Cohort study of long-term survival and recurrence patterns following operative management of colorectal liver metastasis - is follow-up beyond 5 years warranted?

AIMS: To evaluate the patterns of overall survival (OS) and recurrence following surgical resection of colorectal liver metastases (CRLM). METHODS: In compliance with STROCSS guideline, a single-centre retrospective cohort study was conducted. All consecutive patients undergoing resection of CRLM between 2003 and 2019 were considered eligible for inclusion. The outcome measures included OS, recurrence-free survival (RFS), recurrence rate, time to recurrence (TTR) and longest TTR. Statistical analyses included simple descriptive statistics and Kaplan-Meier survival statistics. RESULTS: We included 486 liver resections in 472 patients. The estimated median OS and RFS were 5.1 years and 3.1 years, respectively. The probability of 1-year, 3-year, 5-year and 10-year OS was 93%, 69%, 50% and 34%, respectively. The probability of 1-year, 3-year, 5-year and 10-year RFS was 81%, 50%, 34% and 33%, respectively. Recurrence occurred in 56% (271/486) of patients, and the median TTR was 1.6 years (IQR: 0.8-2.7) with longest TTR of 4.8 years. Although there were no recurrences in the 66 patients that entered the 6th year, the 95% CI for true rate of recurrence in the population given these data is 0-5.4%. CONCLUSIONS: Our results suggest that recurrences that occur after operative management of CRLM are almost certain to occur within the first 5 years even for patients surviving longer than 5 years. This does not disprove the requirement for follow up beyond 5 years. However, based on this data, we have altered our follow up from 10 to 6 years. The need for the 6th year of follow up will be reassessed in light of further observations.

Bifurcated binding of the OmpF receptor underpins import of the bacteriocin colicin N into Escherichia coli.

Colicins are Escherichia coli-specific bacteriocins that translocate across the outer bacterial membrane by a poorly understood mechanism. Group A colicins typically parasitize the proton-motive force-linked Tol system in the inner membrane via porins after first binding an outer membrane protein receptor. Recent studies have suggested that the pore-forming group A colicin N (ColN) instead uses lipopolysaccharide as a receptor. Contrary to this prevailing view, using diffusion-precipitation assays, native state MS, isothermal titration calorimetry, single-channel conductance measurements in planar lipid bilayers, and in vivo fluorescence imaging, we demonstrate here that ColN uses OmpF both as its receptor and translocator. This dual function is achieved by ColN having multiple distinct OmpF-binding sites, one located within its central globular domain and another within its disordered N terminus. We observed that the ColN globular domain associates with the extracellular surface of OmpF and that lipopolysaccharide (LPS) enhances this binding. Approximately 90 amino acids of ColN then translocate through the porin, enabling the ColN N terminus to localize within the lumen of an OmpF subunit from the periplasmic side of the membrane, a binding mode reminiscent of that observed for the nuclease colicin E9. We conclude that bifurcated engagement of porins is intrinsic to the import mechanism of group A colicins.

TGF-ß-dependent active demethylation and expression of the p15ink4b tumor suppressor are impaired by the ZNF217/CoREST complex.

In this study we examine the mechanisms of dynamic DNA methylation of the p15(ink4b) tumor suppressor gene. Using conventional ChIP and ChiPseq, we identify the p15(ink4b) promoter as a target for the ZNF217 oncogene, the CoREST complex, and DNMT3A. Treatment of cells with TGF-ß triggers active demethylation involving loss of ZNF217/CoREST/DNMT3A and the corecruitment of SMAD2/3, CBP, and the DNA glycosylase TDG. Knockdown of TDG, or its functional homolog MBD4, prevents TGF-ß-dependent demethylation of p15(ink4b). DNA immunoprecipitation of 5mC and 5hmC indicates that 5mC undergoes conversion to 5hmC prior to activation of p15(ink4b). Remarkably, overexpression of ZNF217 inhibits active demethylation and expression of the p15(ink4b) gene by preventing recruitment of SMAD2/3 and TDG. These findings suggest that active demethylation is essential for regulating a subset of TGF-ß-dependent genes. Importantly, disruption of active demethylation by the ZNF217 oncogene may be a paradigm for other oncogenic signals on DNA methylation dynamics.

Synthesis of Spirocyclic 1-Pyrrolines from Nitrones and Arynes through a Dearomative [3,3']-Sigmatropic Rearrangement.

