Intraoperative endomanometric laparoscopic Nissen fundoplication improves postoperative outcomes in large sliding hiatus hernias with severe gastroesophageal reflux disease: a retrospective cohort study.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is the gold standard surgical intervention for gastroesophageal reflux disease (GERD). LNF can be followed by recurrent symptoms or complications affecting patient satisfaction. The aim of this study is to assess the value of the intraoperative endomanometric evaluation of esophagogastric competence and pressure combined with LNF in patients with large sliding hiatus hernia (>5 cm) with severe GERD (DeMeester score >100). MATERIALS AND METHODS: This is a retrospective, multicenter cohort study. Baseline characteristics, postoperative dysphagia and gas bloat syndrome, recurrent symptoms, and satisfaction were collected from a prospectively maintained database. Outcomes analyzed included recurrent reflux symptoms, postoperative side effects, and satisfaction with surgery. RESULTS: Three hundred sixty patients were stratified into endomanometric LNF (180 patients, LNF+) and LNF alone (180 patients, LNF). Recurrent heartburn (3.9 vs. 8.3%) and recurrent regurgitation (2.2 vs. 5%) showed a lower incidence in the LNF+ group ( P =0.012). Postoperative score III recurrent heartburn and score III regurgitations occurred in 0 vs. 3.3% and 0 vs. 2.8% cases in the LNF+ and LNF groups, respectively ( P =0.005). Postoperative persistent dysphagia and gas bloat syndrome occurred in 1.75 vs. 5.6% and 0 vs. 3.9% of patients ( P =0.001). Score III postoperative persistent dysphagia was 0 vs. 2.8% in the two groups ( P =0.007). There was no redo surgery for dysphagia after LNF+. Patient satisfaction at the end of the study was 93.3 vs. 86.7% in both cohorts, respectively ( P =0.05). CONCLUSIONS: Intraoperative high-resolution manometry and endoscopic were feasible in all patients, and the outcomes were favorable from an effectiveness and safety standpoint.

Source control in emergency general surgery: WSES, GAIS, SIS-E, SIS-A guidelines.

Intra-abdominal infections (IAI) are among the most common global healthcare challenges and they are usually precipitated by disruption to the gastrointestinal (GI) tract. Their successful management typically requires intensive resource utilization, and despite the best therapies, morbidity and mortality remain high. One of the main issues required to appropriately treat IAI that differs from the other etiologies of sepsis is the frequent requirement to provide physical source control. Fortunately, dramatic advances have been made in this aspect of treatment. Historically, source control was left to surgeons only. With new technologies non-surgical less invasive interventional procedures have been introduced. Alternatively, in addition to formal surgery open abdomen techniques have long been proposed as aiding source control in severe intra-abdominal sepsis. It is ironic that while a lack or even delay regarding source control clearly associates with death, it is a concept that remains poorly described. For example, no conclusive definition of source control technique or even adequacy has been universally accepted. Practically, source control involves a complex definition encompassing several factors including the causative event, source of infection bacteria, local bacterial flora, patient condition, and his/her eventual comorbidities. With greater understanding of the systemic pathobiology of sepsis and the profound implications of the human microbiome, adequate source control is no longer only a surgical issue but one that requires a multidisciplinary, multimodality approach. Thus, while any breach in the GI tract must be controlled, source control should also attempt to control the generation and propagation of the systemic biomediators and dysbiotic influences on the microbiome that perpetuate multi-system organ failure and death. Given these increased complexities, the present paper represents the current opinions and recommendations for future research of the World Society of Emergency Surgery, of the Global Alliance for Infections in Surgery of Surgical Infection Society Europe and Surgical Infection Society America regarding the concepts and operational adequacy of source control in intra-abdominal infections.

Differentiation of neurosphere after transplantation into the damaged spinal cord.

