasive and Robotic Surgery. All patients underwent elective colonic resections performed by the same colorectal surgeon and followed a perioperative ERAS program. Demographic and clinical features, surgical data, postoperative data, 30-day morbidity and mortality, VAS for surgeon's compliance were evaluated. RESULTS: One hundred and fifty-six consecutive patients underwent elective colonic resection: 92 fully laparoscopic (FL) colorectal resections and 64 procedures with robotic hybrid approach (RHA). Conversion rate was none in the RHA group versus 6.5% in the FL group, because of poor vision due to bowel distension, inflammatory pseudotumor and peritoneal adhesions. No 30-day mortality was observed. Mean operative time was 167.5 ± 54.4 min (80-420) in the FL group and 172.5 ± 55.64 min (110-325) in the RHA group (p 0.079), mean intraoperative blood loss was 144.6 ± 40.6 ml (40-200) with the FL technique and 138.4 ± 28.3 ml (20-185) with the RHA (p 0.295). Mean hospital stay for FL was 5 ± 4.1 days (range 3-45) and 5 ± 2.7 days (range 3-20) for RHA (p 0.974). Overall postoperative morbidity rate was 21.6% in the FL group and 12.3% in the RHA (p 0.067). Major postoperative morbidity (Clavien-Dindo 3 and 4) represented 13% and 4.6%, respectively (p 0.091). VAS for surgeon's compliance revealed a better performance in the robotic arm (p 0.059). CONCLUSIONS: This preliminary study highlights the potential benefits of robotic-assisted laparoscopy in colorectal resections for complicated diverticular disease in terms of surgical efficacy, postoperative morbidity and better surgeon's compliance.

Major vessel sealing in laparoscopic surgery for colorectal cancer: a single-center experience with 759 patients.

BACKGROUND: Efficient hemostatic techniques are essential in laparoscopic surgery for ideal intraoperative and postoperative results. A variety of advanced devices are available for the sealing of major vascular structures. The aim of this study is to assess effectiveness and safety of major vessel sealing with a radiofrequency device during laparoscopic colorectal resections for cancer based on the experience of a single hospital. METHODS: Early outcomes of a consecutive series of patients who received elective laparoscopic colorectal resections for cancer over a 10-year period (January 2008-September 2017) are analyzed. In all procedures, the Ligasure® electrothermal bipolar device was used for the closure of the major colonic vessels and the dissection of all the structures. No other products such clips, staplers, hemostatic products, or other devices were used. RESULTS: Seven-hundred fifty-nine procedures were performed in laparoscopy: 179 rectal resections, 247 sigmoidectomies and left hemicolectomies, 240 right hemicolectomies, 33 resections of the splenic flexure, 35 transverse colonic resections, and 25 other procedures. In 39 cases, the laparoscopic procedure was converted to open surgery, and in these cases, vessel sealing was also achieved with the radiofrequency device alone. Vessel dissection and sealing was realized in all cases without any intraoperative or postoperative bleeding. No reoperations for bleeding from major vessels were performed in any patients. One case of reoperation was recorded postoperatively, at 3 h after right hemicolectomy, due to a small bleeding from the fat of the transverse colon stump. CONCLUSIONS: The use of Ligasure® radiofrequency device for sealing and dividing the major colonic vessels is safe, fast, and effective during laparoscopic colorectal resections.

Arabidopsis PIAL1 and 2 promote SUMO chain formation as E4-type SUMO ligases and are involved in stress responses and sulfur metabolism.

The Arabidopsis thaliana genes PROTEIN INHIBITOR OF ACTIVATED STAT LIKE1 (PIAL1) and PIAL2 encode proteins with SP-RING domains, which occur in many ligases of the small ubiquitin-related modifier (SUMO) conjugation pathway. We show that PIAL1 and PIAL2 function as SUMO ligases capable of SUMO chain formation and require the SUMO-modified SUMO-conjugating enzyme SCE1 for optimal activity. Mutant analysis indicates a role for PIAL1 and 2 in salt stress and osmotic stress responses, whereas under standard conditions, the mutants show close to normal growth. Mutations in PIAL1 and 2 also lead to altered sulfur metabolism. We propose that, together with SUMO chain binding ubiquitin ligases, these enzymes establish a pathway for proteolytic removal of sumoylation substrates.

Light-harvesting II antenna trimers connect energetically the entire photosynthetic machinery - including both photosystems II and I.

