Laparoscopic right colectomy: correct technique based on key anatomical principles.

Since the early1990s, laparoscopic right colon resections have been the most performed advanced laparoscopic procedures just after laparoscopic left colectomies and sigmoid resections. Indications for laparoscopic right colectomies are either benign or malignant diseases. Despite its many indications, a laparoscopic right or extended right colectomy is mostly performed for cancer of the caecum, the ascending colon, the hepatic flexure or the proximal transverse colon. Worldwide, colorectal cancer is the third most diagnosed cancer: an estimated 1,880,725 people were diagnosed with colorectal cancer in 2020, out of which 1,148,515 were colon cancer cases and 40% were located in the right colon. These figures make an oncologic sound surgery for right colon cancer of the utmost relevance. More recently, complete mesocolic excision has been advocated as the optimal choice in term of radicality, especially in node-positive patients with right colon cancer. Laparoscopic standard right colectomy and extended right colectomy with or without CME should be performed according to defined principles based on a close knowledge of key anatomical landmarks. This knowledge will allow to trace anatomical structures and drive instruments along the correct surgical planes and has its foundations in teachings from surgeons and scientists of past and present time.

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS).

OBJECTIVE: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. SUMMARY BACKGROUND DATA: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. METHODS: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. RESULTS: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. CONCLUSIONS: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.

Pulmonary Circulation Under Pressure: Pathophysiological and Therapeutic Implications of BK Channel.

The large-conductance Ca2+-activated K+ (BK) channel is widely expressed in the pulmonary blood vessels and plays a significant role in regulating pulmonary vascular tonus. It opens under membrane depolarization, increased intracellular Ca+2 concentration, and chronic hypoxia, resulting in massive K+ efflux, membrane hyperpolarization, decreased L-type Ca+2 channel opening, and smooth muscle relaxation. Several reports have demonstrated an association between BK channel dysfunction and pulmonary hypertension (PH) development. Decreased BK channel subunit expression and impaired regulation by paracrine hormones result in decreased BK channel opening, increased pulmonary vascular resistance, and pulmonary arterial pressure being the cornerstone of PH. The resulting right ventricular pressure overload ultimately leads to ventricular remodeling and failure. Therefore, it is unsurprising that the BK channel has arisen as a potential target for treating PH. Recently, a series of selective, synthetic BK channel agonists have proven effective in attenuating the pathophysiological progression of PH without adverse effects in animal models.

A venetoclax and azacitidine bridge-to-transplant strategy for NPM1-mutated acute myeloid leukaemia in molecular failure.

NPM1-mutated acute myeloid leukaemia (NPM1mut AML) represents a mostly favourable/intermediate risk disease that benefits from allogeneic haematopoietic stem cell transplantation (HSCT) in case of measurable residual disease (MRD) relapse or persistence after induction chemotherapy. Although the negative prognostic role of pre-HSCT MRD is established, no recommendations are available for the management of peri-transplant molecular failure (MF). Based on the efficacy data of venetoclax (VEN)-based treatment in NPM1mut AML older patients, we retrospectively analysed the off-label combination of VEN plus azacitidine (AZA) as bridge-to-transplant strategy in 11 NPM1mut MRD-positive fit AML patients. Patients were in MRD-positive complete remission (CRMRDpos ) at the time of treatment: nine in molecular relapse and two in molecular persistence. After a median number of two cycles (range 1-4) of VEN-AZA, 9/11 (81.8%) achieved CRMRD -negative (CRMRDneg ). All 11 patients proceeded to HSCT. With a median follow-up from treatment start of 26 months, and a median post-HSCT follow-up of 19 months, 10/11 patients are alive (1 died from non-relapse mortality), and 9/10 patients are in MRDneg status. This patient series highlights the efficacy and safety of VEN-AZA to prevent overt relapse, achieve deep responses and preserve patient fitness before HSCT, in patients with NPM1mut AML in MF.

Towards Truly "Bespoke" Robotic Surgery: Vessel-Sparing Sigmoidectomy.

The proposed video-vignette represents a later step towards a truly robotically surgical approach, that combines oncological radicality and preservation of optimal blood flow during a sigmoidectomy for cancer. This totally robotic vessel-sparing approach doesn't result in longer operative times, higher blood loss or extended length of hospitalization.

Comparison between side-lying and standing positions for hip abductor strength assessment.