A dearomative [3,3']-sigmatropic rearrangement that converts N-alkenylbenzisoxazolines into spirocyclic pyrroline cyclohexadienones has been developed by using the dipolar cycloaddition of an N-alkenylnitrone and an aryne to access these unusual transient rearrangement precursors. This cascade reaction affords spirocyclic pyrrolines that are inaccessible through dipolar cycloadditions of exocyclic cyclohexenones and provides a fundamentally new approach to novel spirocyclic pyrroline and pyrrolidine motifs that are common scaffolds in biologically-active molecules. Diastereoselective functionalization processes have also been explored to demonstrate the divergent synthetic utility of the unsaturated spirocyclic products.

Obesity and intensive staffing needs of nursing home residents.

The objective of this study is to examine how increasing body mass index (BMI) among nursing home residents affects the amount of staffing assistance needed for activities of daily living (ADL). We analyzed 1,627,141 US nursing home residents reported in the 2013 Minimum Data Set in seven BMI categories, from underweight (BMI < 18.5 kg/m2) to obesity Class IIIB (≥50 kg/m2). Logistic regression models estimated the odds of nursing home-reported need for extensive (≥2 staff member) assistance needed for ADLs. The adjusted odds increased from 1.07 (95% Confidence Interval (95%CI) 1.06-1.08) for Class I, 1.16 (95%CI 1.14-1.17) for Class II, 1.33 (95%CI 1.31-1.35) for Class IIIA, and 1.90 (95%CI 1.86-1.95) for Class IIIB obesity residents compared to residents of normal weight. As a nursing home resident's BMI increases, especially for BMI ≥40 kg/m2, the need for extensive staffing assistance with ADLs also increases substantially.

Minimally invasive versus open central pancreatectomy: A systematic review and meta-analysis.

To compare the procedural outcomes of minimally invasive and open central pancreatectomy. A systematic review in compliance with PRISMA statement standards was conducted to identify and analyze studies comparing the procedural outcomes of minimally invasive (laparoscopic or robotic) central pancreatectomy with the open approach. Random effects modeling using intention to treat data, and individual patient as unit of analysis, was used for analyses. Seven comparative studies including 289 patients were included. The two groups were comparable in terms of baseline characteristics. The minimally invasive approach was associated with less intraoperative blood loss (mean difference [MD]: -153.13 mL, p = 0.0004); however, this did not translate into less need for blood transfusion (odds ratio [OR]: 0.30, p = 0.06). The minimally invasive approach resulted in less grade B-C postoperative pancreatic fistula (OR: 0.54, p = 0.03); this did not remain consistent through sensitivity analyses. There was no difference between the two approaches in operative time (MD: 60.17 minutes, p = 0.31), Clavien-Dindo ≥ 3 complications (OR: 1.11, p = 0.78), postoperative mortality (risk difference: -0.00, p = 0.81), and length of stay in hospital (MD: -3.77 days, p = 0.08). Minimally invasive central pancreatectomy may be as safe as the open approach; however, whether it confers advantage over the open approach remains the subject of debate. Type 2 error is a possibility, hence adequately powered studies are required for definite conclusions; future studies may use our data for power analysis.

Community partnerships are fundamental to ethical ancient DNA research.

The ethics of the scientific study of Ancestors has long been debated by archaeologists, bioanthropologists, and, more recently, ancient DNA (aDNA) researchers. This article responds to the article "Ethics of DNA research on human remains: five globally applicable guidelines" published in 2021 in Nature by a large group of aDNA researchers and collaborators. We argue that these guidelines do not sufficiently consider the interests of community stakeholders, including descendant communities and communities with potential, but yet unestablished, ties to Ancestors. We focus on three main areas of concern with the guidelines. First is the false separation of "scientific" and "community" concerns and the consistent privileging of researcher perspectives over those of community members. Second, the commitment of the guidelines' authors to open data ignores the principles and practice of Indigenous Data Sovereignty. Further, the authors argue that involving community members in decisions about publication and data sharing is unethical. We argue that excluding community perspectives on "ethical" grounds is convenient for researchers, but it is not, in fact, ethical. Third, we stress the risks of not consulting communities that have established or potential ties to Ancestors, using two recent examples from the literature. Ancient DNA researchers cannot focus on the lowest common denominator of research practice, the bare minimum that is legally necessary. Instead, they should be leading multidisciplinary efforts to create processes to ensure communities from all regions of the globe are identified and engaged in research that affects them. This will often present challenges, but we see these challenges as part of the research, rather than a distraction from the scientific endeavor. If a research team does not have the capacity to meaningfully engage communities, questions must be asked about the value and benefit of their research.

