Oncological Outcomes and Response Rate After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Network Meta-Analysis Comparing Induction vs. Consolidation Chemotherapy vs. Standard Chemoradiation.

TNT is now considered the preferred option for stage II-III locally advanced rectal cancer (LARC). However, the prognostic benefit and optimal sequence of TNT remains unclear. This network meta-analysis (NMA) compared short- and long-term outcomes amongst patients with LARC receiving total neoadjuvant therapy (TNT) as induction (iTNT) or consolidation chemotherapy (cTNT) with those receiving neoadjuvant chemoradiation (nCRT) alone. A systematic literature search was performed between 2012 and 2023. A Bayesian NMA was conducted using a Markov Chain Monte Carlo method with a random-effects model and vague prior distribution to calculate odds ratios (OR) with 95% credible intervals (CrI). The surface under the cumulative ranking (SUCRA) curves were used to rank treatment(s) for each outcome. In total, 11 cohorts involving 8360 patients with LARC were included. There was no significant difference in disease-free survival (DFS) and overall survival (OS) amongst the 3 treatments. Compared with nCRT, both cTNT (OR 2.36; 95% CrI, 1.57-3.66) and iTNT (OR 1.99; 95% CrI, 1.44-2.95) significantly improved complete response (CR) rate. Notably, cTNT ranked as the best treatment for CR (SUCRA 0.90) and iTNT as the best treatment for 3-year DFS and OS (SUCRA 0.72 and 0.87, respectively). Both iTNT and cTNT strategies significantly improved CR rates compared with nCRT. cTNT was ranked highest for CR rates, while iTNT was ranked highest for 3-year survival outcomes. However, no other significant differences in DFS, OS, sphincter-saving surgery, R0 resection and postoperative complications were found amongst the treatment groups.

Brilacidin, a novel antifungal agent against Cryptococcus neoformans.

Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis. IMPORTANCE: Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.

A narrative on diversity, equity, and inclusion in surgery: insights from the European Society of Coloproctology and identification of points for action.

The focus of the 2022 European Society of Coloproctology (ESCP) annual campaign was diversity, equity, and inclusion (DEI) in surgery. The ESCP "Operation Equal Access" campaign sought to interview key-opinion leaders and trainees, to raise awareness on inequalities, inform the community of the status of the topic, and to identify future areas for improvement. The ESCP Social Media Working Group interviewed experts who have made significant contributions to DEI in colorectal surgery and were acknowledged opinion leaders in the field. The interviews focused on their career, professional life, experiences, and opportunities during their training, and their views on DEI in colorectal surgery. DEI principles, education, and values need further promotion to reduce and address bias within the profession and overall improve the experience of minority community including health professionals and patients. International Societies are working to facilitate training opportunities and overcome DEI, and networking have contributed to that. Collaborations between societies will be pivotal to contribute to offering research and leadership opportunities equally. Access to advanced workshops including cadaveric training and simulation can be consistently promoted and provided globally via societies through telemonitoring. Involving patients in research should be encouraged, as it brings the perspective of a living experience.

Membrane Phenotypic, Metabolic and Genotypic Adaptations of Streptococcus oralis Strains Destined to Rapidly Develop Stable, High-Level Daptomycin Resistance during Daptomycin Exposures.

The Streptococcus mitis-oralis subgroup of viridans group streptococci are important human pathogens. We previously showed that a substantial portion of S. mitis-oralis strains (>25%) are 'destined' to develop rapid, high-level, and stable daptomycin (DAP) resistance (DAP-R) during DAP exposures in vitro. Such DAP-R is often accompanied by perturbations in distinct membrane phenotypes and metabolic pathways. The current study evaluated two S. oralis bloodstream isolates, 73 and 205. Strain 73 developed stable, high-level DAP-R (minimum inhibitory concentration [MIC] > 256 µg/mL) within 2 days of in vitro DAP passage ("high level" DAP-R [HLDR]). In contrast, strain 205 evolved low-level and unstable DAP-R (MIC = 8 µg/mL) under the same exposure conditions in vitro ("non-HLDR"). Comparing the parental 73 vs. 73-D2 (HLDR) strain-pair, we observed the 73-D2 had the following major differences: (i) altered cell membrane (CM) phospholipid profiles, featuring the disappearance of phosphatidylglycerol (PG) and cardiolipin (CL), with accumulation of the PG-CL pathway precursor, phosphatidic acid (PA); (ii) enhanced CM fluidity; (iii) increased DAP surface binding; (iv) reduced growth rates; (v) decreased glucose utilization and lactate accumulation; and (vi) increased enzymatic activity within the glycolytic (i.e., lactate dehydrogenase [LDH]) and lipid biosynthetic (glycerol-3-phosphate dehydrogenase [GPDH]) pathways. In contrast, the 205 (non-HLDR) strain-pair did not show these same phenotypic or metabolic changes over the 2-day DAP exposure. WGS analyses confirmed the presence of mutations in genes involved in the above glycolytic and phospholipid biosynthetic pathways in the 73-D2 passage variant. These data suggest that S. oralis strains which are 'destined' to rapidly develop HLDR do so via a conserved cadre of genotypic, membrane phenotypic, and metabolic adaptations.