This study aimed to compare the differentiation and survival of human neural stem/progenitor cells of various origins in vitro and after transplantation into the injured spinal cord of laboratory animals. Rats with simulated spinal cord injury were transplanted with neurosphere cells obtained by directed differentiation of HUES6 cell lines. Fluorescence microscopy was used to visualize the obtained results. HUES6#1 and iPSC#1 neurospheres showed a wide range of markers associated with glial differentiation. The expression of the proliferation marker Ki67 did not exceed 25%, both in the lines of early and late neurospheres. Although neurospheres did not fully differentiate into astrocytes in vitro, they massively approached the GFAP+ astrocyte phenotype when exposed to the transplanted environment. PSC-derived neurospheres transplanted into the site of SM injury without additional growth factors showed only moderate survival, a significant degree of differentiation into astrocytes, and moderate differentiation into neurons. The difference in the survival and differentiation of HUES6#1 and iPSC#1 neurospheres, both in vitro and in vivo, can be explained by the difference in the regulatory behavior of signaling molecules corresponding to the source of origin of PSCs. Derivatives of human PSCs of various origins obtained according to the described differentiation protocol did not mature into astrocytic populations, nor did the glycogenic transition of PSC-derived NSCs occur in vitro. The study demonstrated the impact of the injured spinal cord microenvironment on the differentiation of transplanted HUES6#1 and iPSC#1 into astrocytes. The results showed that HUES6-derived neurospheres generated 90% of GFAP+ astrocytes and 5-10% of early neurons, while iPSC-derived neurospheres generated an average of 74% GFAP+ astrocytes and 5% of early neurons in vivo.

Physiological stress level and screening for malnutrition as preoperative predictors of postoperative complications in pancreatic surgery: a retrospective study.

BACKGROUND: Assessment of 'physiological stress levels' and 'nutritional status' before surgery is important for predicting complications and indirect interventions on the pancreas. The aim of this study was to determine neutrophil-lymphocyte ratio (NLR) and nutritional risk index (NRI) indicators before surgery to predict 90-day complications and mortality in a cohort of patients with complicated chronic pancreatitis and cancer of the head of the pancreas. METHODS: We evaluated preoperative levels of NLR and NRI among 225 subjects treated at different centres located in three countries. Short-term outcomes included length of hospital stay, postoperative complications, and mortality at 90 days and were appreciated based on NLR and NRI. The level of physiological stress was divided according by the formulas: neutrophil-lymphocyte ratio (NLR) = (neutrophil count, %)/(lymphocyte count, %). The nutritional state of the patients was divided according to the INR: NRI = (1.519 × serum albumin, g/L) + (41.7 × present weight, kg / usual weight, kg)]. RESULTS: All patients were operated. An analysis of the operations performed in three institutions demonstrated mortality in chronic pancreatitis and pancreatic pseudocysts in 1.4%, in chronic pancreatitis and the presence of an inflammatory mass mainly in the pancreatic head in 1.2%, and in cancer of the pancreatic head in 5.9%. The mean preoperative NLR was normal in 33.8% of the patients, the mild physiologic stress level was 54.7%, and the moderate was 11.5% before surgery. 10.2% of patients had a normal nutritional status, 20% had mild, 19.6% had moderate, and 50.2% had severe malnutrition. In a univariate analysis, at the cutoff of NLR ≥ 9.5 (AUC = 0.803) and the cutoff of NRI ≤ 98.5 (AUC = 0.801), increasing the risk of complications was observed (hazard ratio, 2.01; 95% CI, 1.247-3.250, p = 0.006), but at the cutoff of NRI ≤ 83.55 (AUC = 0.81), we observed a survival difference in operated patients (hazard ratio, 2.15; 95% CI, 1.334-3.477, p = 0.0025). CONCLUSIONS: Our study demonstrated that NLR and NRI were predictors of postoperative complications, but only NRI was a predictor of 90-day mortality in patients after surgery.

Investigate the Possibility of Using Phosphorescence in Clinical Oncology as an Early Prognostic Test in Detecting Brain Carcinogenesis.