Myocardial infarction secondary to contrast agent. Contrast effect or type II Kounis syndrome?

The diagnostic administration of contrast agents has been increased recently in various fields, including coronary angiography, but reports of coronary artery spasm caused by contrast agents are rare. However, myocardial infarction following administration of nonionic contrast agents has not been reported, as far as we are aware. Herein, we described a case of acute anterior myocardial infarction induced by the contrast agent iopromide (Ultravist). We also discussed the possible reasons for this situation.

A community-university run conference as a catalyst for addressing health disparities in an urban community.

The African American population of Buffalo, New York experiences striking race-based health disparities due to adverse social determinants of health. A team of community leaders and university faculty determined that a community dialogue was needed to focus research and advocacy on the root causes of these disparities. In response, we organized the annual Igniting Hope conference series that has become the premier conference on health disparities in the region. The series, now supported by an R13 conference grant from NCATS, has been held four times (2018-2021) and has attracted community members, community leaders, university faculty, and trainees. The agenda includes talks by national leaders and breakout/working groups that led to a new state law that has reduced disproportionate traffic-ticketing and drivers' license suspensions in Black neighborhoods; mitigation of the disproportionate COVID-19 fatalities in Black communities; and the launching of a university-supported institute. We describe the key elements of success for a conference series designed by a community-university partnership to catalyze initiatives that are having an impact on social determinants of health in Buffalo.

Robust High-Throughput Phenotyping with Deep Segmentation Enabled by a Web-Based Annotator.

The abilities of plant biologists and breeders to characterize the genetic basis of physiological traits are limited by their abilities to obtain quantitative data representing precise details of trait variation, and particularly to collect this data at a high-throughput scale with low cost. Although deep learning methods have demonstrated unprecedented potential to automate plant phenotyping, these methods commonly rely on large training sets that can be time-consuming to generate. Intelligent algorithms have therefore been proposed to enhance the productivity of these annotations and reduce human efforts. We propose a high-throughput phenotyping system which features a Graphical User Interface (GUI) and a novel interactive segmentation algorithm: Semantic-Guided Interactive Object Segmentation (SGIOS). By providing a user-friendly interface and intelligent assistance with annotation, this system offers potential to streamline and accelerate the generation of training sets, reducing the effort required by the user. Our evaluation shows that our proposed SGIOS model requires fewer user inputs compared to the state-of-art models for interactive segmentation. As a case study of the use of the GUI applied for genetic discovery in plants, we present an example of results from a preliminary genome-wide association study (GWAS) of in planta regeneration in Populus trichocarpa (poplar). We further demonstrate that the inclusion of a semantic prior map with SGIOS can accelerate the training process for future GWAS, using a sample of a dataset extracted from a poplar GWAS of in vitro regeneration. The capabilities of our phenotyping system surpass those of unassisted humans to rapidly and precisely phenotype our traits of interest. The scalability of this system enables large-scale phenomic screens that would otherwise be time-prohibitive, thereby providing increased power for GWAS, mutant screens, and other studies relying on large sample sizes to characterize the genetic basis of trait variation. Our user-friendly system can be used by researchers lacking a computational background, thus helping to democratize the use of deep segmentation as a tool for plant phenotyping.

Molecular insights and future frontiers in cell photosensitization for solar-driven CO2 conversion.

The conversion of CO2 to value-added products powered with solar energy is an ideal solution to establishing a closed carbon cycle. Combining microorganisms with light-harvesting nanomaterials into photosynthetic biohybrid systems (PBSs) presents an approach to reaching this solution. Metabolic pathways precisely evolved for CO2 fixation selectively and reliably generate products. Nanomaterials harvest solar light and biocompatibly associate with microorganisms owing to similar lengths scales. Although this is a nascent field, a variety of approaches have been implemented encompassing different microorganisms and nanomaterials. To advance the field in an impactful manner, it is paramount to understand the molecular underpinnings of PBSs. In this perspective, we highlight studies inspecting charge uptake pathways and singularities in photosensitized cells. We discuss further analyses to more completely elucidate these constructs, and we focus on criteria to be met for designing photosensitizing nanomaterials. As a result, we advocate for the pairing of microorganisms with naturally occurring and highly biocompatible mineral-based semiconductor nanomaterials.

