Improved survival with immunotherapy for microsatellite unstable colorectal cancer with peritoneal metastases.

BACKGROUND: KEYNOTE-177 demonstrated that immunotherapy was superior to chemotherapy for microsatellite-instability-high (MSI-high) metastatic colorectal cancer. Colorectal cancer with peritoneal metastases (CRPM) has a poorer prognosis than other metastatic sites, with an unclear role of immunotherapy. We evaluated trends in immunotherapy use and overall survival (OS). METHODS: Patients with CRPM and MSI testing were identified in the National Cancer Database (2016-2020). We evaluated immunotherapy use by year and associated patient/hospital factors. OS was compared for immunotherapy versus chemotherapy, cytoreductive surgery (CRS), and immunotherapy plus CRS. RESULTS: Among 15 322 CRPM patients, 7072 (46.2%) patients had documented MSI testing, with 819 (11.6%) MSI-high. Ninety-eight MSI-high patients received immunotherapy alone (12.3%), increasing from 0% in 2016 to 19.1% in 2020 (p < 0.01). On multivariable analysis, only higher comorbidity was associated with immunotherapy (OR: 2.83 [1.22-6.52]). Two-year OS with immunotherapy versus chemotherapy was 64.2% versus 54.1% (p < 0.05). In patients receiving CRS plus systemic therapy (N = 96), 2-year OS was 68.4%. Among patients who underwent immunotherapy and CRS versus immunotherapy alone, 2-year OS was 80.0% versus 60.0% (p = 0.14). CONCLUSIONS: Immunotherapy was associated with significantly better survival compared to chemotherapy in MSI-high CRPM. Two-year OS with systemic + CRS was 68.4%. Despite its role in guiding treatment, MSI testing remains low for these patients.

Oncologic outcomes and survival of modern surgical approaches for gastric gastrointestinal stromal tumor (GIST).

BACKGROUND: Studies have demonstrated comparable outcomes between laparoscopic and open resection of gastrointestinal stromal tumor (GIST). We sought to compare outcomes among robotic, laparoscopic, and open resection of gastric GIST in the era of expanding minimally invasive surgery. METHODS: A retrospective analysis was performed of adult patients with gastric GIST undergoing definitive surgery using the National Cancer Database from 2010 to 2020, excluding cases converted to open. Patients were stratified into minimally invasive surgery (MIS), (combined robotic (R) and laparoscopic (L)), and open (O). Hospital length of stay (LOS), 30-day mortality, 90-day mortality, and margin status were assessed. Subgroup analysis was performed to evaluate outcomes between R and L cohorts. Entropy balancing was used to adjust for intergroup differences. Kaplan-Meier survival estimates were used to compare unadjusted 5-year survival. RESULTS: Of the 15,022 patients (R = 10.4%, L = 44.3%, O = 45.3%), 63.2% were stage I and 70.6% underwent partial gastrectomy. MIS approach was associated with shorter hospital LOS (ß: - 2.58; 95% CI: - 2.82 to - 2.33) and lower odds of 30-day (OR 0.45; 95% CI: 0.30-0.68) and 90-day mortality (OR 0.54; 95% CI: 0.39-0.74) compared to O. Likelihood of R0 resection similar between groups (OR 1.00; 95% CI: 0.88-1.14). Hospital LOS (ß: + 0.25; 95% CI: - 0.14-0.64), odds of 30-day (OR 0.99; 95% CI: 0.40-2.46) and 90-day mortality (OR 0.89; 95% CI: 0.47-1.70), and rate of R0 resection (OR 1.02; 95% CI: 0.82-1.27) were comparable between R and L cohorts. Compared to O, MIS approach was associated with improved 5-year OS (log rank p < 0.001). Overall survival was not significantly different between R and L (log rank p = 0.44). CONCLUSION: These findings suggest that MIS approach may be considered for resection of gastric GIST in select patients. Among patients receiving an MIS approach, the robotic technique can be considered an oncologically safe alternative to laparoscopic surgery.

Decreasing Utilization of Vaginal Hysterectomy in the United States: An Analysis by Candidacy for Vaginal Approach.