Combinations of Daptomycin plus Ceftriaxone, but Not Ascending Daptomycin Dose-Regimens, Are Effective in Experimental Endocarditis Caused by Streptococcus mitis-oralis Strains: Target Tissue Clearances and Prevention of Emergence of Daptomycin-Resistance.

The Streptococcus mitis-oralis subgroup of the viridans group streptococci (VGS) are the most common cause of infective endocarditis (IE) in many parts of the world. These organisms are frequently resistant in vitro to standard ß-lactams (e.g., penicillin; ceftriaxone [CRO]), and have the notable capacity for rapidly developing high-level and durable daptomycin resistance (DAP-R) during exposures in vitro, ex vivo, and in vivo. In this study, we used 2 prototypic DAP-susceptible (DAP-S) S. mitis-oralis strains (351; and SF100), which both evolved stable, high-level DAP-R in vitro within 1 to 3 days of DAP passage (5 to 20 µg/mL DAP). Of note, the combination of DAP + CRO prevented this rapid emergence of DAP-R in both strains during in vitro passage. The experimental rabbit IE model was then employed to quantify both the clearance of these strains from multiple target tissues, as well as the emergence of DAP-R in vivo under the following treatment conditions: (i) ascending DAP-alone dose-strategies encompassing human standard-dose and high-dose-regimens; and (ii) combinations of DAP + CRO on these same metrics. Ascending DAP-alone dose-regimens (4 to 18 mg/kg/d) were relatively ineffective at either reducing target organ bioburdens or preventing emergence of DAP-R in vivo. In contrast, the combination of DAP (4 or 8 mg/kg/d) + CRO was effective at clearing both strains from multiple target tissues (often with sterilization of bio-burdens in such organs), as well as preventing the emergence of DAP-R. In patients with serious S. mitis-oralis infections such as IE, especially caused by strains exhibiting intrinsic ß-lactam resistance, initial therapy with combinations of DAP + CRO may be warranted.

Impact of Bicarbonate on PBP2a Production, Maturation, and Functionality in Methicillin-Resistant Staphylococcus aureus (MRSA).

Certain methicillin-resistant Staphylococcus aureus (MRSA) strains exhibit ß-lactam-susceptibility in vitro, ex vivo and in vivo in the presence of NaHCO3 (NaHCO3-responsive MRSA). Herein, we investigate the impact of NaHCO3 on factors required for PBP2a functionality. Prototype NaHCO3-responsive and -nonresponsive MRSA strains (as defined in vitro) were assessed for the impact of NaHCO3 on: expression of genes involved in PBP2a production-maturation pathways (mecA, blaZ, pbp4, vraSR, prsA, sigB, and floA); membrane PBP2a and PrsA protein content; and membrane carotenoid content. Following NaHCO3 exposure in NaHCO3-responsive (vs - nonresponsive) MRSA, there was significantly reduced expression of: i) mecA and blaZ; ii) the vraSR-prsA gene axis; and iii) pbp4 Carotenoid production was reduced, while floA expression was increased by NaHCO3 exposure in all MRSA strains. This work underscores the distinct regulatory impact of NaHCO3 on a cadre of genes encoding factors required for maintenance of the MRSA phenotype through PBP2a functionality and maturation.

A prospective study of diagnostic accuracy of multidisciplinary team and radiology reporting of preoperative colorectal cancer local staging.