How successful is liver resection for colorectal cancer liver metastases in patients over 75 years old?

BACKGROUNDS/AIMS: As populations age, an increased incidence of colorectal cancer will generate an increase in colorectal cancer liver metastases (CRLM). In order to guide treatment decisions, this study aimed to identify the contemporary complication rates of elderly patients undergoing liver resection for CRLM in a, centralised, UK centre. METHODS: All patients undergoing operative procedures for CRLM between January 2013 and January 2019 were included. Patient, tumour and operative data were analysed, including the prognostic marker; tumour burden score. RESULTS: 339 operations were performed on 289 consecutive patients with CRLM (272 patients ＜75 years old, 67 patients ≥75 years old). Median age was 66 years (range 20-93). There was no difference in major complication rates between the two age cohorts (6.65 vs. 6.0%, p=0.847) or operative mortality (1.1% vs. 1.4%, p=0.794). Younger patients had higher R1 resection rates (20.4% vs. 4.5%, p=0.002) and post-operative chemotherapy rates (60.3% vs. 35.8%, p< 0.001). The 1, 3 and 5-year OS was 90.2%, 70.5% and 52.3% respectively, median 70 months, with no difference between age cohorts (p=0.772). Tumour Burden score and operation type were independent predictors of overall survival. CONCLUSIONS: Liver resection for CRLM in patients 75 years and older is feasible, safe and confers a similar 5-year survival rate to younger patients. The current outcomes from surgery are better than historical datasets.

Kounis Syndrome Associated With Takotsubo Syndrome in an Adolescent With Peutz-Jeghers Syndrome.

We describe the case of a 15-year-old female patient with Peutz-Jeghers syndrome who presented with vomiting and abdominal pain secondary to ileoileal invagination. Initial analgesic treatment was not effective, and subsequent tramadol infusion resulted in clinical manifestations compatible with Kounis and Takotsubo syndromes. However, the patient had an excellent recovery. (Level of Difficulty: Advanced.).

Organizational and Geographic Nursing Home Characteristics Associated With Increasing Prevalence of Resident Obesity in the United States.

Nursing home resident obesity increases the complexity of nursing care, and nursing homes report avoiding residents with obesity when choosing which prospective residents to accept. The objective of this study was to examine the associations between nursing home obesity prevalence rate and nursing home organizational, staffing, resident, and geographic factors within a profit maximization framework. The study cohort included U.S. Centers for Medicare and Medicaid Services data from U.S. nursing homes in 2013. Study findings supported hypothesized associations between obesity prevalence rate and higher occupancy, higher bed capacity, and multi-facility affiliation, but findings did not support a relationship between obesity prevalence rate and for-profit status.

Anaphylactic cardiovascular collapse manifesting as myocardial infarction following salad consumption. A case of Kounis variant type I syndrome.

Anaphylactic cardiovascular events constitute an underrated cause of medical emergencies in hospitalized patients. Coronary arteries and myocardium are targeted by anaphylactic mediators leading to acute coronary syndrome and imminent cardiovascular collapse. Early diagnosis and high clinical suspicion are required to secure prompt life-saving treatment in these cases. However, physicians of both Cardiology and Internal Medicine Departments are not familiar with this condition. Recently, we diagnosed and treated a case of anaphylactic cardiovascular collapse manifesting as acute myocardial infarction following salad consumption. Notably, Kounis anaphylaxis-associated acute coronary syndrome is a rare cause of ST segment elevation myocardial infarction with normal or diseased coronary arteries. We recommend that Kounis syndrome and its variants should be taken into consideration in the differential diagnosis of ischemic heart disease in patients with signs of allergic reaction and/or medical history of previous allergic reactions, who experience acute coronary syndrome after exposure to certain environmental stimuli.

Obesity and Nursing Home Care in the United States: A Systematic Review.

