Survival Outcomes of Very Small Drug-Eluting Beads Used in Chemoembolization of Unresectable Hepatocellular Carcinoma.

PURPOSE: To assess the safety and efficacy of transarterial chemoembolization using a 75-µm drug-eluting embolic (DEE) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The medical records of 109 patients with a mean age of 64.1 years (range 85-49) treated for unresectable HCC between November 2013 and August 2016 with transarterial chemoembolization using a 75-µm DEE were retrospectively reviewed. Patients who had prior therapy for HCC were excluded. Child-Pugh A patients and Barcelona Clinic Liver Cancer stages A/B patients constituted 68.8% and 65.1% of the patients, respectively. The mean size of the index tumors was 5.8 cm (range 18.5-1.2) with 42 (39%) patients with central tumors around the porta-hepatis region. Portal vein invasion was seen in 10 (9.2%) patients. Tumor response was categorized according to the modified Response Evaluation Criteria in Solid Tumors 1.1, and the toxicity profile was assessed using Common Terminology Criteria for Adverse Events, version 4.03. RESULTS: At 1-month follow-up, complete response, objective response, and disease control was seen in 23%, 66%, and 90%, respectively. The median progression-free survival was 11.2 months. The median overall survival was 25.1 months (33.4 months for Child-Pugh A and 28.2 months for Barcelona Clinic Liver Cancer stages A/B), and transplant-free survival was 21.3 months. The 6-, 12-, and 24-month survivals were 91.7%, 75.5%, and 50.5%, respectively. Grade 3 toxicity was seen in 1.8% of the patients; no grade 4 or 5 toxicity was reported. CONCLUSIONS: Transarterial chemoembolization using 75-µm DEE is safe and efficacious in the treatment of HCC.

Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting.

The spectrum of somatic alterations in hematologic malignancies includes substitutions, insertions/deletions (indels), copy number alterations (CNAs), and a wide range of gene fusions; no current clinically available single assay captures the different types of alterations. We developed a novel next-generation sequencing-based assay to identify all classes of genomic alterations using archived formalin-fixed paraffin-embedded blood and bone marrow samples with high accuracy in a clinically relevant time frame, which is performed in our Clinical Laboratory Improvement Amendments-certified College of American Pathologists-accredited laboratory. Targeted capture of DNA/RNA and next-generation sequencing reliably identifies substitutions, indels, CNAs, and gene fusions, with similar accuracy to lower-throughput assays that focus on specific genes and types of genomic alterations. Profiling of 3696 samples identified recurrent somatic alterations that impact diagnosis, prognosis, and therapy selection. This comprehensive genomic profiling approach has proved effective in detecting all types of genomic alterations, including fusion transcripts, which increases the ability to identify clinically relevant genomic alterations with therapeutic relevance.

Accessibility and Content of Abdominal Transplant Fellowship Program Websites in the United States.

OBJECTIVES: Organ transplant volume is at an all-time high. Prospective applicants often utilize individual programs' websites for information when deciding if and where to apply for fellowship training. Accessibility and content from one program's website to the next is highly variable and may contribute to the selection of programs. The aim of this study was to evaluate the accessibility and content of abdominal transplant surgery fellowship websites. MATERIALS AND METHODS: The American Society of Transplant Surgeons (ASTS) website provides a complete list of abdominal transplant fellowship programs in the United States. A Google search was performed to determine the presence and accessibility of a program's website. Available websites were evaluated on the presence of 20 content criteria. RESULTS: Sixty-five programs in the United States were identified using the ASTS directory. Websites for fifty-one (78%) fellowship programs were identified. Three-fourths of websites contained 50% or less of the 20 evaluated data points, whereas 24% of websites contained 5 or less criteria. The most and least included data points were program description (100%) and on-call expectations (10%), respectively. CONCLUSIONS: The accessibility and content of a program's website is one major factor that can influence a potential applicant's decision on where to pursue transplant surgery fellowship training. This study revealed that a significant percentage of programs fail to provide a functional website. Of the fifty-one programs that did have websites, information deemed important to prospective applicants may be considered inadequate.

A SEER Database Analysis of the Survival Advantage of Transarterial Chemoembolization for Hepatocellular Carcinoma: An Underutilized Therapy.