INTRODUCTION AND HYPOTHESIS: The objective was to assess trends in hysterectomy routes by patients who are likely and unlikely candidates for a vaginal approach. METHODS: We performed a retrospective cohort study of patients who underwent vaginal, abdominal, or laparoscopic/robotics-assisted laparoscopic hysterectomy between 2017 and 2020 using the National Surgical Quality Improvement Program database. Patients undergoing hysterectomy for a primary diagnosis of benign uterine pathology, dysplasia, abnormal uterine bleeding, or pelvic floor disorders were eligible for inclusion. Patients who were parous, had no history of pelvic or abdominal surgery, and had a uterine weight ≤ 280 g on pathology were considered likely candidates for vaginal hysterectomy based on an algorithm developed to guide the surgical approach. Average annual changes in the proportion of likely vaginal hysterectomy candidates and route of hysterectomy were assessed using logistic regression. RESULTS: Of the 77,829 patients meeting the inclusion criteria, 13,738 (17.6%) were likely vaginal hysterectomy candidates. Among likely vaginal hysterectomy candidates, the rate of vaginal hysterectomy was 34.5%, whereas among unlikely vaginal hysterectomy candidates, it was 14.1%. The overall vaginal hysterectomy rate decreased -1.2%/year (p < 0.01). This decreasing trend was nearly twice as rapid among likely vaginal hysterectomy candidates (-1.9%/year, p < .01) compared with unlikely vaginal hysterectomy candidates (-1.1%/year, P < 0.01); the difference in trends was statistically significant (p < 0.01). CONCLUSIONS: The rate of vaginal hysterectomy performed for eligible indications decreased between 2017 and 2020 in a national surgical registry. This negative trend was more pronounced among patients who were likely candidates for vaginal hysterectomy based on favorable parity, surgical history, and uterine weight.

Natural Recombination among Type I Restriction-Modification Systems Creates Diverse Genomic Methylation Patterns among Xylella fastidiosa Strains.

Xylella fastidiosa is an important bacterial plant pathogen causing high-consequence diseases in agricultural crops around the world. Although as a species X. fastidiosa can infect many host plants, there is significant variability between strains regarding virulence on specific host plant species and other traits. Natural competence and horizontal gene transfer are believed to occur frequently in X. fastidiosa and likely influence the evolution of this pathogen. However, some X. fastidiosa strains are difficult to manipulate genetically using standard transformation techniques. Several type I restriction-modification (R-M) systems are encoded in the X. fastidiosa genome, which may influence horizontal gene transfer and recombination. Type I R-M systems themselves may undergo recombination, exchanging target recognition domains (TRDs) between specificity subunits (hsdS) to generate novel alleles with new target specificities. In this study, several conserved type I R-M systems were compared across 129 X. fastidiosa genome assemblies representing all known subspecies and 32 sequence types. Forty-four unique TRDs were identified among 50 hsdS alleles, which are arrayed in 31 allele profiles that are generally conserved within a monophyletic cluster of strains. Inactivating mutations were identified in type I R-M systems of specific strains, showing heterogeneity in the complements of functional type I R-M systems across X. fastidiosa. Genomic DNA methylation patterns were characterized in 20 X. fastidiosa strains and associated with type I R-M system allele profiles. Overall, these data suggest hsdS genes recombine among Xylella strains and/or unknown donors, and the resulting TRD reassortment establishes differential epigenetic modifications across Xylella lineages. IMPORTANCE Economic impacts on agricultural production due to X. fastidiosa have been severe in the Americas, Europe, and parts of Asia. Despite a long history of research on this pathogen, certain fundamental questions regarding the biology, pathogenicity, and evolution of X. fastidiosa have still not been answered. Wide-scale whole-genome sequencing has begun to provide more insight into X. fastidiosa genetic diversity and horizontal gene transfer, but the mechanics of genomic recombination in natural settings and the extent to which this directly influences bacterial phenotypes such as plant host range are not well understood. Genome methylation is an important factor in horizontal gene transfer and bacterial recombination that has not been comprehensively studied in X. fastidiosa. This study characterizes methylation associated with type I restriction-modification systems across a wide range of X. fastidiosa strains and lays the groundwork for a better understanding of X. fastidiosa biology and evolution through epigenetics.