BACKGROUND AND OBJECTIVES: Obesity is increasing among people residing in nursing homes, and resident obesity substantially affects services needed, equipment and facilities provided, and morbidity in this setting. The purpose of this article is to describe the scope and depth of evidence regarding the impact of obesity among nursing home residents in the United States. RESEARCH DESIGN AND METHODS: A systematic literature review was performed in PubMed, EMBASE, CINAHL, and Web of Science databases as well as additional hand-searched documents. Included articles were published from 1997 to March 2017. The characteristics and content of the included articles were systematically reviewed and reported. RESULTS: Twenty-eight studies met inclusion criteria for review. The median study size was 636 residents (interquartile range 40-11,248); 18 (64%) studies were retrospective and 10 (36%) were prospective in nature. Ten (36%) studies examined medical and functional morbidity, 10 (36%) examined health system effects, and 5 (18%) examined the risk of admission to nursing homes. Most studies found that obesity poses serious issues to resident health and the provision of health care, as well as broad health system and nursing challenges in the provision of high-quality nursing home care and services. DISCUSSION AND IMPLICATIONS: Although obesity affects about one in four nursing home residents in the United States, relatively limited evidence exists on the complex challenges of obesity for their residents and their care. A continued focus on resident quality of life, health system improvement, and nursing best practices for properly caring for individuals with obesity is needed.

Effect of stochastic resonance on proprioception and kinesthesia in anterior cruciate ligament reconstructed patients.

Low amplitude mechanical noise vibration has been shown to improve somatosensory acuity in various clinical groups with comparable deficiencies through a phenomenon known as Stochastic Resonance (SR). This technology showed promising outcomes in improving somatosensory acuity in other clinical patients (e.g., Parkinson's disease and osteoarthritis). Some degree of chronic somatosensory deficiency in the knee has been reported following anterior cruciate ligament (ACL) reconstruction surgery. In this study, the effect of the SR phenomenon on improving knee somatosensory acuity (proprioception and kinesthesia) in female ACL reconstructed (ACLR) participants (n = 19) was tested at three months post-surgery, and the results were compared to healthy controls (n = 28). Proprioception was quantified by the measure of joint position sense (JPS) and kinesthesia with the threshold to detection of passive movement (TDPM). The results based on the statistical analysis demonstrated an overall difference between the somatosensory acuity in the ACLR limb compared to healthy controls (p = 0.007). A larger TDPM was observed in the ACLR limb compared to the healthy controls (p = 0.002). However, the JPS between the ACLR and healthy limbs were not statistically significantly different (p = 0.365). SR significantly improved JPS (p = 0.006) while the effect was more pronounced in the ACLR cohort. The effect on the TDPM did not reach statistical significance (p = 0.681) in either group. In conclusion, deficient kinesthesia in the ACLR limb was observed at three months post-surgery. Also, the positive effects of SR on somatosensory acuity in the ACL reconstructed group warrant further investigation into the use of this phenomenon to improve proprioception in ACLR and healthy groups.

Laparoscopic Left Pancreatectomy in the United Kingdom: Analysis of a Six-Year Experience in a Single Tertiary Center.

OBJECTIVES: Laparoscopic techniques have been slow to establish a role in pancreatic surgery. Worldwide, laparoscopic left pancreatectomy (LLP) is gaining in popularity; however, there remains little published data from the United Kingdom.We aimed to evaluate the results of LLP performed in a single UK pancreatic unit. METHODS: Patients undergoing LLP for lesions in the body and tail of the pancreas between April 2009 and April 2015 were identified. Patient records were reviewed retrospectively. RESULTS: Laparoscopic left pancreatectomy was performed on 46 patients, median age, 62 years (range, 19-84). The spleen was preserved in 27 patients (93% of planned), and 6 (13%) operations were converted to open. The overall morbidity rate was 39%; 28 patients had no complications. Significant complications were seen in 7 (15%) patients; this included 3 pancreatic fistula (6.5%) and 1 mortality (2%). Median length of stay was 6 days (range, 3-28). Histology revealed 15 neuroendocrine tumors, 8 adenocarcinomas, 4 mucinous cystadenomas, 1 intraductal papillary mucinous neoplasm, 2 metastases, and 16 other benign pathologies. CONCLUSIONS: Laparoscopic pancreatic surgery has a low risk of significant complications. Our results offer encouragement to identify LLP as the gold standard approach for premalignant lesions. Further work should clarify the outcomes for malignant lesions.