INTRODUCTION: The aim of this study was to correlate and assess diagnostic accuracy of preoperative staging at multidisciplinary team meeting (MDT) against the original radiology reports and pathological staging in colorectal cancer patients. METHODS: A prospective observational study was conducted at two institutions. Patients with histologically proven colorectal cancer and available preoperative imaging were included. Preoperative tumor and nodal staging (cT and cN) as determined by the MDT and the radiology report (computed tomography [CT] and/or magnetic resonance imaging [MRI]) were recorded. Kappa statistics were used to assess agreement between MDT and the radiology report for cN staging in colon cancer, cT and cN in rectal cancer, and tumor regression grade (TRG) in patients with rectal cancer who received neoadjuvant therapy. Pathological report after surgery served as the reference standard for local staging, and AUROC curves were constructed to compare diagnostic accuracy of the MDT and radiology report. RESULTS: A total of 481 patients were included. Agreement between MDT and radiology report for cN stage was good in colon cancer (k = .756, Confidence Interval (CI) 95% .686-.826). Agreement for cT and cN and in rectal cancer was very good (kw = .825, CI 95% .758-.892) and good (kw = .792, CI 95% .709-.875), respectively. In the rectal cancer group that received neoadjuvant therapy, agreement on TRG was very good (kw = .919, CI 95% .846-.993). AUROC curves using pathological staging indicated no difference in diagnostic accuracy between MDT and radiology reports for either colon or rectal cancer. CONCLUSION: Preoperative colorectal cancer local staging was consistent between specialist MDT review and original radiology reports, with no significant differences in diagnostic accuracy identified.

Outcomes of open vs laparoscopic vs robotic vs transanal total mesorectal excision (TME) for rectal cancer: a network meta-analysis.

BACKGROUND: Total mesorectal excision (TME) for rectal cancer can be achieved using open (OpTME), laparoscopic (LapTME), robotic (RoTME), or transanal techniques (TaTME). However, the optimal approach for access remains controversial. The aim of this network meta-analysis was to assess operative and oncological outcomes of all four surgical techniques. METHODS: Ovid MEDLINE, EMBASE, and PubMed databases were searched systematically from inception to September 2020, for randomised controlled trials (RCTs) comparing any two TME surgical techniques. A network meta-analysis using a Bayesian random-effects framework and mixed treatment comparison was performed. Primary outcomes were the rate of clear circumferential resection margin (CRM), defined as > 1 mm from the closest tumour to the cut edge of the tissue, and completeness of mesorectal excision. Secondary outcomes included radial and distal resection margin distance, postoperative complications, locoregional recurrence, disease-free survival, and overall survival. Surface under cumulative ranking (SUCRA) was used to rank the relative effectiveness of each intervention for each outcome. The higher the SUCRA value, the higher the likelihood that the intervention is in the top rank or one of the top ranks. RESULTS: Thirty-two RCTs with a total of 6151 patients were included. Compared with OpTME, there was no difference in the rates of clear CRM: LapTME RR = 0.99 (95% (Credible interval) CrI 0.97-1.0); RoTME RR = 1.0 (95% CrI 0.96-1.1); TaTME RR = 1.0 (95% CrI 0.96-1.1). There was no difference in the rates of complete mesorectal excision: LapTME RR = 0.98 (95% CrI 0.98-1.1); RoTME RR = 1.1 (95% CrI 0.98-1.4); TaTME RR = 1.0 (95% CrI 0.91-1.2). RoTME was associated with improved distal resection margin distance compared to other techniques (SUCRA 99%). LapTME had a higher rate of conversion to open surgery when compared with RoTME: RoTME RR = 0.23 (95% CrI 0.034-0.70). Length of stay was shortest in RoTME compared to other surgical approaches: OpTME mean difference in days (MD) 3.3 (95% CrI 0.12-6.0); LapTME MD 1.7 (95% CrI - 1.1-4.4); TaTME MD 1.3 (95% CrI - 5.2-7.4). There were no differences in 5-year overall survival (LapTME HR 1.1, 95% CrI 0.74, 1.4; TaTME HR 1.7, 95% CrI 0.79, 3.4), disease-free survival rates (LapTME HR 1.1, 95% CrI 0.76, 1.4; TaTME HR 1.1, 95% CrI 0.52, 2.4), or anastomotic leakage (LapTME RR = 0.92 (95% CrI 0.63, 1.1); RoTME RR = 1.0 (95% CrI 0.48, 1.8); TaTME RR = 0.53 (95% CrI 0.19, 1.2). The overall quality of evidence as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessments across all outcomes including primary and secondary outcomes was deemed low. CONCLUSIONS: In selected patients eligible for a RCT, RoTME achieved improved distal resection margin distance and a shorter length of hospital stay. No other differences were observed in oncological or recovery parameters between (OpTME), laparoscopic (LapTME), robotic (RoTME), or trans-anal TME (TaTME). However, the overall quality of evidence across all outcomes was deemed low.