Organ donation by children in Australia, 2000-2019: impact of the 2009 National Reform Program. A population-based registry data study.

OBJECTIVES: To assess the impact of the 2009 National Reform Program for organ donation in Australia on the number and characteristics of organ donors under 16 years of age. DESIGN, SETTING, PARTICIPANTS: Retrospective observational time series study; analysis of Australia and New Zealand Organ Donation (ANZOD) registry data for all consented potential deceased organ donors under 16 years of age during 2000-2019, and of numbers of donors aged 16 years or more reported in ANZOD annual reports. MAIN OUTCOME MEASURES: Difference between 2000-2008 (pre-reform) and 2009-2019 (reform period) in annual organ donor rates (donors per million population), by age group (under 16 years, 16 years or more), reported as incidence rate ratio (IRR). SECONDARY OUTCOMES: Differences in child donor characteristics during 2000-2008 and 2009-2019. RESULTS: During 2000-2019, 400 children under 16 years of age were consented potential deceased organ donors, of whom 374 were actual deceased donors (94%): 146 during 2000-2008, 228 during 2009-2019. The median annual rate was 3.3 (interquartile range [IQR], 3.0-4.3) actual donors per million population during 2000-2008 and 4.2 (IQR, 3.6-5.2) donors per million population during 2009-2019 (IRR, 1.15; 95% confidence interval [CI], 0.93-1.42). In contrast, the difference between the two periods was statistically significant for donors aged 16 years or more, rising from 11.7 (IQR, 11.2-11.8) to 19.9 (IQR, 18.3-24.4) actual donors per million population (IRR, 1.75; 95% CI, 1.66-1.85). The median age of actual organ donors under 16 was similar during 2000-2008 (11 years; IQR, 7-14 years) and 2009-2019 (10 years; IQR, 4-14 years), as was the proportion of donors in this age group under 10 kg (2000-2008: four of 146, 3%; 2009-2019: 14 of 228, 6%). CONCLUSIONS: Despite its overall effect on organ donation rates, the National Reform Program was not effective in increasing the numbers of donors under 16 years of age. Relying on broad initiatives for adult donors may not be appropriate for achieving this aim.

Effect of reverse shoulder arthroplasty humeral component retroversion on acromial strain.

INTRODUCTION: Acromion and scapular spine stress fractures can be catastrophic complications following reverse shoulder arthroplasty (RSA). A variety of host, implant, and technical factors have been identified that increase the risk of this complication. The glenoid component in particular has been closely evaluated for its impact on rates of stress fractures following RSA. The goal of this biomechanical study is to evaluate if humeral stem version has an impact on acromion and scapular spine strain after RSA. METHODS: Eight cadaveric specimens were tested on a custom dynamic shoulder frame. Commercially available RSA components were implanted with the humeral component inserted in 0° of retroversion. Acromion and scapular spine strain were measured at 0°, 30°, and 60° of abduction using strain rosettes secured to the acromion and scapular spine in the typical locations for Levy type II and type III stress fractures, respectively. The humeral stem was then removed and reimplanted in 30° of retroversion and the measurements were repeated. Student t test was performed to analyze the relationship between humeral stem version and acromion and scapular spine strain at various abduction angles. RESULTS: Strain at the both the acromion and scapular spine were found to have no significant difference at any abduction angle when comparing 0° and 30° version of the humeral stem. With 0° and 30° versions pooled together, there is significantly lower acromion and scapular spine strain at 60° of abduction when compared to 0° of abduction (strain at 0° abduction - strain at 60° abduction: acromion 313.1 µêœª; P = .0409, Scapular spine 304.9 µêœª; P = .0407). There was no significant difference in strain at either location when comparing 0° of abduction to 30° of abduction and when comparing 30° of abduction to 60° of abduction. CONCLUSIONS: This biomechanical study found no significant difference in scapular spine and acromion strain after RSA when comparing variations in humeral stem version. There does appear to be lower strain at both the acromion and scapular spine at 60° of abduction when compared to 0° of abduction regardless of stem version.