In plant chloroplasts, the two photosystems (PSII and PSI) are enriched in different thylakoid domains and, according to the established view, are regarded as energetically segregated from each other. A specific fraction of the light harvesting complex II (LHCII) has been postulated to get phosphorylated by the STN7 kinase and subsequently to migrate from PSII to PSI as part of a process called 'state transition'. Nevertheless, the thylakoid membrane incorporates a large excess of LHCII not present in the isolatable PSII-LHCII and PSI-LHCII complexes. Moreover, LHCII phosphorylation is not limited to a specific LHCII pool and "state 2" condition, but is found in all thylakoid domains in any constant light condition. Here, using a targeted solubilization of pigment-protein complexes from different thylakoid domains, we demonstrate that even a minor detachment of LHCII leads to markedly increased fluorescence emission from LHCII and PSII both in grana core and non-appressed thylakoid membranes and the effect of the detergent to detach LHCII is enhanced in the absence of LHCII phosphorylation. These findings provide evidence that PSII and PSI are energy traps embedded in the same energetically connected LHCII lake. In the lake, PSI and LHCII are energetically connected even in the absence of LHCII phosphorylation, yet the phosphorylation enhances the interaction required for efficient energy transfer to PSI in the grana margin regions.

Light acclimation involves dynamic re-organization of the pigment-protein megacomplexes in non-appressed thylakoid domains.

Thylakoid energy metabolism is crucial for plant growth, development and acclimation. Non-appressed thylakoids harbor several high molecular mass pigment-protein megacomplexes that have flexible compositions depending upon the environmental cues. This composition is important for dynamic energy balancing in photosystems (PS) I and II. We analysed the megacomplexes of Arabidopsis wild type (WT) plants and of several thylakoid regulatory mutants. The stn7 mutant, which is defective in phosphorylation of the light-harvesting complex (LHC) II, possessed a megacomplex composition that was strikingly different from that of the WT. Of the nine megacomplexes in total for the non-appressed thylakoids, the largest megacomplex in particular was less abundant in the stn7 mutant under standard growth conditions. This megacomplex contains both PSI and PSII and was recently shown to allow energy spillover between PSII and PSI (Nat. Commun., 6, 2015, 6675). The dynamics of the megacomplex composition was addressed by exposing plants to different light conditions prior to thylakoid isolation. The megacomplex pattern in the WT was highly dynamic. Under darkness or far red light it showed low levels of LHCII phosphorylation and resembled the stn7 pattern; under low light, which triggers LHCII phosphorylation, it resembled that of the tap38/pph1 phosphatase mutant. In contrast, solubilization of the entire thylakoid network with dodecyl maltoside, which efficiently solubilizes pigment-protein complexes from all thylakoid compartments, revealed that the pigment-protein composition remained stable despite the changing light conditions or mutations that affected LHCII (de)phosphorylation. We conclude that the composition of pigment-protein megacomplexes specifically in non-appressed thylakoids undergoes redox-dependent changes, thus facilitating maintenance of the excitation balance between the two photosystems upon changes in light conditions.

An evolutionary view on thylakoid protein phosphorylation uncovers novel phosphorylation hotspots with potential functional implications.

The regulation of photosynthetic light reactions by reversible protein phosphorylation is well established today, but functional studies have so far mostly been restricted to processes affecting light-harvesting complex II and the core proteins of photosystem II. Virtually no functional data are available on regulatory effects at the other photosynthetic complexes despite the identification of multiple phosphorylation sites. Therefore we summarize the available data from 50 published phospho-proteomics studies covering the main complexes involved in photosynthetic light reactions in the 'green lineage' (i.e. green algae and land plants) as well as its cyanobacterial counterparts. In addition, we performed an extensive orthologue search for the major photosynthetic thylakoid proteins in 41 sequenced genomes and generated sequence alignments to survey the phylogenetic distribution of phosphorylation sites and their evolutionary conservation from green algae to higher plants. We observed a number of uncharacterized phosphorylation hotspots at photosystem I and the ATP synthase with potential functional relevance as well as an unexpected divergence of phosphosites. Although technical limitations might account for a number of those differences, we think that many of these phosphosites have important functions. This is particularly important for mono- and dicot plants, where these sites might be involved in regulatory processes such as stress acclimation.

A Standardized Method of Isolating Adipose-Derived Stem Cells for Clinical Applications.

White adipose tissue is the most abundant and accessible source of stem cells in the adult human body. In this paper, we present a standardised and safe method of isolating and maximizing the number of adipose-derived stem cells (ASCs) from conventional liposuction for clinical applications, which was carried out through both mechanical (centrifuge) and enzymatic (collagenase) means. Isolated cells were characterized through flow cytometry assay. Gathered data showed a greater amount (9.06 × 10(5) ASCs from 100 mL of adipose tissue) of isolated ASCs compared to previous protocol, also with high (99%) cell vitality; the procedure we presented is easy and fast (80 minutes), allowing collecting a significative number of mesenchymal stem cells, which can be used for clinical purposes, such as wound healing.