Pre-treatment delay and out of pocket expenses by notified new tuberculosis patients in an Indian mega city.

BACKGROUND: Study was carried out to find out delay from onset of symptoms and out of pocket expenditure (OOPE) until initiation of anti-TB treatment (ATT) by new Tuberculosis (TB) patients registered in public health facilities in Bengaluru. METHODS: Notified patients (N = 228) selected purposively were interviewed at initiation of ATT regarding number and type of facilities visited and delay in initiating ATT. OOPE was elicited separately for in- and out-patient visits, towards consultation, purchase of medicines, diagnostic tests, transportation, hospitalization and food. Dissaving or money borrowed was ascertained. RESULTS: Two-thirds of participants were 15-44 years of age and 56% were males, mean annual household income was $4357. About 75% first visited a private health facility; 68% and 87% respectively were diagnosed and started on ATT in public sector after visiting an average of three facilities and after a mean delay of 68 days; the median delay was 44 days. Of mean OOPE of $402, 54% was direct medical expenditure, 5% non-medical direct and 41% indirect. OOPE was higher for Extra-pulmonary TB compared to PTB and when number of health facilities visited before initiating treatment was >3 compared to those who visited ≤3 and when the time interval between onset of symptoms and treatment initiation (total delay) was >28 days compared to when this interval was ≤28 days. About 20% suffered catastrophic expenditure; 34% borrowed money and 37% sold assets. CONCLUSION: Concerted efforts are needed to reduce delay and OOPE in pre-treatment period and social protection to account for indirect expenditure.

Activity of the Lactate Dehydrogenase Inhibitor Oxamic Acid against the Fermentative Bacterium Streptococcus mitis/oralis: Bactericidal Effects and Prevention of Daptomycin Resistance In Vitro and in an Ex Vivo Model.

Streptococcus mitis/oralis is a fermentative bacterium that relies on lactate dehydrogenase to balance its redox poise and keep glycolysis active. Metabolomic analysis of an in vitro-derived daptomycin-resistant (DAP-R) S. mitis/oralis strain (351-D10) revealed differences in glucose catabolism relative to its DAP-susceptible (DAP-S) parental strain, 351. Metabolic changes associated with the transition to this DAP-R phenotype suggested that inhibiting glycolysis could alter DAP susceptibility. In addition, the strong reliance of S. mitis/oralis on glycolysis for energy and biosynthetic intermediates suggested that inhibiting glycolysis would adversely affect growth and biomass accumulation. To test these hypotheses, we used the lactate dehydrogenase inhibitor oxamic acid (OXA) to assess its efficacy against DAP-S S. mitis/oralis strain 351 during DAP exposures in vitro and ex vivo. As expected, OXA was growth inhibitory to S. mitis/oralis in a dose-dependent manner in vitro; however, it did not alter in vitro DAP susceptibility profiles. In contrast, OXA did prevent the emergence of DAP-R in an ex vivo model of simulated endocardial vegetations. These data suggest that metabolic inhibitors directed against this fermentative bacterium with limited metabolic capabilities could enhance killing and potentially forestall the emergence of DAP resistance.

Heat, cold, acid, and bile salt induced differential proteomic responses of a novel potential probiotic Lactococcus garvieae C47 isolated from camel milk.