Effects of long-term testosterone treatment on cardiovascular outcomes in men with hypogonadism: Rationale and design of the TRAVERSE study.

BACKGROUND: Testosterone exerts some effects on the cardiovascular system that could be considered beneficial; some other effects may potentially increase the risk of cardiovascular (CV) events. Neither the long-term efficacy nor safety of testosterone treatment has been studied in an adequately-powered randomized trial. METHODS: The Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) study is a randomized, double-blind, placebo-controlled, parallel group, non-inferiority, multicenter study. Eligible participants are men, 45 to 80 years, with serum testosterone concentration <300 ng/dL and hypogonadal symptoms, who have evidence pre-existing CV disease or increased risk of CV disease. Approximately 6,000 subjects will be randomized to either 1.62% transdermal testosterone gel or a matching placebo gel daily for an anticipated duration of up to 5 years. The primary outcome is CV safety defined by the major adverse CV event composite of nonfatal myocardial infarction, nonfatal stroke, or death due to CV causes. The trial will continue until at least 256 adjudicated major adverse CV event endpoints have occurred to assess whether the 95% (2-sided) upper confidence limit for a hazard ratio of 1.5 can be ruled out. Secondary endpoints include prostate safety defined as the incidence of adjudicated high grade prostate cancer and efficacy in domains of sexual function, bone fractures, depression, anemia, and diabetes. RESULTS: As of July 1, 2021, 5,076 subjects had been randomized. CONCLUSIONS: The TRAVERSE study will determine the CV safety and long-term efficacy of testosterone treatment in middle-aged and older men with hypogonadism with or at increased risk of CV disease.

PIPAC for the Treatment of Gynecologic and Gastrointestinal Peritoneal Metastases: Technical and Logistic Considerations of a Phase 1 Trial.

BACKGROUND: Peritoneal metastases (PM) from ovarian, gastric, appendiceal, or colorectal origin can be treated via cytoreductive surgery with or without the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) for selected patients. Unfortunately, not all patients are candidates for aggressive surgical debulking. For these patients, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) has emerged as an alternative method for intraperitoneal (IP) chemotherapy administration. This report presents the design and implementation of the first phase 1 trial to evaluate the safety and efficacy of PIPAC in the United States. METHODS: This is an ongoing prospective phase 1 clinical trial of PIPAC for patients who have histologically confirmed ovarian, uterine, gastric, appendiceal, or colorectal cancer with PM and have progressed to at least one evidence-based chemotherapeutic regimen. The trial has two clinical arms. The patients in arm 1 have gynecologic and gastric malignancies treated with IP cisplatin and doxorubicin, and the arm 2 patients have colorectal and appendiceal malignancies treated with intravenous fluorouracil and leucovorin followed by IP oxaliplatin. All the patients are monitored for dose-limiting toxicities and adverse events. RESULTS: Practical and technical considerations for the phase 1 PIPAC trial are presented. These considerations include patient selection, operating room setup, and technical details for successful aerosolized chemotherapy delivery. The phase 1 study results will be reported separately at completion of the trial. CONCLUSIONS: The PIPAC treatment is a feasible, minimally invasive approach that permits IP delivery of chemotherapy. Once completed, the ongoing phase 1 trial will help to provide safety and initial efficacy data.

Pilot study of a novel transmembranous electromyography device for assessment of oral cavity and oropharyngeal muscles.