BACKGROUND: The hip abductor muscles control the pelvis in the frontal plane and allow the maintenance of trunk position and dynamic balance during weight-bearing activities. OBJECTIVE: To compare the side-lying and standing positions for hip abductor strength assessment with regards to torque production and myolectric activity. METHOD: Concentric and eccentric hip abductor peak torque and total work, and myoelectric activity of the tensor fascia lata, gluteus medius, and inferior and superior portions of the gluteus maximus muscles were measured during maximal isokinetic tests for hip abductor strength in the side-lying and standing positions. The Wilcoxon test was used to compare variables between the positions. RESULTS: Peak torque values did not differ between side-lying and standing positions for both concentric and eccentric contraction modes (p > .05). During standing position, greater concentric total work was observed (p = .013). This position resulted in a lower activity of the tensor fascia lata muscle (p = .005) compared to side lying position. Myoelectric activity of gluteus medius, and inferior and superior portions of the gluteus maximus was similar between positions (p > .05). CONCLUSION: Both positions presented similar peak torque values and, during the standing position, a greater concentric total work and lesser activation of the tensor fascia lata was observed. Standing position can be used when emphasis on the superior portion of gluteus maximus over the tensor fascia lata is intended.

Salmonella Typhimurium O-antigen and VisP play an important role in swarming and osmotic stress response during intracellular conditions.

Salmonella Typhimurium is a pathogen of clinical relevance and a model of study in host-pathogen interactions. The virulence and stress-related periplasmic protein VisP is important during S. Typhimurium pathogenesis. It supports bacteria invading host cells, surviving inside macrophages, swimming, and succeeding in murine colitis model, O-antigen assembly, and responding to cationic antimicrobial peptides. This study aimed to investigate the role of the O-antigen molecular ruler WzzST and the periplasmic protein VisP in swarming motility and osmotic stress response. Lambda red mutagenesis was performed to generate single and double mutants, followed by swarming motility, qRT-PCR, Western blot, and growth curves. Here we demonstrate that the deletion of visP affects swarming under osmotic stress and changes the expression levels of genes responsible for chemotaxis, flagella assembly, and general stress response. The deletion of the gene encoding for the O-antigen co-polymerase wzzST increases swarming motility but not under osmotic stress. A second mutation in O-antigen co-polymerase wzzST in a ΔvisP background affected gene expression levels. The ΔvisP growth was affected by sodium and magnesium levels on N-minimum media. These data indicate that WzzST has a role in swarming the motility of S. Typhimurium, as the VisP is involved in chemotaxis and osmotic stress, specifically in response to MgCl2 and NaCl.

Preservation of the inferior mesenteric artery in laparoscopic nerve-sparing colorectal surgery for endometriosis.

Laparoscopic rectosigmoid resection for endometriosis is usually performed with the section of the inferior mesenteric artery (IMA) distal to the left colic artery (low-tie ligation). This study was to determine outcomes in IMA-sparing surgery in endometriosis cases. A single-center retrospective study based on the analysis of clinical notes of women who underwent laparoscopic rectosigmoid segmental resection and IMA-sparing surgery for deep infiltrating endometriosis with bowel involvement between March the 1st, 2018 and February the 29th, 2020 in a referral hospital. During the study period, 1497 patients had major gynecological surgery in our referral center, of whom 253 (17%) for endometriosis. Of the 100 patients (39%) who had bowel endometriosis, 56 underwent laparoscopic nerve-sparing rectosigmoid segmental resection and IMA-sparing surgery was performed in 53 cases (95%). Short-term complications occurred in 4 cases (7%) without any case of anastomotic leak. Preservation of the IMA in colorectal surgery for endometriosis is feasible, safe and enables a tension-free anastomosis without an increase of postoperative complication rates.

Piper tectoniifolium Kunth: A New Natural Source of the Bioactive Neolignan (-)-Grandisin.

The Piper species are a recognized botanical source of a broad structural diversity of lignans and its derivatives. For the first time, Piper tectoniifolium Kunth is presented as a promising natural source of the bioactive (-)-grandisin. Phytochemical analyses of extracts from its leaves, branches and inflorescences showed the presence of the target compound in large amounts, with leaf extracts found to contain up to 52.78% in its composition. A new HPLC-DAD-UV method was developed and validated to be selective for the identification of (-)-grandisin being sensitive, linear, precise, exact, robust and with a recovery above 90%. The absolute configuration of the molecule was determined by X-ray diffraction. Despite the identification of several enantiomers in plant extracts, the major isolated substance was characterized to be the (-)-grandisin enantiomer. In vascular reactivity tests, it was shown that the grandisin purified from botanical extracts presented an endothelium-dependent vasorelaxant effect with an IC50 of 9.8 ± 1.22 µM and around 80% relaxation at 30 µM. These results suggest that P. tectoniifolium has the potential to serve as a renewable source of grandisin on a large scale and the potential to serve as template for development of new drugs for vascular diseases with emphasis on disorders related to endothelial disfunction.