PURPOSE: To measure transarterial chemoembolization utilization and survival benefit among patients with hepatocellular carcinoma (HCC) in the Surveillance, Epidemiology, and End Results (SEER) patient population. MATERIALS AND METHODS: A retrospective study identified 37,832 patients with HCC diagnosed between 1991 and 2011. Survival was estimated by Kaplan-Meier method and compared by log-rank test. Propensity-score matching was used to address an imbalance of covariates. RESULTS: More than 75% of patients with HCC did not receive any HCC-directed treatment. Transarterial chemoembolization was the most common initial therapy (15.9%). Factors associated with the use of chemoembolization included younger age, more HCC risk factors, more comorbidities, higher socioeconomic status, intrahepatic tumor, unifocal tumor, vascular invasion, and smaller tumor size (all P < .001). Median survival was improved in patients treated with chemoembolization compared with those not treated with chemoembolization (20.1 vs 4.3 mo; P < .0001). Similar findings were demonstrated in propensity-scoring analysis (14.5 vs 4.2 mo; P < .0001) and immortal time bias sensitivity analysis (9.5 vs 3.6 mo; P < .0001). There was a significantly improved survival hazard ratio (HR) in patients treated with chemoembolization (HR, 0.42; 95% confidence interval, 0.39-0.45). CONCLUSIONS: Patients with HCC treated with transarterial chemoembolization experienced a significant survival advantage compared with those not treated with transarterial chemoembolization. More than 75% of SEER/Medicare patients diagnosed with HCC received no identifiable oncologic treatment. There is a significant public health need to increase awareness of efficacious HCC treatments such as transarterial chemoembolization.

Defining the sham environment for post-myocardial infarction studies in mice.

The purpose of this study was to evaluate the effect of sham surgery in a minimally invasive surgical model of permanent coronary artery occlusion used to generate myocardial infarction (MI) in mice. Adult male C57BL/6J mice (3-6 mo old) were divided into five groups: day (D) 0 (no surgical operation), D1 Sham, D1 MI, D7 Sham, and D7 MI. A refined MI surgery technique was used to approach the coronary artery without the ribs being cut. Both sham and MI mice had the left ventricle (LV) exposed through a small incision. To test the effects of surgery alone, the suture was passed around the coronary artery but not ligated. The MI mice were subjected to permanent coronary artery ligation. The mice were killed at D1 or D7 postsurgical procedure. Compared with D0 no surgery controls, the D1 and D7 sham groups exhibited no surgical mortality and similar necropsy and echocardiographic variables. Surgery alone did not induce an inflammatory cell response, as evidenced by the lack of leukocyte infiltration in the sham groups. Analysis of 165 inflammatory cytokines and extracellular matrix factors in sham revealed that a minor gene response was initiated but not translated to protein levels. Collagen deposition did not occur in the absence of MI. In contrast, the D1 and D7 MI groups showed the expected robust inflammatory and scar formation responses. When a minimally invasive procedure to generate MI in mice was used, the D0 (no surgical operation) control was an adequate replacement for the use of sham surgery groups.

Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non-resectable hepatocellular carcinoma tumours of ≥ 3 cm.

OBJECTIVES: The optimal locoregional treatment for non-resectable hepatocellular carcinoma (HCC) of ≥ 3 cm in diameter is unclear. Transarterial chemoembolization (TACE) is the initial intervention most commonly performed, but it rarely eradicates HCC. The purpose of this study was to measure survival in HCC patients treated with adjuvant stereotactic body radiotherapy (SBRT) following TACE. METHODS: A retrospective study of patients with HCC of ≥ 3 cm was conducted. Outcomes in patients treated with TACE alone (n = 124) were compared with outcomes in those treated with TACE + SBRT (n = 37). RESULTS: There were no significant baseline differences between the two groups. The pre-TACE mean number of tumours (P = 0.57), largest tumour size (P = 0.09) and total tumour diameter (P = 0.21) did not differ significantly between the groups. Necrosis of the HCC tumour, measured after the first TACE, did not differ between the groups (P = 0.69). Local recurrence was significantly decreased in the TACE + SBRT group (10.8%) in comparison with the TACE-only group (25.8%) (P = 0.04). After censoring for liver transplantation, overall survival was found to be significantly increased in the TACE + SBRT group compared with the TACE-only group (33 months and 20 months, respectively; P = 0.02). CONCLUSIONS: This retrospective study suggests that in patients with HCC tumours of ≥ 3 cm, treatment with TACE + SBRT provides a survival advantage over treatment with only TACE. Confirmation of this observation requires that the concept be tested in a prospective, randomized clinical trial.