INTRODUCTION/AIMS: Electromyography (EMG) can provide valuable insights into the pathophysiology of oropharyngeal muscles in various disease states, but the invasive nature of the conventional needle EMG (nEMG) has its limitations in this setting. We aimed to examine the inter-rater reliability (IRR) of a novel transmembranous EMG (tmEMG) sensor as a non-invasive technique for assessment of oral cavity and oropharyngeal muscles for neuromuscular pathology. METHODS: The study was a prospective, cohort, pilot study with blinded data analysis in healthy participants (n = 6), patients with moderate to severe obstructive sleep apnea (OSA) (n = 5) and bulbar amyotrophic lateral sclerosis (ALS) (n = 5). Each patient underwent sampling from bilateral palatoglossus (PG) and genioglossus (GG), using both tmEMG and nEMG. IRR was expressed as percentage agreement and prevalence-adjusted bias-adjusted kappa coefficient (PABAK). RESULTS: Substantial IRR was found for participants with ALS (81.6%, PABAK 0.63) and OSA (78.8%, PABAK 0.61), and in healthy participants (87.1%, PABAK 0.74). A better IRR was seen with tmEMG (95.7%, PABAK 0.92) than with nEMG (73.9%, PABAK 0.48) for healthy participants and also for those with OSA. Studies from GG had higher IRR than PG. Only one participant had a minor adverse event (sore throat). DISCUSSION: The current study shows that analysis of PG and GG in both healthy and disease states using tmEMG has high IRR compared with nEMG analysis. Further validation studies can be undertaken to test its utility in analysis of oral cavity and oropharyngeal muscles.

The 2020 Pandemics: Lessons Learned in Academic Surgery and Beyond.

2020 was a significant year because of the occurrence of two simultaneous public health crises: the coronavirus pandemic and the public health crisis of racism brought into the spotlight by the murder of George Floyd. The coronavirus pandemic has affected all aspects of health care, particularly the delivery of surgical care, surgical education, and academic productivity. The concomitant public health crisis of racism and health inequality during the viral pandemic highlighted opportunities for action to address gaps in surgical care and the delivery of public health services. At the 2021 Academic Surgical Congress Hot Topics session on flexibility and leadership, we also explored how our military surgeon colleagues can provide guidance in leadership during times of crisis. The following is a summary of the issues discussed during the session and reflections on the important lessons learned in academic surgery over the past year.

Death determination, organ donation and the importance of the Dead Donor Rule following withdrawal of life-sustaining treatment: a survey of community opinions.

BACKGROUND: Background: Organ donation (OD) following circulatory determination of death (DCDD) is an increasing source of transplant organs but little is known about community opinions on treatment withdrawal, determination of death and acceptance of OD in DCDD. AIMS: To determine attitudes on death determination in DCDD, the importance of patient choice in treatment withdrawal and OD agreement, and the importance of the 'Dead Donor Rule'. METHODS: Scenario-based online survey of 1017 members of the Australian general public. Mean levels of agreement across respondent's responses to statements were compared by repeated measures ANOVA. RESULTS: 54% (548) of respondents agreed that a DCDD scenario patient could be declared dead 2 minutes after circulatory standstill, however over 80% nonetheless agreed OD would be appropriate, including 77% (136/176) of those disagreeing with a 2-minute death declaration. 48% (484) supported OD even if it caused the patient's death. 75% (766) would accept relatively benign ante-mortem treatments administered to improve transplant outcomes. Over 70% supported a high quadriplegic patient's request to be allowed to die, with 61% (622) agreeing that he should be allowed to donate his organs under anaesthesia, but 60% (610) also agreed that he should first be declared dead. CONCLUSIONS: We found high levels of support for treatment withdrawal in severe brain injury and when requested by a quadriplegic patient. While there was variable agreement with the timing of death determination and with OD under anaesthesia, support for OD was high in both scenarios. For many people death determination prior to OD may not be of paramount importance.

Age-adjusted incidence rates of synchronous liver metastases for stage IV colorectal cancer compared by sex, race, and age group.