PROTON GRADIENT REGULATION5 is essential for proper acclimation of Arabidopsis photosystem I to naturally and artificially fluctuating light conditions.

In nature, plants are challenged by constantly changing light conditions. To reveal the molecular mechanisms behind acclimation to sometimes drastic and frequent changes in light intensity, we grew Arabidopsis thaliana under fluctuating light conditions, in which the low light periods were repeatedly interrupted with high light peaks. Such conditions had only marginal effect on photosystem II but induced damage to photosystem I (PSI), the damage being most severe during the early developmental stages. We showed that PROTON GRADIENT REGULATION5 (PGR5)-dependent regulation of electron transfer and proton motive force is crucial for protection of PSI against photodamage, which occurred particularly during the high light phases of fluctuating light cycles. Contrary to PGR5, the NAD(P)H dehydrogenase complex, which mediates cyclic electron flow around PSI, did not contribute to acclimation of the photosynthetic apparatus, particularly PSI, to rapidly changing light intensities. Likewise, the Arabidopsis pgr5 mutant exhibited a significantly higher mortality rate compared with the wild type under outdoor field conditions. This shows not only that regulation of PSI under natural growth conditions is crucial but also the importance of PGR5 in PSI protection.

Multiple aspects of matrix stiffness in cancer progression.

The biophysical and biomechanical properties of the extracellular matrix (ECM) are crucial in the processes of cell differentiation and proliferation. However, it is unclear to what extent tumor cells are influenced by biomechanical and biophysical changes of the surrounding microenvironment and how this response varies between different tumor forms, and over the course of tumor progression. The entire ensemble of genes encoding the ECM associated proteins is called matrisome. In cancer, the ECM evolves to become highly dysregulated, rigid, and fibrotic, serving both pro-tumorigenic and anti-tumorigenic roles. Tumor desmoplasia is characterized by a dramatic increase of α-smooth muscle actin expressing fibroblast and the deposition of hard ECM containing collagen, fibronectin, proteoglycans, and hyaluronic acid and is common in many solid tumors. In this review, we described the role of inflammation and inflammatory cytokines, in desmoplastic matrix remodeling, tumor state transition driven by microenvironment forces and the signaling pathways in mechanotransduction as potential targeted therapies, focusing on the impact of qualitative and quantitative variations of the ECM on the regulation of tumor development, hypothesizing the presence of matrisome drivers, acting alongside the cell-intrinsic oncogenic drivers, in some stages of neoplastic progression and in some tumor contexts, such as pancreatic carcinoma, breast cancer, lung cancer and mesothelioma.

Electrochemotherapy in Kaposi's Sarcoma Patients: From the Gold Standard Strategy to Locally Advanced Cutaneous and Subcutaneous Lesions.

Electrochemotherapy (ECT) is one of the newest therapeutic strategies employed as a medical procedure for skin neoplasms' treatment, especially for classic Kaposi's sarcoma (CKS). The aim of this study was to demonstrate ECT clinical response and the local control of CKS disease. The primary endpoint was to value the worth and efficacy of this local therapy in CKS skin lesions' treatment. In total, 19 CKS patients were enrolled, 14 males and 5 females with median age at diagnosis of 72. Complete response (CR) has been gained in 12 patients after first ECT attempt; meanwhile, 3 and 4 out of 19 patients obtained a partial response (PR), so they underwent a second and third ECT treatment, respectively. Clinical response was evaluated during the entire timeframe of the follow-up, which ranged between 3 months and 4 years with a median of 18 months. The control of CKS skin lesions still represents a challenge for surgeons and oncologists. Nevertheless, according to this and other authors' recent experiences, ECT could be considered the gold standard strategy for early-stage patients, but at the same time it could be considered as a valid option in controlling Kaposi's sarcoma locally advanced lesions.

Management of acute diverticulitis in Stage 0-IIb: indications and risk factors for failure of conservative treatment in a series of 187 patients.