Genome profiling of fluoroquinolone-resistant uropathogenic Escherichia coli isolates from Brazil.

Urinary tract infections (UTIs) are a major public health concern in both community and hospital settings worldwide. Uropathogenic Escherichia coli (UPEC) is the main causative agent of UTI and increasingly associated with antibiotic resistance. Herein, we report the draft genome sequence of 9 fluoroquinolone-resistant UPEC isolates from Brazil and examine selected major phenotypic features, such as antimicrobial resistance profile, phylogroup, serotype, sequence type (ST), virulence genes, and resistance marks. Besides the quinolone resistance, beta-lactams, ESBL production, aminoglycosides, and tetracycline resistance were observed. High prevalence of 20 virulence genes was detected in all isolates, such as those encoding type 1 fimbriae, acid tolerance system, and hemolysin E, particularly within E. coli B2 phylogroup, as ST131 and ST1193 strains, among other genomic analyses as genomic islands, resistance plasmids, and integron identification.

Coronary arterial geometry: A comprehensive comparison of two imaging modalities.

The characterization of vascular geometry is a fundamental step towards the correct interpretation of coronary artery disease. In this work, we report a comprehensive comparison of the geometry featured by coronary vessels as obtained from coronary computed tomography angiography (CCTA) and the combination of intravascular ultrasound (IVUS) with bi-plane angiography (AX) modalities. We analyzed 34 vessels from 28 patients with coronary disease, which were deferred to CCTA and IVUS procedures. We discuss agreement and discrepancies between several geometric indexes extracted from vascular geometries. Such an analysis allows us to understand to which extent the coronary vascular geometry can be reliable in the interpretation of geometric risk factors, and as a surrogate to characterize coronary artery disease.

BKCa Channel Activation Attenuates the Pathophysiological Progression of Monocrotaline-Induced Pulmonary Arterial Hypertension in Wistar Rats.

PURPOSE: In the present study, the therapeutic efficacy of a selective BKCa channel opener (compound X) in the treatment of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) was investigated. METHODS: PAH was induced in male Wistar rats by a single injection of MCT. After two weeks, the MCT-treated group was divided into two groups that were either treated with compound X or vehicle. Compound X was administered daily at 28 mg/kg. Electrocardiographic, echocardiographic, and haemodynamic analyses were performed; ex vivo evaluations of pulmonary artery reactivity, right ventricle (RV) and lung histology as well as expression levels of α and ß myosin heavy chain, brain natriuretic peptide, and cytokines (TNFα and IL10) in heart tissue were performed. RESULTS: Pulmonary artery rings of the PAH group showed a lower vasodilatation response to acetylcholine, suggesting endothelial dysfunction. Compound X promoted strong vasodilation in pulmonary artery rings of both control and MCT-induced PAH rats. The untreated hypertensive rats presented remodelling of pulmonary arterioles associated with increased resistance to pulmonary flow; increased systolic pressure, hypertrophy and fibrosis of the RV; prolongation of the QT and Tpeak-Tend intervals (evaluated during electrocardiogram); increased lung and liver weights; and autonomic imbalance with predominance of sympathetic activity. On the other hand, treatment with compound X reduced pulmonary vascular remodelling, pulmonary flow resistance and RV hypertrophy and afterload. CONCLUSION: The use of a selective and potent opener to activate the BKCa channels promoted improvement of haemodynamic parameters and consequent prevention of RV maladaptive remodelling in rats with MCT-induced PAH.

Antibacterial activities and antiproliferative assays over a tumor cells panel of a silver complex with 4-aminobenzoic acid: Studies in vitro of sustained release using bacterial cellulose membranes as support.