BACKGROUND: Reports on age-adjusted incidence rates of synchronous colorectal liver metastases (CRLM) among patients with stage IV colorectal cancer (CRC) are uncommon. This study presents in detail differences in CRLM incidence rates by sex, race, and age group. METHODS: Incidence rates were obtained for adults diagnosed with Stage IV CRC in the years 2010-2015 using SEER. The ratio of CRLM incidence to stage IV CRC incidence was used to calculate the rate ratio. RESULTS: Average age-adjusted CRLM incidence rate was 7.09 per 100,000 (95% CI, 6.93-7.26). CRLM incidence was higher at 8.68 (95% CI, 8.35-9.03) for males compared with 5.77 (95% CI, 5.64-5.90) for females. Highest incidence rate of 11.50 (95% CI, 10.43-11.76) was observed among Blacks. By age group the highest CRLM incidence was 24.42 (95% CI, 23.13-25.71) among adults age >75. The average rate ratio of CRLM to CRC incidence rate was 0.72 (95% CI, 0.71-0.73). CONCLUSION: Age-adjusted incidence rates of synchronous CRLM are higher for men, Blacks, and older patients. The risk ratio indicates that 72% of stage IV CRC cases are at risk of synchronous CRLM, although CRLM risk appears to decline with age.

A scoping review of the perceptions of death in the context of organ donation and transplantation.

BACKGROUND: Socio-cultural perceptions surrounding death have profoundly changed since the 1950s with development of modern intensive care and progress in solid organ transplantation. Despite broad support for organ transplantation, many fundamental concepts and practices including brain death, organ donation after circulatory death, and some antemortem interventions to prepare for transplantation continue to be challenged. Attitudes toward the ethical issues surrounding death and organ donation may influence support for and participation in organ donation but differences between and among diverse populations have not been studied. OBJECTIVES: In order to clarify attitudes toward brain death, organ donation after circulatory death and antemortem interventions in the context of organ donation, we conducted a scoping review of international English-language quantitative surveys in various populations. STUDY APPRAISAL: A search of literature up to October 2020 was performed, using multiple databases. After screening, 45 studies were found to meet pre-specified inclusion criteria. RESULTS: 32 studies examined attitudes to brain death, predominantly in healthcare professionals. In most, around 75% of respondents accepted brain death as equivalent to death of the person. Less common perspectives included equating death with irreversible coma and willingness to undertake organ donation even if it caused death. 14 studies examined attitudes to organ donation following circulatory death. Around half of respondents in most studies accepted that death could be confidently diagnosed after only 5 min of cardiorespiratory arrest. The predominant reason was lack of confidence in doctors or diagnostic procedures. Only 6 studies examined attitudes towards antemortem interventions in prospective organ donors. Most respondents supported minimally invasive procedures and only where specific consent was obtained. CONCLUSIONS: Our review suggests a considerable proportion of people, including healthcare professionals, have doubts about the medical and ethical validity of modern determinations of death. The prognosis of brain injury was a more common concern in the context of organ donation decision-making than certainty of death.

Management Considerations for the Surgical Treatment of Colorectal Cancer During the Global Covid-19 Pandemic.

OBJECTIVE: The COVID-19 pandemic requires to conscientiously weigh "timely surgical intervention" for colorectal cancer against efforts to conserve hospital resources and protect patients and health care providers. SUMMARY BACKGROUND DATA: Professional societies provided ad-hoc guidance at the outset of the COVID-19 pandemic on deferral of surgical and perioperative interventions, but these lack specific parameters to determine the optimal timing of surgery. METHODS: Using the GRADE system, published evidence was analyzed to generate weighted statements for stage, site, acuity of presentation, and hospital setting to specify when surgery should be pursued, the time and duration of oncologically acceptable delays, and when to utilize nonsurgical modalities to bridge the waiting period. RESULTS: Colorectal cancer surgeries-prioritized as emergency, urgent with imminent emergency or oncologically urgent, or elective-were matched against the phases of the pandemic. Surgery in COVID-19-positive patients must be avoided. Emergent and imminent emergent cases should mostly proceed unless resources are exhausted. Standard practices allow for postponement of elective cases and deferral to nonsurgical modalities of stage II/III rectal and metastatic colorectal cancer. Oncologically urgent cases may be delayed for 6(-12) weeks without jeopardizing oncological outcomes. Outside established principles, administration of nonsurgical modalities is not justified and increases the vulnerability of patients. CONCLUSIONS: The COVID-19 pandemic has stressed already limited health care resources and forced rationing, triage, and prioritization of care in general, specifically of surgical interventions. Established guidelines allow for modifications of optimal timing and type of surgery for colorectal cancer during an unrelated pandemic.