Probiotics encounter various stresses during food processing and digestion. This study evaluated the differential proteomic responses of a newly identified potential probiotic lactic acid bacteria, Lactococcus garvieae, isolated from camel milk. Lc. garvieae C47 was exposed to heat, cold, acid, and bile conditions, and stress-responsive proteins were identified. The proteomic analysis was done using 2D-IEF SDS PAGE and nano-LC-MS/MS. Out of 91 differentially expressed proteins, 20 upregulated and 27 downregulated proteins were shared among the stresses. The multivariate data analysis revealed abundance of elongation factor Ts (spot C42), uridine phosphorylase, fructose-bisphosphate aldolase, peptidase T, cobalt ECF transporter T component CbiQ, UDP-N-acetylmuramate-l-alanine ligase, uncharacterized protein, aspartokinase, chaperone protein DnaK, IGP synthase cyclase subunit, probable nicotinate-nucleotide adenylyltransferase, NADH-quinone oxidoreductase, holo-[acyl-carrier-protein] synthase, l-lactate dehydrogenase, and uncharacterized protein. The maximum number of differentially expressed proteins belonged to carbohydrate and protein metabolism, which indicates Lc. garvieae shifts towards growth and energy metabolism for resistance against stress conditions.

Systematic review and meta-analysis of long-term oncological outcomes of lateral lymph node dissection for metastatic nodes after neoadjuvant chemoradiotherapy in rectal cancer.

BACKGROUND: Standard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). In recent years, there is growing interest in performing an additional lateral lymph node dissection (LLND). The aim of this systematic review and meta-analysis was to investigate long-term oncological outcomes of nCRT followed by TME with or without LLND in patients with pre-treatment metastatic LLNs. METHODS: PubMed, Ovid MEDLINE, Embase, Cochrane Library and Clinicaltrials.gov were searched to identify comparative studies reporting long-term oncological outcomes in pre-treatment metastatic LLNs of nCRT followed by TME and LLND (LLND+) vs. nCRT followed by TME only (LLND-). Newcastle-Ottawa risk-of-bias scale was used. Outcomes of interest included local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Summary meta-analysis of aggregate outcomes was performed. RESULTS: Seven studies, including 946 patients, were analysed. One (1/7) study was of good-quality after risk-of-bias analysis. Five-year LR rates after LLND+ were reduced (range 3-15%) compared to LLND- (11-27%; RR = 0.40, 95%CI [0.25-0.62], p < 0.0001). Five-year DFS was not significantly different after LLND+ (range 61-78% vs. 46-79% for LLND-; RR = 0.72, 95%CI [0.51-1.02], p = 0.143), and neither was five-year OS (range 69-91% vs. 72-80%; RR = 0.72, 95%CI [0.45-1.14], p = 0.163). CONCLUSION: In rectal cancers with pre-treatment metastatic LLNs, nCRT followed by an additional LLND during TME reduces local recurrence risk, but does not impact disease-free or overall survival. Due to the low quality of current data, large prospective studies will be required to further determine the value of LLND.

A snapshot of intraoperative conditions to predict prolonged postoperative ileus after colorectal surgery.

BACKGROUND: The cause of prolonged postoperative ileus (PPOI) is multifactorial. The influence of preoperative factors on PPOI has been well documented, but little is known about the impact of intraoperative conditions. The aim of this study was to investigate the influence of intraoperative factors on PPOI in patients undergoing colorectal surgery. METHODS: The LekCheck study database of the Colorectal Unit at the Royal Adelaide Hospital was analysed. Per patient, over 60 data points were prospectively collected between March 2018 and July 2020. Intraoperative data were collected in theatre during a one-off snapshot measure. Univariate and multivariable logistic regression analyses were performed. RESULTS: Data of 336 patients were included. The median age was 66 years and 58.3% were male. Ninety-three patients (27.7%) developed PPOI. Univariate analysis identified the following intraoperative variables as risk-factors of PPOI: greater volumes of intraoperative IV fluid administration (464 versus 415 mL/h for those without PPOI; p = 0.04), side-to-side anastomosis orientation (53.8 versus 41.2%; p = 0.04) and increased perioperative opioid use (6.73 versus 4.11 mg/kg morphine equivalents for patients with and without PPOI, respectively; p = 0.02). Upon multivariable analysis, increased perioperative opioid use remained significant (p = 0.05), as well as the preoperative factors anticoagulation use (p = 0.04) and higher levels of serum total protein (p = 0.02). CONCLUSION: This study suggests that intraoperative factors may also contribute to the development of PPOI, but this could not be confirmed in the multivariate analysis. Further studies including larger patient numbers will be required to determine the impact of intraoperative conditions on the development of PPOI.