Phosphorescence is considered one of the non-invasive glioblastoma testing methods based on studying molecular energy and the metabolism of L-tryptophan (Trp) through KP, which provides essential information on regulating immunity and neuronal function. This study aimed to conduct a feasibility study using phosphorescence in clinical oncology as an early prognostic test in detecting Glioblastoma. This study was conducted on 1039 patients who were operated on with follow-up between January 1, 2014, and December 1, 2022, and retrospectively evaluated in participating institutions in Ukraine (the Department of Oncology, Radiation Therapy, Oncosurgery, and Palliative Care at the Kharkiv National Medical University). Method of protein phosphorescence detection included two steps. During the first step, of luminol-dependent phosphorescence intensity in serum was carried out after its activation by the light source, according to the spectrofluorimeter method, as follows. At a temperature of 30 °C, serum drops were dried for 20 min to form a solid film. After that, we put the quartz plate with dried serum in a phosphoroscope of luminescent complex and measured the intensity. With the help of Max-Flux Diffraction Optic Parallel Beam Graded Multilayer Monochromator (Rigaku Americas Corporation) following spectral lines as 297, 313, 334, 365, 404, and 434 nm were distinguished and absorbed by serum film in the form of light quantum. The monochromator exit split width was 0.5 mm. Considering the limitations of each of the non-invasive tools currently available, phosphorescence-based diagnostic methods are ideally integrated into the NIGT platform: a non-invasive approach for visualizing a tumor and its main tumor characteristics in the spatial and temporal order. Because trp is present in virtually every cell in the body, these fluorescent and phosphorescent fingerprints can be used to detect cancer in many different organs. Using phosphorescence, it is possible to create predictive models for GBM in both primary and secondary diagnostics. This will assist clinicians in selecting the appropriate treatment option, monitoring treatment, and adapting to the era of patient-centered precision medicine.

Pancreatic Necrosis Infection as a Determinant of Multiple Organ Failure and Mortality in Acute Pancreatitis.

Several recommendations and data on the treatment of acute necrotizing pancreatitis (ANP) are conflicting and different surgical approaches continue to exist. We conducted a study on 148 patients with ANP, who were divided into two groups: the main group (n = 95) when the tactics of the step-up approach were applied with the principles of the concept of Enhanced Recovery After Surgery (ERAS) in order to determine this approach on effectiveness in reducing complications and 30-day mortality (2017-2022); the comparison group (n = 53) when the same tactic of the treatment was used without ERAS principles (2015-2016). Treatment time for the main group in the intensive care unit was minimized (p ≤ 0.004); it has been shown to reduce the frequency of complications in these patients (p < 0.001) requiring conservative or surgical treatment without general anaesthesia (Clavien-Dindo I-IIIa); no statistically significant differences were observed for the total incidence of Clavien-Dindo IIIb-IVb complications (p > 0.05); the median duration of treatment for patients in the primary group was 23 days, and in the reference group-34 days (p ≤ 0.003). Pancreatic infections have been observed in 92 (62.2%) patients and gram-negative bacteria predominated in the overall pathogen structure with 222 (70.7%) strains. The only evidence of multiple organ failure before (AUC = 0.814) and after surgery (AUC = 0.931) was found to be predictive of mortality. Antibiotic sensitivity of all isolated bacteria better understood local epidemiology and identified the most effective antibiotics when treating patients.

Mosaic translation hypothesis: chimeric polypeptides produced via multiple ribosomal frameshifting as a basis for adaptability.

How many different proteins can be produced from a single spliced transcript? Genome annotation projects overlook the coding potential of reading frames other than that of the reference open reading frames (refORFs). Recently, alternative open reading frames (altORFs) and their translational products, alternative proteins, have been shown to carry out important functions in various organisms. AltORFs overlapping refORFs or other altORFs in a different reading frame may be involved in one fundamental mechanism so far overlooked. A few years ago, it was proposed that altORFs may act as building blocks for chimeric (mosaic) polypeptides, which are produced via multiple ribosomal frameshifting events from a single mature transcript. We adopt terminology from that earlier discussion and call this mechanism mosaic translation. This way of extracting and combining genetic information may significantly increase proteome diversity. Thus, we hypothesize that this mechanism may have contributed to the flexibility and adaptability of organisms to a variety of environmental conditions. Specialized ribosomes acting as sensors probably played a central role in this process. Importantly, mosaic translation may be the main source of protein diversity in genomes that lack alternative splicing. The idea of mosaic translation is a testable hypothesis, although its direct demonstration is challenging. Should mosaic translation occur, we would currently highly underestimate the complexity of translation mechanisms and thus the proteome.