Multidisciplinary Care for Melanoma of Unknown Primary: Experience in the Era of Molecular Profiling.

BACKGROUND: Melanoma of unknown primary (MUP) accounts for approximately 3% of melanoma diagnoses. This study sought to evaluate treatment and outcomes for a modern MUP cohort. METHODS: A retrospective review of MUP was performed at a tertiary referral cancer center. RESULTS: Of 815 melanoma patients, 67 (8.2%) had MUP. Men were more likely to have MUP than women (67% vs. 55%; p = 0.04). The most common sites of MUP were lymph nodes (28%), visceral solid organs (25%), brain (16%), and skin/subcutaneous tissues (10%). Of the patients who underwent tumor genomic profiling, 52% harbored pathogenic BRAF mutations. Of the 24 patients who underwent multi-gene panel testing, all had pathogenic mutations and 21 (88%) had mutations in addition to or exclusive of BRAF, including 11 patients (46%) with telomerase reverse transcriptase promoter mutations. Checkpoint inhibitors (39%) and BRAF-MEK inhibitors (7%) were the most common first-line treatments. Upfront surgical resection was used for 25% of the MUP patients, and 12 of these resections were for curative intent. During a median follow-up period of 22.1 months, the median overall survival (OS) was not met for the patients with MUP isolated to lymph nodes. At 56.8 months, 75% of these patients were alive. The median OS was 37.4 months for skin/soft tissue MUP, 33.3 months for single solid organ viscera MUP, and 29.8 months for metastatic brain MUP. CONCLUSION: Multigene panel testing identified pathogenic mutations in all tested MUP patients and frequently identified targets outside BRAF. Despite advanced stage, aggressive multimodal therapy for MUP can be associated with 5-year OS and should be pursued for appropriate candidates.

New blood-borne virus infections among organ transplant recipients: An Australian data-linked cohort study examining donor transmissions and other HIV, hepatitis C and hepatitis B notifications, 2000-2015.

BACKGROUND: Blood-borne viral infections can complicate organ transplantation. Systematic monitoring to distinguish donor-transmitted infections from other new infections post transplant is challenging. Administrative health data can be informative. We aimed to quantify post-transplant viral infections, specifically those transmitted by donors and those reactivating or arising new in recipients. METHODS: We linked transplant registries with administrative health data for all solid organ donor-recipient pairs in New South Wales, Australia, 2000-2015. All new recipient notifications of hepatitis B (HBV), C (HCV), or human immunodeficiency virus (HIV) after transplant were identified. Proven/probable donor transmissions within 12 months of transplant were classified using an international algorithm. RESULTS: Of 2120 organ donors, there were 72 with a viral infection (9/72 active, 63/72 past). These 72 donors donated to 173 recipients, of whom 24/173 already had the same infection as their donor, and 149/173 did not, so were at risk of donor transmission. Among those at risk, 3/149 recipients had proven/probable viral transmissions (1 HCV, 2 HBV); none were unrecognized by donation services. There were no deaths from transmissions. There were no donor transmissions from donors without known blood-borne viruses. An additional 68 recipients had new virus notifications, of whom 2/68 died, due to HBV infection. CONCLUSION: This work confirms the safety of organ donation in an Australian cohort, with no unrecognized viral transmissions and most donors with viral infections not transmitting the virus. This may support targeted increases in donation from donors with viral infections. However, other new virus notifications post transplant were substantial and are preventable. Data linkage can enhance current biovigilance systems.

Complete Genome Sequence Resource of a Strain of Curtobacterium flaccumfaciens pv. flaccumfaciens, the Causal Agent of Bacterial Wilt of Common Bean, from Turkey.