Interstitial cystitis/bladder pain syndrome (IC/BPS): Single-center 20 year experience and treatment results in India.

OBJECTIVES: Interstitial cystitis/bladder pain syndrome (IC/BPS) is an enigmatic disease that is difficult to treat. Even among physicians, the prevalent belief is that patients do not improve over time. In this study, we retrospectively reviewed our experience and treatment results for patients diagnosed with IC/BPS at our clinic in India over the past 20 years. MATERIALS AND METHODS: Three hundred and eighty IC/BPS patients diagnosed between January 2001 and December 2020 were included. Patients underwent cystoscopy and hydrodistension and were treated with oral drugs, intravesical instillations, and surgery as needed. From January 2021 to June 2021, all patients were contacted by telephone. RESULTS: The study had 380 participants, but only 231 could be contacted for analysis. Follow-up averaged 6.37 years and the median was 14 years. Eighteen percent showed no improvement, 2% showed a slight improvement on Global Response Assessment (GRA) questionnaire and were considered nonresponders (NR). Yet, 67% reported notable improvements, and 13% moderate improvements, all of which make up 80% responders (R). In 11 patients who were operated on for ileocystoplasty, 9 showed significant improvements. In addition, three patients developed Urothelial Malignancy. Pregnancy did not affect the disease in any way. CONCLUSIONS: Long-term results have been encouraging for IC/BPS patients. Unfortunately, Hunner's lesions patients need a more intensive treatment regimen. Re-evaluation with cystoscopy is recommended in NR. In spite of good results of surgery in our series, it is best to perform surgery only as a last resort.

Complete genome analysis of African swine fever virus isolated from domestic pigs during the first ASF outbreaks in India.

African swine fever (ASF), considered as the most dreadful swine disease due to its very high mortality, emerged in India in 2020. The complete genome analysis of ASF viruses isolated during the first outbreaks in India showed a few unique non-synonymous mutations in MGF 369-11L, MGF 505-4R, K205R and B263R genes. Frame shifts in the protein coding sequences were observed in DP60R, ASFV-G_ACD 00190, MGF 110-10-L-MGF110-14L fusion, MGF 360-14L and I267L genes of Indian ASF viruses as compared to ASFV/Georgia/2007. Complete genome based phylogenetic analysis of p72-genotype-II viruses showed the clustering of Indian isolates with ASFV/Wuhan/2019 in a separate clade. Phylogenetic analysis of concatenated sequences of 14 open reading frames (ORF) having single nucleotide polymorphisms (SNP) showed distinct grouping of Indian ASFVs with other Asian ASFVs. This is the first complete genome characterization of ASF viruses isolated from domestic pigs in India. The results indicate that number of Tandem Repeat Sequence (TRS) in the intergenic region between I73R and I329L genes, and the 14 ORFs with SNP reported in this study could be the genetic determinants to differentiate the closely related p72-genotype II viruses circulating in Asia.

Risk Nomogram Does Not Predict Anastomotic Leakage After Colon Surgery Accurately: Results of the Multi-center LekCheck Study.

PURPOSE: Anastomotic leakage (AL) is a dreaded complication after colorectal surgery. Preoperatively identifying high-risk patients can help to reduce the incidence of this complication. For this reason, AL risk nomograms have been developed. The objective of this study was to test the AL risk nomogram developed by Frasson, et al. for validity and to identify risk-factors for AL. METHODS: From the international multi-center LekCheck study database, patients who underwent colonic surgery with the formation of an anastomosis were included. Data were prospectively collected between 2016 and 2019 at 14 hospitals. Univariate and multivariable regression analyses, and area under receiver operating characteristic curve analysis (AUROC) were performed. RESULTS: A total of 643 patients were included. The median age was 70 years and 51% were male. The majority underwent surgery for malignancies (80.7%). The overall AL rate was 9.2%. The risk nomogram was not predictive for AL in the population tested (AUROC 0.572). Low preoperative haemoglobin (p = 0.006), intraoperative hypothermia (p = 0.02), contamination of the operative field (p = 0.004), and use of epidural analgesia (p = 0.02) were independent risk-factors for AL. CONCLUSION: The AL risk nomogram could not be validated using the international LekCheck study database. In the future, intraoperative predictive factors for AL, as identified in this study, should also be included in AL risk predictors.