Left-sided acute diverticulitis in WSES Stage 0-IIb preferentially undergoes conservative management. However, there is limited understanding of the risk factors for failure of this approach. The aim of this study was to investigate the factors associated with the decision to perform conservative treatment as well as the predictors of its failure. We included patients with a diagnosis of WSES diverticulitis CT-driven classification Stage 0-IIb treated in the Emergency Surgery Unit of the Agostino Gemelli University Hospital Foundation between 2014 and 2020. The endpoints were the comparison between the characteristics and clinical outcomes of acute diverticulitis patients undergoing conservative versus operative treatment. We also identified predictors of conservative treatment failure. A set of multivariable backward logistic analyses were conducted for this purpose. The study included 187 patients. The choice for operative versus conservative treatment was associated with clinical presentation, older age, higher WSES grade, and previous conservative treatment. There were 21% who failed conservative treatment. Of those, major morbidity and mortality rates were 17.9% and 7.1%, respectively. A previously failed conservative treatment as well as a greater WSES grade and a lower hemoglobin value were significantly associated with failure of conservative treatment. WSES classification and hemoglobin value at admission were the best predictors of failure of conservative treatment. Patients failing conservative treatment had non-negligible morbidity and mortality. These results promote the consideration of a combined approach including baseline patients' characteristics, radiologic features, and laboratory biomarkers to predict conservative treatment failure and therefore optimize treatment of acute diverticulitis.

Steady-state phosphorylation of light-harvesting complex II proteins preserves photosystem I under fluctuating white light.

According to the "state transitions" theory, the light-harvesting complex II (LHCII) phosphorylation in plant chloroplasts is essential to adjust the relative absorption cross section of photosystem II (PSII) and PSI upon changes in light quality. The role of LHCII phosphorylation upon changes in light intensity is less thoroughly investigated, particularly when changes in light intensity are too fast to allow the phosphorylation/dephosphorylation processes to occur. Here, we demonstrate that the Arabidopsis (Arabidopsis thaliana) stn7 (for state transition7) mutant, devoid of the STN7 kinase and LHCII phosphorylation, shows a growth penalty only under fluctuating white light due to a low amount of PSI. Under constant growth light conditions, stn7 acquires chloroplast redox homeostasis by increasing the relative amount of PSI centers. Thus, in plant chloroplasts, the steady-state LHCII phosphorylation plays a major role in preserving PSI upon rapid fluctuations in white light intensity. Such protection of PSI results from LHCII phosphorylation-dependent equal distribution of excitation energy to both PSII and PSI from the shared LHCII antenna and occurs in cooperation with nonphotochemical quenching and the proton gradient regulation5-dependent control of electron flow, which are likewise strictly regulated by white light intensity. LHCII phosphorylation is concluded to function both as a stabilizer (in time scales of seconds to minutes) and a dynamic regulator (in time scales from tens of minutes to hours and days) of redox homeostasis in chloroplasts, subject to modifications by both environmental and metabolic cues. Exceeding the capacity of LHCII phosphorylation/dephosphorylation to balance the distribution of excitation energy between PSII and PSI results in readjustment of photosystem stoichiometry.

How to reduce the colorectal anastomotic leakage? The MIRACLe protocol experience in a cohort in a single high-volume centre.

This article reports the results of a novel perioperative treatment implementing the gut microbiota to prevent anastomotic fistula and leakage (AL) in patients undergoing laparoscopic colorectal resections for cancer and represents the continuation of our pilot study on 60 cases. A series of 131 patients underwent elective colorectal surgery at the S. Eugenio Hospital (Rome-Italy) between December 1, 2020, and November 30, 2022, and received a perioperative preparation following the Microbiota Implementation to Reduce Anastomotic Colorectal Leaks (MIRACLe) protocol comprising oral antibiotics, mechanical bowel preparation and perioperative probiotics. The results obtained in the MIRACLe group (MG) were compared to those registered in a Control group (CG) of 500 patients operated on between March 2015 and November 30, 2020, who received a standard ERAS protocol. Propensity score-matching (PSM) analysis was performed to overcome patients' selection bias. Patients were categorised according to perioperative preparation (MIRACLe protocol vs standard ERAS protocol) into two groups: 118 patients were in post-matched MIRACLe group (pmMG) and 356 were in post-matched Control group (pmCG). In the pmMG, only 2 anastomotic leaks were registered, and the incidence of AL was just 1.7% vs. 6.5% in the pmCG (p = 0.044). The incidence of surgical site infections (1.7% vs. 3.1%; p = 0.536), reoperations (0.8% vs. 4.2%; p = 0.136) and postoperative mortality (0% vs. 2.0%; p = 0.200) was lower in pmMG. Additionally, the postoperative outcomes were better: the times to first flatus, to first stool and to oral feeding were shorter (1 vs. 2, 2 vs. 3 and 2 vs. 3 days, respectively; p < 0.001). The postoperative recovery was faster, with a shorter time to discharge (5 vs. 6 days; p < 0.001). The MIRACLe protocol was confirmed to be safe and significantly able to reduce anastomotic leaks in patients receiving elective laparoscopic colorectal surgery for cancer.