Curtobacterium flaccumfaciens pv. flaccumfaciens is the causal agent of bacterial wilt of common bean (Phaseolus vulgaris), a disease that can reduce yields of this economically important crop worldwide. Current genomics resources for this bacterial pathogen are limited. Therefore, long-read sequencing was used to determine the complete genome sequence of a pathogenic C. flaccumfaciens pv. flaccumfaciens strain isolated from common bean leaves showing irregular necrotic lesions with yellow borders collected in a commercial field in Turkey in 2015.

Complete Genome Sequence Data of Three Xylella fastidiosa subsp. multiplex Strains Isolated from Olive Trees in California, U.S.A.

Xylella fastidiosa is a xylem-limited bacterial plant pathogen that causes disease on numerous hosts. Additionally, X. fastidiosa asymptomatically colonizes a wide range of plant species. X. fastidiosa subsp. multiplex has been detected in olive (Olea europaea) trees grown in California, U.S.A., as well as in Europe. Strains of X. fastidiosa subsp. multiplex isolated from California olive trees are not known to cause disease on olive, although some can induce leaf-scorch symptoms on almond (Prunus dulcis). No genome assemblies currently exist for olive-associated X. fastidiosa subsp. multiplex strains; therefore, a hybrid assembly method was used to generate complete genome sequences for three X. fastidiosa subsp. multiplex strains (Fillmore, LM10, and RH1) isolated from olive trees grown in Ventura and Los Angeles counties of California.

Comparative Genomics to Develop a Specific Multiplex PCR Assay for Detection of Clavibacter michiganensis.

Clavibacter michiganensis is a Gram-positive bacterial pathogen that proliferates in the xylem vessels of tomato, causing bacterial wilt and canker symptoms. Accurate detection is a crucial step in confirming outbreaks of bacterial canker and developing management strategies. A major problem with existing detection methods are false-positive and -negative results. Here, we report the use of comparative genomics of 37 diverse Clavibacter strains, including 21 strains sequenced in this study, to identify specific sequences that are C. michiganensis detection targets. Genome-wide phylogenic analyses revealed additional diversity within the genus Clavibacter. Pathogenic C. michiganensis strains varied in plasmid composition, highlighting the need for detection methods based on chromosomal targets. We utilized sequences of C. michiganensis-specific loci to develop a multiplex PCR-based diagnostic platform using two C. michiganensis chromosomal genes (rhuM and tomA) and an internal control amplifying both bacterial and plant DNA (16s ribosomal RNA). The multiplex PCR assay specifically detected C. michiganensis strains from a panel of 110 additional bacteria, including other Clavibacter spp. and bacterial pathogens of tomato. The assay was adapted to detect the presence of C. michiganensis in seed and tomato plant materials with high sensitivity and specificity. In conclusion, the described method represents a robust, specific tool for detection of C. michiganensis in tomato seed and infected plants.

Death, dying and donation: community perceptions of brain death and their relationship to decisions regarding withdrawal of vital organ support and organ donation.

Despite brain death (BD) being established as a definition of death for over 50 years, the concept remains controversial. Little is known about public perception of death determination in decision-making about withdrawal of organ support and organ donation (OD), and the importance of the 'Dead Donor Rule' (DDR). We examined perceptions about death in a BD patient and their relationship to decisions about withdrawal of vital organ support, OD and the DDR, using an online survey of 1017 Australian adults. A BD patient scenario was presented, followed by a series of questions. Statistically significant differences in responses were determined using repeated measures analyses of variance and t tests. Seven hundred and fourteen respondents (70.2%) agreed that a hypothetical BD patient was dead. Those disagreeing most commonly cited the presence of heartbeat and breathing. Seven hundred and seventy (75.7%) favoured removal of 'life support', including 136 (13.3%) who had not agreed the patient was dead. Support for OD was high, but most favoured organ removal only after heartbeat and breathing had ceased. Where OD was in keeping with the patient's known wishes, 464 (45.6%) agreed that organs could be removed even if this caused death. Forty-one (20%) of those who had indicated they considered the patient was not dead agreed to organ removal even if it caused death. Australian public views on BD, withdrawal of 'life support' and OD are complex. Emphasis on prognosis and the impact of significant brain injury may be more appropriate in these situations, rather than focussing on death determination and upholding the DDR.