Splenic artery embolization improves outcomes and decreases the length of stay in hemodynamically stable blunt splenic injuries - A level 1 Australian Trauma centre experience.

BACKGROUND: Splenic injuries are the most common visceral injury following blunt abdominal trauma. Increasingly, non-operative management (NOM) and the use of adjunctive splenic angioembolization (ASE) is favoured over operative management (OM) for the hemodynamically stable patient. However, clinical predictors for successful NOM, particularly the role of ASE as an adjunct, remain poorly defined. This study aims to evaluate the outcomes of patients undergoing ASE vs NOM. METHODS: A retrospective clinical audit was performed of all patients admitted with blunt splenic injury (BSI) from January 2005 to January 2018 at the Royal Adelaide Hospital. The primary outcome was ASE or NOM failure rate. Secondary outcomes were grade of splenic injury, Injury Severity Score (ISS), length of hospital stay (LOS), and delayed OM or re-angioembolization rates. RESULTS: Of 208 patients with BSI, 60 (29%) underwent OM, 54 (26%) ASE, and 94 (45%) NOM only. Patients were predominantly male 165 (79%), with a median age of 33 (IQR 24-51) years. The median ISS was 29 (20-38). There was no difference in the overall success rates for each modality of primary management (48 (89%) ASE vs 77 (82%) NOM, p = 0.374), though patients managed with ASE were older (38 vs 30 years, p = 0.029), had higher grade of splenic injury (grade ≥ IV 42 (78%) vs 8 (8.5%), p<0.001), with increased rates of haemo-peritoneum (46 (85%) vs 51 (54%), p<0.001) and contrast blush (42 (78%) vs 2 (2%), p<0.001). However, for grade III splenic injury, patients managed with ASE had a trend towards better outcome with no failures when compared to the NOM group (0 (0%) vs 8 (35%), p = 0.070) with a significant reduction in LOS (7.2 vs 10.8 days, p = 0.042). Furthermore, the ASE group overall had a significantly shorter LOS compared to the NOM group (10.0 vs 16.0 days, p<0.001). CONCLUSION: ASE as an adjunct to NOM significantly reduces the length of stay in BSI patients and is most successful in managing AAST grade III injuries.

Malignant Features in Pretreatment Metastatic Lateral Lymph Nodes in Locally Advanced Low Rectal Cancer Predict Distant Metastases.

INTRODUCTION: Pretreatment enlarged lateral lymph nodes (LLN) in patients with locally advanced low rectal cancer are predictive for local recurrences after neoadjuvant (chemo)radiotherapy (n(C)RT) followed by total mesorectal excision (TME). Not much is known of the impact on oncological outcomes when in addition malignant features are present in enlarged LLN. PATIENTS AND METHODS: A multicenter retrospective cohort study was conducted at five tertiary referral centers in the Netherlands and Australia. All patients were diagnosed with locally advanced low rectal cancer with LLN on pretreatment magnetic resonance imaging (MRI) and underwent n(C)RT followed by TME. LLN were considered enlarged with a short axis of ≥ 5 mm. Malignant features were defined as nodes with internal heterogeneity and/or border irregularity. Outcomes of interest were local recurrence-free survival (LRFS), distant metastatic-free survival (DMFS), and overall survival (OS). RESULTS: Out of 115 patients, the majority was male (75%) and the median age was 64 years (range 26-85 years). Median pretreatment LLN short axis was 7 mm (range 5-28 mm), and 60 patients (52%) had malignant features. After a median follow-up of 47 months, patients with larger LLN (7 + mm) had a worse LRFS (p = 0.01) but no difference in DMFS (p = 0.37) and OS (p = 0.54) compared with patients with smaller LLN (5-6 mm). LLN patients with malignant features had no difference in LRFS (p = 0.20) but worse DMFS (p = 0.004) and OS (p = 0.006) compared with patients without malignant features in the LLN. Cox regression analysis identified LLN short axis as an independent factor for LR. Malignant features in LLN were an independent factor for DMFS. CONCLUSION: The current study suggests that pretreatment enlarged LLN that also harbor malignant features are predictive of a worse DMFS. More studies will be required to further explore the role of malignant features in LLN.