Real-World Outcomes of Latinx Versus Non-Latinx Patients Treated With First-Line Immunotherapy for Metastatic Renal-Cell Carcinoma.

BACKGROUND: There are limited data regarding the impact of ethnicity among patients receiving immune checkpoint inhibitors. We evaluated real-world outcomes between Latinx and non-Latinx patients with metastatic renal-cell carcinoma (mRCC) treated with first-line nivolumab/ipilimumab within 2 different healthcare settings. METHODS: We performed a retrospective analysis of patients with mRCC who received nivolumab/ipilimumab within the Los Angeles County Department of Health Services (LAC-DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between January 1, 2015 and December 31, 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and covariates were adjusted using multivariate Cox proportional hazards regression. RESULTS: Of 94 patients, 40 patients (43%) were Latinx while the remainder were non-Latinx (44 pts [46%] White, 7 pts [7%] Asian, and 3 pts [3%] Other). Fifty (53%) and 44 (47%) patients received their care at COH and LAC-DHS, respectively. Most Latinx patients (95%) were treated at LAC-DHS, and most non-Latinx patients (89%) were treated at COH. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs. 25.2 months, hazard ratios [HR] 3.61, 95% CI 1.96-6.66, P ≤ .01). Multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; P = .01). At a median follow-up of 11.0 months, the median OS was not reached in either arm at the time of data cutoff. CONCLUSION: Latinx patients with mRCC had a shorter PFS treated with frontline nivolumab/ipilimumab compared to their non-Latinx counterparts. No difference was observed in OS although these data were immature. Larger studies are needed to further interrogate the social and economic determinants of ethnicity on clinical outcomes in mRCC.

Acute vision loss due to CML leukemic retinopathy reversed with leukapheresis.

Leukemic retinopathy is a severe complication of severe leukocytosis that results from untreated chronic myelogenous leukemia (CML). Immediate cytoreduction via leukapheresis may reverse ocular manifestations and prevent permanent vision damage. We present a case of a patient with acute unilateral vision loss found to have leukemic retinopathy in the setting of untreated CML with improvement of visual symptoms after leukapheresis and initiation of hydroxyurea.

Applying Lean Kaizen to Improve Timely Computed Tomography Scan Appointments for Oncology Patients in a Safety Net Hospital.

PURPOSE: Timely radiographic studies are essential to oncology care. At our institution, a safety net hospital in a large metropolitan area, baseline assessment determined that the overwhelming majority of outpatient computed tomographic (CT) scans for oncology patients were overdue and not scheduled within 2 weeks of their first requested date. METHODS: We conducted a series of structured, interdisciplinary meetings including staff from radiology, oncology, scheduling, and administration to critically review the scheduling process utilizing Lean Kaizen quality improvement methods. A new workflow was developed in which clinic staff scheduled CT scans before clinic discharge. Three months after our initial meeting, the new workflow was launched. We set a target of decreasing the percentage of overdue scans to below 20%. RESULTS: At baseline, 87% (65 of 75) of CT scans awaiting scheduling were overdue. Data were gathered at 5 and 10 weeks after implementation of our workflow. The percentage of CT scans overdue for scheduling was 17% (9 of 53) at 5 weeks and 0.97% (1 of 103) at 10 weeks after implementation. Clinic visit durations were not affected. CONCLUSION: The Lean Kaizen QI model was successful in decreasing the rate of oncology patients overdue for CT scan scheduling with minimal effects on clinic visit durations. This study demonstrated the importance of interdepartmental collaboration and continuous monitoring for improvement. Given the success of this project, this workflow will be expanded to other outpatient clinics within our institution.

Superior Mesenteric Vein Thrombosis in the Setting of Ileitis: Case Report and Literature Review.

Acute mesenteric vein thrombosis represents a rare but potentially lethal thrombotic event. Its treatment involves prompt and aggressive anticoagulation therapy. In the perioperative setting, management of the underlying thrombus must be weighed carefully against the risk of bleeding. We describe a 57-year-old man who presented with abdominal pain and was found to have terminal ileitis with concomitant superior mesenteric vein thrombosis.