The aims of this work were to evaluate the antibacterial and antiproliferative potential in vitro of the metal complex with 4-aminobenzoic acid (Ag-pABA) and a drug delivery system based on bacterial cellulose (BC-Ag-pABA). The Ag-pABA complex was characterized by elemental analysis, high resolution mass spectrometry and single-crystal X-ray diffraction techniques, which indicated a 1:2 metal/pABA composition plus a nitrate ion coordinated to silver by the oxygen atom, with the coordination formula [Ag (C7H7NO2)2(NO3)]. The coordination of pABA to the silver ion occurred by the nitrogen atom. The in vitro antibacterial activity of the complex evaluated by minimum inhibitory concentration assays demonstrated the effective growth inhibitory activity against Gram-positive, Gram-negative biofilm producers and acid-alcohol resistant Bacillus. The antiproliferative activities against a panel of eight tumor cells demonstrated the activity of the complex with a significant selectivity index (SI). The DNA interaction capacity and the Ames Test indicated the absence of mutagenicity. The BC-Ag-pABA composite showed an effective capacity of sustained release of Ag-pABA. The observed results validate further studies on its mechanisms of action and the conditions that mediate the in vivo biological effects using animal models to confirm its safety and effectiveness for treatment of skin and soft tissues infected by bacterial pathogens, urinary tract infections and cancer.

Anabolic steroid excess promotes hydroelectrolytic and autonomic imbalance in adult male rats: Is it enough to alter blood pressure?

AIM: The present study investigated the effects of anabolic steroid (AS) excess on blood pressure regulation. METHODS: Male Wistar rats were treated with nandrolone decanoate (AS) or vehicle (CTL) for 8 or 10 weeks. Saline (1.8%) and water intake were measured in metabolic cages. Urinary volume, osmolarity, Na+ and K+ concentrations, and plasma osmolarity were measured. The autonomic balance was estimated by heart rate variability at baseline or after icv injection of losartan. Cardiac function was assessed by echocardiography and ex vivo recordings. Myocardial collagen deposition was evaluated by Picrosirius-Red staining. Vascular reactivity and wall thickness were investigated in aortic sections. Blood pressure (BP) was assessed by tail-cuff plethysmography. Angiotensin II type I receptor (AT1R), renin, and mineralocorticoid receptor (MR) mRNA expression was measured in the kidneys and whole hypothalamus. RESULTS: AS group exhibited decreased urinary volume and Na+ concentration, while urinary K+ concentration, plasma osmolarity, and renal AT1R and renin mRNA levels were increased compared to CTL (p < 0.05). Water intake was increased, and saline intake was decreased in the AS group (p < 0.01). AS group exhibited increased low-frequency/high-frequency-ratio, while it was decreased by icv injection of losartan (p < 0.05) compared to baseline. Neither cardiac function nor vascular reactivity/morphology was affected by AS excess (p > 0.05). Ultimately, BP levels were not altered by AS excess (p > 0.05). CONCLUSION: AS excess promoted hydroelectrolytic and autonomic imbalance but did not alter vascular or cardiac function/morphology.

Chronic total occlusion percutaneous coronary intervention in Latin America.

OBJECTIVES: To report clinical, angiographic characteristics, outcomes, and predictors of unsuccessful procedures in patients who underwent chronic total occlusion (CTO) percutaneous coronary interventions (PCI) in Latin America. BACKGROUND: CTO PCI has been increasingly performed worldwide, but there is a lack of information in this region. METHODS: An international multicenter registry was developed to collect data on CTO PCI performed in centers in Latin America. Patient, angiographic, procedural and outcome data were evaluated. Predictors of unsuccessful procedures were assessed by multivariable analysis. RESULTS: We have included data related to 1,040 CTO PCIs performed in seven countries in Latin America (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, and Puerto Rico). The mean age was 64 ± 10 years, and CTO PCI was performed mainly for angina control (81%) or treatment of a large ischemic area (30%). Overall technical success rate was 82.5%, and it was achieved with antegrade wire escalation in 81%, antegrade dissection/re-entry in 8% and with retrograde techniques in 11% of the successful procedures. Multivariable analysis identified moderate/severe calcification, a blunt proximal cap and a previous attempt as independent predictors of unsuccessful procedures. In-hospital major adverse cardiovascular events (MACE) occurred in 3.1% of the cases, death in 1% and cardiac tamponade in 0.9% CONCLUSIONS: CTO PCI in Latin America has been performed mainly for ischemia relief. Procedures were associated with a success rate above 80% and low incidence of MACE. Predictors of unsuccessful procedures were similar to those previously reported in the literature.

Expression of potassium channels is relevant for cell survival and migration in a murine bone marrow stromal cell line.