Predictors of repeat transarterial chemoembolization in the treatment of hepatocellular carcinoma.

OBJECTIVES: Repeat transarterial chemoembolization (TACE) is a common intervention performed for hepatocellular carcinoma (HCC). The aim of this study was to identify predictors of the need for repeat TACE. METHODS: Between 2008 and 2012, data on patient and tumour variables were collected for 262 patients treated with a first TACE procedure for HCC. The decision to perform repeat TACE procedures was made at the completion of the first TACE or after follow-up imaging demonstrated the subtotal treatment of HCC tumours. RESULTS: Repeat TACE was performed in 67 of 262 (25.6%) patients. Necrosis of HCC, measured after the first TACE, was lower in patients who subsequently received repeat TACE (P = 0.042). On multivariable analysis, total tumour diameter of >5 cm [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.45-5.25; P = 0.002] and increasing age (OR 1.04/year, 95% CI 1.00-1.07; P = 0.030) were predictive of the need for repeat TACE. Measures of liver function and TACE approach (selective versus non-selective) were not predictive of repeat TACE. Median survival did not differ significantly between patients who did (median survival: 21.1 months) and did not (median survival: 26.1 months) receive a repeat TACE procedure (P = 0.574). CONCLUSIONS: The requirement for repeat TACE is associated with older age, increased HCC tumour burden and subtotal TACE-induced HCC necrosis. Importantly, repeat TACE was not associated with reduced survival.

Chemoembolization outcomes for hepatocellular carcinoma in cirrhotic patients with compromised liver function.

BACKGROUND: Transarterial chemoembolization (TACE) is recommended as a treatment for unresectable hepatocellular carcinoma (HCC) in patients with normal underlying liver function. The efficacy of TACE in cirrhotic patients with compromised liver function is unknown. METHODS: All 'first' TACE interventions for HCC performed at a single institution from 2008 to 2012 were retrospectively reviewed (n = 190). Liver function was quantified via the Child's score. Tumour necrosis after TACE was quantified via the mRECIST criteria. RESULTS: The 'first' TACE procedures of 100 Child's A and 90 Child's B/C cirrhotic patients were evaluated. As expected, the lab-model for end-stage liver disease (MELD) score was significantly higher in the Child's B/C group. Although the number of tumours were similar between the groups, both the size of the largest tumour and the total tumour diameter were greater in the Child's A group. There were no significant differences in post-TACE tumour necrosis between groups. The median survival after TACE was significantly longer in the Child's A compared with Child's B/C patients (21.9 versus 13.7 months, P = 0.03). CONCLUSIONS: TACE appears to be equally efficacious in cirrhotic patients regardless of their Child's classification based upon equivalent mRECIST measures of tumour necrosis. However, inferior survival after TACE was observed in the Child's B/C group.

Population genomic sequencing of Coccidioides fungi reveals recent hybridization and transposon control.

We have sequenced the genomes of 18 isolates of the closely related human pathogenic fungi Coccidioides immitis and Coccidioides posadasii to more clearly elucidate population genomic structure, bringing the total number of sequenced genomes for each species to 10. Our data confirm earlier microsatellite-based findings that these species are genetically differentiated, but our population genomics approach reveals that hybridization and genetic introgression have recently occurred between the two species. The directionality of introgression is primarily from C. posadasii to C. immitis, and we find more than 800 genes exhibiting strong evidence of introgression in one or more sequenced isolates. We performed PCR-based sequencing of one region exhibiting introgression in 40 C. immitis isolates to confirm and better define the extent of gene flow between the species. We find more coding sequence than expected by chance in the introgressed regions, suggesting that natural selection may play a role in the observed genetic exchange. We find notable heterogeneity in repetitive sequence composition among the sequenced genomes and present the first detailed genome-wide profile of a repeat-induced point mutation (RIP) process distinctly different from what has been observed in Neurospora. We identify promiscuous HLA-I and HLA-II epitopes in both proteomes and discuss the possible implications of introgression and population genomic data for public health and vaccine candidate prioritization. This study highlights the importance of population genomic data for detecting subtle but potentially important phenomena such as introgression.

Career Outcomes of Nondesignated Preliminary Surgery Residents: A Systematic Review and Meta-Analysis.