HIV-2 Drug Resistance Genotyping from Dried Blood Spots.

The treatment of HIV-2 in resource-limited settings (RLS) is complicated by the limited availability of HIV-2-active antiretroviral drugs and inadequate access to HIV-2 viral load and drug resistance testing. Dried blood spots (DBS)-based drug resistance testing, widely studied for HIV-1, has not been reported for HIV-2 and could present an opportunity to improve care for HIV-2-infected individuals. We selected 150 DBS specimens from ongoing studies of antiretroviral therapy (ART) for HIV-2 infection in Senegal and subjected them to genotypic drug resistance testing. Total nucleic acid was extracted from DBS, reverse transcribed, PCR amplified, and analyzed by population-based Sanger sequencing, and major drug resistance-associated mutations (RAM) were identified. Parallel samples from plasma and peripheral blood mononuclear cells (PBMC) were also genotyped. We obtained 58 protease/reverse transcriptase genotypes. Plasma viral load was significantly correlated with genotyping success (P < 0.001); DBS samples with corresponding plasma viral load >250 copies/ml had a success rate of 86.8%. In paired DBS-plasma genotypes, 83.8% of RAM found in plasma were also found in DBS, and replicate DBS genotyping revealed that a single test detected 86.7% of known RAM. These findings demonstrate that DBS-based genotypic drug resistance testing for HIV-2 is feasible and can be deployed in RLS with limited infrastructure.

The Red Reflex Exam: Highlighting the Importance of Physical Exam Maneuvers.

A pediatric well-child physical examination consists of various assessments that screen for common abnormalities during development. Checking the red reflex is one such assessment, with the absence of a red reflex indicating a potential ocular abnormality such as a retinoschisis. Both the American Academy of Pediatrics and the American Academy of Family Physicians have guidelines that call for routine screening of the red reflex from infancy through adolescence. This exam has a high specificity if performed correctly, underlining the utility of this test. This case details a pediatric patient diagnosed with retinoschisis following an absent red reflex noted by a primary care physician. We illustrate the importance of routine exam maneuvers like the red light reflex in routine physical examinations for the screening and diagnosis of illnesses that can significantly alter a child's quality of life over time.

The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1.

Treatment options for individuals infected with human immunodeficiency virus type 2 (HIV-2) are restricted by the intrinsic resistance of the virus to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and the reduced susceptibility of HIV-2 to several protease inhibitors (PIs) used in antiretroviral therapy (ART). In an effort to identify new antiretrovirals for HIV-2 treatment, we evaluated the in vitro activity of the investigational nucleoside analog BMS-986001 (2',3'-didehydro-3'-deoxy-4'-ethynylthymidine; also known as censavudine, festinavir, OBP-601, 4'-ethynyl stavudine, or 4'-ethynyl-d4T). In single-cycle assays, BMS-986001 inhibited HIV-2 isolates from treatment-naive individuals, with 50% effective concentrations (EC50s) ranging from 30 to 81 nM. In contrast, EC50s for group M and O isolates of HIV-1 ranged from 450 to 890 nM. Across all isolates tested, the average EC50 for HIV-2 was 9.5-fold lower than that for HIV-1 (64 ± 18 nM versus 610 ± 200 nM, respectively; mean ± standard deviation). BMS-986001 also exhibited full activity against HIV-2 variants whose genomes encoded the single amino acid changes K65R and Q151M in reverse transcriptase, whereas the M184V mutant was 15-fold more resistant to the drug than the parental HIV-2ROD9 strain. Taken together, our findings show that BMS-986001 is an effective inhibitor of HIV-2 replication. To our knowledge, BMS-986001 is the first nucleoside analog that, when tested against a diverse collection of HIV-1 and HIV-2 isolates, exhibits more potent activity against HIV-2 than against HIV-1 in culture.

Validation of rice genome sequence by optical mapping.