S17 is a clonogenic bone marrow stromal (BMS) cell line derived from mouse that has been extensively used to assess both human and murine hematopoiesis support capacity. However, very little is known about the expression of potassium ion channels and their function in cell survival and migration in these cells. Thus, the present study was designed to characterize potassium ion channels using electrophysiological and molecular biological approaches in S17 BMS cells. The whole-cell configuration of the patch clamp technique has been applied to identify potassium ion currents and reverse transcription polymerase chain reaction (RT-PCR) used to determine their molecular identities. Based on gating kinetics and pharmacological modulation of the macroscopic currents we found the presence of four functional potassium ion channels in S17 BMS cells. These include a current rapidly activated and inactivated, tetraethylammonium-sensitive, (IKV ) in most (50%) cells; a fast activated and rapidly inactivating A-type K + current (IK A -like); a delayed rectifier K + current (IK DR ) and an inward rectifier potassium current (IK IR ), found in, respectively 4.5%, 26% and 24% of these cells. RT-PCR confirmed the presence of mRNA transcripts for the alpha subunit of the corresponding functional ion channels. Additionally, functional assays were performed to investigate the importance of potassium currents in cell survival and migration. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analyses revealed a reduction in cell viability, while wound healing assays revealed reduced migration potential in cells incubated with different potassium channel blockers. In conclusion, our data suggested that potassium currents might play a role in the maintenance of overall S17 cell ionic homeostasis directly affecting cell survival and migration.

Coronary fractional flow reserve derived from intravascular ultrasound imaging: Validation of a new computational method of fusion between anatomy and physiology.

OBJECTIVES: To evaluate the diagnostic performance of a novel computational algorithm based on three-dimensional intravascular ultrasound (IVUS) imaging in estimating fractional flow reserve (IVUSFR ), compared to gold-standard invasive measurements (FFRINVAS ). BACKGROUND: IVUS provides accurate anatomical evaluation of the lumen and vessel wall and has been validated as a useful tool to guide percutaneous coronary intervention. However, IVUS poorly represents the functional status (i.e., flow-related information) of the imaged vessel. METHODS: Patients with known or suspected stable coronary disease scheduled for elective cardiac catheterization underwent FFRINVAS measurement and IVUS imaging in the same procedure to evaluate intermediate lesions. A processing methodology was applied on IVUS to generate a computational mesh condensing the geometric characteristics of the vessel. Computation of IVUSFR was obtained from patient-level morphological definition of arterial districts and from territory-specific boundary conditions. FFRINVAS measurements were dichotomized at the 0.80 threshold to define hemodynamically significant lesions. RESULTS: A total of 24 patients with 34 vessels were analyzed. IVUSFR significantly correlated (r = 0.79; P < 0.001) and showed good agreement with FFRINVAS , with a mean difference of -0.008 ± 0.067 (P = 0.47). IVUSFR presented an overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 91%, 89%, 92%, 80%, and 96%, respectively, to detect significant stenosis. CONCLUSION: The computational processing of IVUSFR is a new method that allows the evaluation of the functional significance of coronary stenosis in an accurate way, enriching the anatomical information of grayscale IVUS.

Novel Role of VisP and the Wzz System during O-Antigen Assembly in Salmonella enterica Serovar Typhimurium Pathogenesis.

Salmonella enterica serovars are associated with diarrhea and gastroenteritis and are a helpful model for understanding host-pathogen mechanisms. Salmonella enterica serovar Typhimurium regulates the distribution of O antigen (OAg) and presents a trimodal distribution based on Wzy polymerase and the WzzST (long-chain-length OAg [L-OAg]) and WzzfepE (very-long-chain-length OAg [VL-OAg]) copolymerases; however, several mechanisms regulating this process remain unclear. Here, we report that LPS modifications modulate the infectious process and that OAg chain length determination plays an essential role during infection. An increase in VL-OAg is dependent on Wzy polymerase, which is promoted by a growth condition resembling the environment of Salmonella-containing vacuoles (SCVs). The virulence- and stress-related periplasmic protein (VisP) participates in OAg synthesis, as a ΔvisP mutant presents a semirough OAg phenotype. The ΔvisP mutant has greatly decreased motility and J774 macrophage survival in a colitis model of infection. Interestingly, the phenotype is restored after mutation of the wzzST or wzzfepE gene in a ΔvisP background. Loss of both the visP and wzzST genes promotes an imbalance in flagellin secretion. L-OAg may function as a shield against host immune systems in the beginning of an infectious process, and VL-OAg protects bacteria during SCV maturation and facilitates intramacrophage replication. Taken together, these data highlight the roles of OAg length in generating phenotypes during S Typhimurium pathogenesis and show the periplasmic protein VisP as a novel protein in the OAg biosynthesis pathway.