OBJECTIVE: Nondesignated preliminary surgery (NDPS) residency offers postgraduate medical education with no guarantee of a subsequent categorical position. Some literature exists detailing the career outcomes of these residents, but these results are complicated by the limited scale of these studies. The purpose of this systematic review and meta-analysis is to summarize the career outcomes of these residents from the existing literature. METHODS: The PubMed, Scopus, Cochrane, CINAHL, and PsycINFO databases were queried from inception for studies reporting the career outcomes of NDPS residents. Data were collected and extracted by 2 independent reviewers in accordance with PRISMA guidelines. The primary outcome of this study is the proportion of NDPS residents obtaining a categorical general surgery position. Secondary outcomes include the percentages of residents obtaining surgical subspecialty positions, obtaining nonsurgical specialty positions, and leaving graduate medical education. RESULTS: Overall, 13 studies reporting NDPS residents (n = 2606) were identified. The overall pooled estimate for obtaining a categorical general surgery position after NDPS residency was 37.1% (95% CI, 31.3%-43.2%), with significant heterogeneity (I2 = 81.8%; p < 0.001). Residents in the second postgraduate year were significantly more likely than those in the first year to obtain a general surgery position (50.6% vs 29.0%, respectively; p < 0.001). Residents subsequently training in a surgical subspecialty (13.3%) largely entered orthopedics (3.6%), urology (2.1%), and obstetrics and gynecology (1.6%). For residents entering nonsurgical training (32.1%), a majority entered anesthesiology (11.7%), internal medicine (3.8%), and radiology (3.8%). CONCLUSIONS: Although NDPS residents have heterogenous career outcomes, they largely obtain categorical positions in general surgery and surgical subspecialties.

Successful Surgical Management of an Invasive Adenocarcinoma Within a Duplicated Gallbladder by an Extensive Hepatic Resection: A Case Report.

Identifying a duplicated gallbladder is a rather rare entity, but a well-described phenomenon within the current literature. Although this finding has been described in numerous case reports, management remains poorly defined and the diagnosis is often difficult. We present a case of a patient with a suspected duplicated gallbladder versus a choledochocele that was diagnosed later on with adenocarcinoma within a duplicated gallbladder during surgical management requiring extended hepatic resection for curative intent. This case emphasizes the importance of radiological techniques in diagnosing such rare cases and the surgical approach of managing adenocarcinoma in the presence of this rare anatomical malformation.

General surgery applicant perspectives: Two years of virtual interview experiences and supplemental application impressions.

BACKGROUND: We sought to evaluate the unique benefits and challenges the virtual recruitment and interviewing platform had on general surgery residency applicants. METHODS: Applicants who interviewed for a categorical position at our institution during the 2021 and 2022 Match season were contacted to participate in the anonymous online survey focused on applicant behavior related to the virtual interview format. Data were analyzed using chi-square and paired t-tests. RESULTS: A response rate of 56.7 â€‹% (n â€‹= â€‹135) was achieved. Applicants accepted a median of 17 (IQR 13-20) interviews in 2021 and 15 (IQR 11-19) interviews in 2022. More than half (54 â€‹%) of applicants indicated they applied to more programs, and 53 â€‹% accepted more interviews, because of the virtual format. The greatest advantages of the virtual interviews as cited by applicants were saving money (96.3 â€‹%), saving time (49.6 â€‹%), and avoiding travel risks (43.7 â€‹%). The top limitations of virtual interviews were less exposure to current residents and faculty (61.5 â€‹%), to the city or location of the program (58.5 â€‹%), and difficultly comparing programs (57.8 â€‹%). The 2022 Match cycle included use of the supplemental application; however, 85 â€‹% of applicants did not feel that the supplemental improved their overall application. Some applicants (20 â€‹%) who "signaled" programs did not receive an interview offer from any of the programs they signaled. CONCLUSION: The transition to virtual interviews saved applicants time and money but limited their exposure. Future efforts to maintain virtual interviews will need to be balanced against the intangible benefit of human interaction and observing a program's culture.

Comparative analysis of Mycobacterium and related Actinomycetes yields insight into the evolution of Mycobacterium tuberculosis pathogenesis.

BACKGROUND: The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. RESULTS: Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. CONCLUSIONS: Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org.

Early Assessment of National Kidney Allocation Policy Change.