ASSOCIATION OF SCREENING MARKERS OF COAGULATION WITH THE SHORT-TERM OUTCOME IN THE SMALL BOWEL OBSTRUCTION IN ADULTS: A RETROSPECTIVE STUDY.

OBJECTIVE: The aim: To evaluate the possibility of using screening markers of coagulation to the assessment of severity and predict short-term outcomes in patients with small bowel obstruction. PATIENTS AND METHODS: Materials and methods: The study was based on the results of treatment of 71 patients 18-60 years old in 2019-2021. Patients were divided into two groups: in the 1st included those with a positive outcome (90.1%), and in the 2nd those with adverse outcomes (9.9%). RESULTS: Results: Only the laparoscopy approach has been in 12.5%, the laparotomy in 78.9%, and the hybrid in 9.9% of patients. There were no significant differences in screening tests of coagulation function indicators, including D-dimer, fibrinogen, Activated Partial Thromboplastin, International Normalised Ratio levels, and the International Society on Thrombosis and Hemostasis Criteria (ISTHC) score in two groups of patients before surgery. The predictive value of preoperative Sequential Organ Failure Assessment (SOFA) data (AUC = 0.844), serum lactate (AUC = 0.805), and systolic blood pressure (SPB) data (AUC = 0.808) before surgery were significant. The SOFA (AUC = 0.844) and APACHE II scores (AUC = 0.802), serum lactate (AUC = 0.884), D-dimer (AUC = 0.812), Antithrombin (AUC = 0.815), and CRP (AUC = 0.856) levels, SPB (0.856) within the first 72 hours after surgery were also good predictors of short-term outcomes (P = 0.000). CONCLUSION: Conclusions: It was confirmed that three parameters were predictors of early mortality before surgery, none of them included parameters of coagulation and seven parameters via 72 hours after surgery, which had included some parameters of coagulation.

Postoperative pain management in non-traumatic emergency general surgery: WSES-GAIS-SIAARTI-AAST guidelines.

BACKGROUND: Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team. MATERIAL AND METHODS: An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript. CONCLUSION: Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies.

SURGICAL TREATMENT OF ACUTE SMALL BOWEL OBSTRUCTION: CLINICAL AND LABORATORY PARAMETERS ASSOCIATED WITH STRANGULATION AND EARLY MORTALITY AFTER SURGERY.

OBJECTIVE: The aim: The study aimed to evaluate some criteria for preoperative diagnosis of strangulation and significant indicators of the prognosis of short-term outcomes in patients with small bowel obstruction. PATIENTS AND METHODS: Materials and methods: The results of the treatment of 123 patients aged 18-70 years with SBO were evaluated. RESULTS: Results: All of these patients underwent emergency surgery, and 22 patients (17.9%) have died. It has been shown that four lab parameters (blood leukocytes, lactate, intestinal fatty acid-binding protein, and C-reactive protein levels) and one instrumental (involving the mesentery of the small intestine, free fluid in the abdomen during CT) with 80% probability or more were associated with the strangulation type of SBO (Λ=0.276, p = 0.000). Three lab indicators (WBC count, serum lactate, and intestinal fatty acid-binding protein levels) and two clinical parameters (abdominal perfusion pressure level and the presence of abdominal sepsis) were associated with early mortality after surgery (Λ=0.626, p = 0.000) with the same probability. Immediate results of the treatment in these patients depended on the development of intra-abdominal complications after surgery (P = 0.024) and the need for early reoperation (P = 0.006) as well as the development of cardiovascular dysfunction (P = 0.000) and respiratory dysfunction (P = 0.000). CONCLUSION: Conclusions: There were confirmed parameters that were significantly associated with strangulation before surgery and short-term in-hospital mortality with an 80% probability or more. This made it possible to develop new mathematical models for the diagnosis of strangulated bowel obstruction and early postoperative mortality with an accuracy of 84.5% and 84.2%, respectively.