BACKGROUND: Rice feeds much of the world, and possesses the simplest genome analyzed to date within the grass family, making it an economically relevant model system for other cereal crops. Although the rice genome is sequenced, validation and gap closing efforts require purely independent means for accurate finishing of sequence build data. RESULTS: To facilitate ongoing sequencing finishing and validation efforts, we have constructed a whole-genome SwaI optical restriction map of the rice genome. The physical map consists of 14 contigs, covering 12 chromosomes, with a total genome size of 382.17 Mb; this value is about 11% smaller than original estimates. 9 of the 14 optical map contigs are without gaps, covering chromosomes 1, 2, 3, 4, 5, 7, 8 10, and 12 in their entirety - including centromeres and telomeres. Alignments between optical and in silico restriction maps constructed from IRGSP (International Rice Genome Sequencing Project) and TIGR (The Institute for Genomic Research) genome sequence sources are comprehensive and informative, evidenced by map coverage across virtually all published gaps, discovery of new ones, and characterization of sequence misassemblies; all totalling ~14 Mb. Furthermore, since optical maps are ordered restriction maps, identified discordances are pinpointed on a reliable physical scaffold providing an independent resource for closure of gaps and rectification of misassemblies. CONCLUSION: Analysis of sequence and optical mapping data effectively validates genome sequence assemblies constructed from large, repeat-rich genomes. Given this conclusion we envision new applications of such single molecule analysis that will merge advantages offered by high-resolution optical maps with inexpensive, but short sequence reads generated by emerging sequencing platforms. Lastly, map construction techniques presented here points the way to new types of comparative genome analysis that would focus on discernment of structural differences revealed by optical maps constructed from a broad range of rice subspecies and varieties.

Evolution of an avirulence gene, AVR1-CO39, concomitant with the evolution and differentiation of Magnaporthe oryzae.

The significance of AVR1-CO39, an avirulence gene of the blast fungus corresponding to Pi-CO39(t) in rice cultivars, during the evolution and differentiation of the blast fungus was evaluated by studying its function and distribution in Pyricularia spp. When the presence or absence of AVR1-CO39 was plotted on a dendrogram constructed from ribosomal DNA sequences, a perfect parallelism was observed between its distribution and the phylogeny of Pyricularia isolates. AVR1-CO39 homologs were exclusively present in one species, Pyricularia oryzae, suggesting that AVR1-CO39 appeared during the early stage of evolution of P. oryzae. Transformation assays showed that all the cloned homologs tested are functional as an avirulence gene, indicating that selection has maintained their function. Nevertheless, Oryza isolates (isolates virulent on Oryza spp.) in P. oryzae were exceptionally noncarriers of AVR1-CO39. All Oryza isolates suffered from one of the two types of known rearrangements at the Avr1-CO39 locus (i.e., G type and J type). These types were congruous to the two major lineages of Oryza isolates from Japan determined by MGR586 and MAGGY. These results indicate that AVR1-CO39 was lost during the early stage of evolution of the Oryza-specific subgroup of P. oryzae. Interestingly, its corresponding resistance gene, Pi-CO39(t), is not widely distributed in Oryza spp.

Analysis of the structure of the AVR1-CO39 avirulence locus in virulent rice-infecting isolates of Magnaporthe grisea.

The AVR1-CO39 gene that came from a Magnaporthe grisea isolate from weeping lovegrass controls avirulence on the rice cultivar CO39. AVR1-CO39 was not present in the genome of the rice-infecting M. grisea isolate Guyll from French Guyana, suggesting that the gene had been deleted. Molecular analysis of the deletion breakpoints in the AVR1-CO39 locus revealed the presence of a truncated copy of a previously unknown retrotransposon at the left-hand border. At the right-hand border was a truncated copy of another repetitive element that is present at multiple locations in the genome of Guyll. The structures of avr1-CO39 loci were further examined in 45 rice-infecting isolates collected in Brazil, China, Japan, India, Indonesia, Mali, and the Philippines. Most isolates showed no hybridization signal with the AVR1-CO39 probe and had the same locus structure as Guyll. Some isolates from Japan showed a signal with the AVR1-CO39 probe, but the region specifying avirulence activity was rearranged. These findings suggest that widespread virulence to 'CO39' among rice-infecting M. grisea isolates is due to ancestral rearrangements at the AVR1-CO39 locus that may have occurred early in the evolution of pathogenicity to rice.