BACKGROUND: The new kidney allocation changes with elimination of donor service areas (DSAs) and Organ Procurement and Transplantation Network regions were initiated to improve equity in organ allocation. The aim of this evaluation was to determine the operational, financial, and recipient-related effect of the new allocation system on a large rural transplantation program. STUDY DESIGN: A retrospective, cross-sectional analysis of organ offers, allograft outcomes, and attributed costs in a comparative time cohort, before (December 16, 2020 to March 14, 2021) and after (March 15, 2021 to June 13, 2021) the allocation change was performed. Outcomes were limited to adult, solitary, deceased donor kidney transplantations. RESULTS: We received 198,881 organ offers from 3,886 organ donors at our transplantation center from December 16, 2020 to June 31, 2021: 87,643 (1,792 organ donors) before the change and 111,238 (2094 organ donors) after the change, for a difference of +23,595 more offers (+302 organ donors). This resulted in 6.5 more organs transplanted vs a predicted loss of 4.9 per month. Local organ offers dropped from 70% to 23%. There was a statistically significantly increase in donor terminal serum creatinine (1.2 ± 0.86 mg/dL vs 2.2 ± 2.3 mg/dL, p < 0.001), kidney donor profile index (KDPI) (39 ± 20 vs 48 ± 22, p = 0.017), cold ischemia time (16 ± 7 hours vs 21 ± 6 hours, p < 0.001), and delayed graft function rates (23% vs 40%, p = 0.020). CONCLUSION: The new kidney allocation policy has led to an increase in KDPI of donors with longer cold ischemia time, leading to higher delayed graft function rates. This has resulted in increasing logistical and financial burdens on the system. Implementing large-scale changes in allocation based predominantly on predictive modeling needs to be intensely reassessed during a longer follow up.

Clinical and analytical validation of FoundationOne®CDx, a comprehensive genomic profiling assay for solid tumors.

FoundationOne®CDx (F1CDx) is a United States (US) Food and Drug Administration (FDA)-approved companion diagnostic test to identify patients who may benefit from treatment in accordance with the approved therapeutic product labeling for 28 drug therapies. F1CDx utilizes next-generation sequencing (NGS)-based comprehensive genomic profiling (CGP) technology to examine 324 cancer genes in solid tumors. F1CDx reports known and likely pathogenic short variants (SVs), copy number alterations (CNAs), and select rearrangements, as well as complex biomarkers including tumor mutational burden (TMB) and microsatellite instability (MSI), in addition to genomic loss of heterozygosity (gLOH) in ovarian cancer. CGP services can reduce the complexity of biomarker testing, enabling precision medicine to improve treatment decision-making and outcomes for cancer patients, but only if test results are reliable, accurate, and validated clinically and analytically to the highest standard available. The analyses presented herein demonstrate the extensive analytical and clinical validation supporting the F1CDx initial and subsequent FDA approvals to ensure high sensitivity, specificity, and reliability of the data reported. The analytical validation included several in-depth evaluations of F1CDx assay performance including limit of detection (LoD), limit of blank (LoB), precision, and orthogonal concordance for SVs (including base substitutions [SUBs] and insertions/deletions [INDELs]), CNAs (including amplifications and homozygous deletions), genomic rearrangements, and select complex biomarkers. The assay validation of >30,000 test results comprises a considerable and increasing body of evidence that supports the clinical utility of F1CDx to match patients with solid tumors to targeted therapies or immunotherapies based on their tumor's genomic alterations and biomarkers. F1CDx meets the clinical needs of providers and patients to receive guideline-based biomarker testing, helping them keep pace with a rapidly evolving field of medicine.

Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies.

Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella Pathogenicity Island, and acquisition of individual loci, adaptation by gene loss in the more recently emerged tularensis, holarctica, and mediasiatica subspecies occurred and was distinct from evolutionary events that differentiated these subspecies, and the novicida subspecies, from a common ancestor. Our findings are applicable to future studies focused on variations in Francisella subspecies pathogenesis, and of broader interest to studies of genomic pathoadaptation in bacteria.

TB database: an integrated platform for tuberculosis research.