GmVTL1a is an iron transporter on the symbiosome membrane of soybean with an important role in nitrogen fixation.

Legumes establish symbiotic relationships with soil bacteria (rhizobia), housed in nodules on roots. The plant supplies carbon substrates and other nutrients to the bacteria in exchange for fixed nitrogen. The exchange occurs across a plant-derived symbiosome membrane (SM), which encloses rhizobia to form a symbiosome. Iron supplied by the plant is crucial for rhizobial enzyme nitrogenase that catalyses nitrogen fixation, but the SM iron transporter has not been identified. We use yeast complementation, real-time PCR and proteomics to study putative soybean (Glycine max) iron transporters GmVTL1a and GmVTL1b and have characterized the role of GmVTL1a using complementation in plant mutants, hairy root transformation and microscopy. GmVTL1a and GmVTL1b are members of the vacuolar iron transporter family and homologous to Lotus japonicus SEN1 (LjSEN1), which is essential for nitrogen fixation. GmVTL1a expression is enhanced in nodule infected cells and both proteins are localized to the SM. GmVTL1a transports iron in yeast and restores nitrogen fixation when expressed in the Ljsen1 mutant. Three GmVTL1a amino acid substitutions that block nitrogen fixation in Ljsen1 plants reduce iron transport in yeast. We conclude GmVTL1a is responsible for transport of iron across the SM to bacteroids and plays a crucial role in the nitrogen-fixing symbiosis.

An Iron-Activated Citrate Transporter, MtMATE67, Is Required for Symbiotic Nitrogen Fixation.

Iron (Fe) is an essential micronutrient for symbiotic nitrogen fixation in legume nodules, where it is required for the activity of bacterial nitrogenase, plant leghemoglobin, respiratory oxidases, and other Fe proteins in both organisms. Fe solubility and transport within and between plant tissues is facilitated by organic chelators, such as nicotianamine and citrate. We have characterized a nodule-specific citrate transporter of the multidrug and toxic compound extrusion family, MtMATE67 of Medicago truncatula The MtMATE67 gene was induced early during nodule development and expressed primarily in the invasion zone of mature nodules. The MtMATE67 protein was localized to the plasma membrane of nodule cells and also the symbiosome membrane surrounding bacteroids in infected cells. In oocytes, MtMATE67 transported citrate out of cells in an Fe-activated manner. Loss of MtMATE67 gene function resulted in accumulation of Fe in the apoplasm of nodule cells and a substantial decrease in symbiotic nitrogen fixation and plant growth. Taken together, the results point to a primary role of MtMATE67 in citrate efflux from nodule cells in response to an Fe signal. This efflux is necessary to ensure Fe(III) solubility and mobility in the apoplasm and uptake into nodule cells. Likewise, MtMATE67-mediated citrate transport into the symbiosome space would increase the solubility and availability of Fe(III) for rhizobial bacteroids.

Medicago truncatula natural resistance-associated macrophage Protein1 is required for iron uptake by rhizobia-infected nodule cells.

Iron is critical for symbiotic nitrogen fixation (SNF) as a key component of multiple ferroproteins involved in this biological process. In the model legume Medicago truncatula, iron is delivered by the vasculature to the infection/maturation zone (zone II) of the nodule, where it is released to the apoplast. From there, plasma membrane iron transporters move it into rhizobia-containing cells, where iron is used as the cofactor of multiple plant and rhizobial proteins (e.g. plant leghemoglobin and bacterial nitrogenase). MtNramp1 (Medtr3g088460) is the M. truncatula Natural Resistance-Associated Macrophage Protein family member, with the highest expression levels in roots and nodules. Immunolocalization studies indicate that MtNramp1 is mainly targeted to the plasma membrane. A loss-of-function nramp1 mutant exhibited reduced growth compared with the wild type under symbiotic conditions, but not when fertilized with mineral nitrogen. Nitrogenase activity was low in the mutant, whereas exogenous iron and expression of wild-type MtNramp1 in mutant nodules increased nitrogen fixation to normal levels. These data are consistent with a model in which MtNramp1 is the main transporter responsible for apoplastic iron uptake by rhizobia-infected cells in zone II.