The effective control of tuberculosis (TB) has been thwarted by the need for prolonged, complex and potentially toxic drug regimens, by reliance on an inefficient vaccine and by the absence of biomarkers of clinical status. The promise of the genomics era for TB control is substantial, but has been hindered by the lack of a central repository that collects and integrates genomic and experimental data about this organism in a way that can be readily accessed and analyzed. The Tuberculosis Database (TBDB) is an integrated database providing access to TB genomic data and resources, relevant to the discovery and development of TB drugs, vaccines and biomarkers. The current release of TBDB houses genome sequence data and annotations for 28 different Mycobacterium tuberculosis strains and related bacteria. TBDB stores pre- and post-publication gene-expression data from M. tuberculosis and its close relatives. TBDB currently hosts data for nearly 1500 public tuberculosis microarrays and 260 arrays for Streptomyces. In addition, TBDB provides access to a suite of comparative genomics and microarray analysis software. By bringing together M. tuberculosis genome annotation and gene-expression data with a suite of analysis tools, TBDB (http://www.tbdb.org/) provides a unique discovery platform for TB research.

Dynamics of Pseudomonas aeruginosa genome evolution.

One of the hallmarks of the Gram-negative bacterium Pseudomonas aeruginosa is its ability to thrive in diverse environments that includes humans with a variety of debilitating diseases or immune deficiencies. Here we report the complete sequence and comparative analysis of the genomes of two representative P. aeruginosa strains isolated from cystic fibrosis (CF) patients whose genetic disorder predisposes them to infections by this pathogen. The comparison of the genomes of the two CF strains with those of other P. aeruginosa presents a picture of a mosaic genome, consisting of a conserved core component, interrupted in each strain by combinations of specific blocks of genes. These strain-specific segments of the genome are found in limited chromosomal locations, referred to as regions of genomic plasticity. The ability of P. aeruginosa to shape its genomic composition to favor survival in the widest range of environmental reservoirs, with corresponding enhancement of its metabolic capacity is supported by the identification of a genomic island in one of the sequenced CF isolates, encoding enzymes capable of degrading terpenoids produced by trees. This work suggests that niche adaptation is a major evolutionary force influencing the composition of bacterial genomes. Unlike genome reduction seen in host-adapted bacterial pathogens, the genetic capacity of P. aeruginosa is determined by the ability of individual strains to acquire or discard genomic segments, giving rise to strains with customized genomic repertoires. Consequently, this organism can survive in a wide range of environmental reservoirs that can serve as sources of the infecting organisms.

Double partial nephrectomy in allograft transplanted kidney.

A 61-year-old female presented with an incidental anterior mid pole renal mass on ultrasound. She had previously undergone live directed donor renal transplantation 13 years prior. As the 10 year survival of living transplant recipients increases, malignancy presentations will continue to rise. Nephron sparing surgery in renal allografts is sparse due to difficult operative dissection and complicated hila vascular control. We present the use of manual atraumatic graded bowel clamp pressure around the resected tumour as a viable option to safely perform partial nephrectomy in a transplanted kidney.

Maintaining Equity and Access: Successful Implementation of a Virtual Kidney Transplantation Evaluation.

BACKGROUND: Maintaining access to kidney transplantation during a pandemic is a challenge, particularly for centers that serve a large rural and minority patient population with an additional burden of travel. The aim of this article was to describe our experience with the rollout and use of a virtual pretransplantation evaluation platform to facilitate ongoing transplant waitlisting during the early peak of the COVID-19 pandemic. STUDY DESIGN: This is a retrospective analysis of the process improvement project implemented to continue the evaluation of potential kidney transplantation candidates and ensure waitlist placement during the COVID-19 pandemic. Operational metrics include transplantation volume per month, referral volume per month, pretransplantation patients halted before completing an evaluation per month, evaluations completed per month, and patients waitlisted per month. RESULTS: Between April and September 2020, a total of 1,258 patients completed an evaluation. Two hundred and forty-seven patients were halted during this time period before completing a full evaluation. One hundred and fifty-two patients were presented at selection and 113 were placed on the waitlist. In addition, the number of patients in the active referral phase was able to be reduced by 46%. More evaluations were completed within the virtual platform (n = 930 vs n = 880), yielding similar additions to the waitlist in 2020 (n = 282) vs 2019 (n = 308) despite the COVID-19 pandemic. CONCLUSIONS: The virtual platform allowed continued maintenance of a large kidney transplantation program despite the inability to have in-person visits. The value of this platform will likely transform our approach to the pretransplantation process and provides an additional valuable method to improve patient equity and access to transplantation.