Publications

BACKGROUND

Squamous cell carcinoma (SCC) is an uncommon histologic subtype of bladder cancer with limited data on treatment patterns, outcomes, and prognostic factors. "Real world" information might inform decision-making, prognostic estimates, and clinical trial designs.

PATIENTS AND METHODS

A retrospective review of patients with tissue-confirmed bladder SCC treated at Cleveland Clinic from 2007 to 2016 was performed. Data on patient characteristics, treatment patterns, and clinical follow-up were extracted. Univariate analysis was used to identify predictors of overall survival (OS), recurrence-free survival (RFS) and time to recurrence.

RESULTS

Of 58 identified patients, 42 had complete data available. Median age at diagnosis was 67 years (range, 37-90). Hematuria was the most common (71%) presenting symptom; 32 patients had pure SCC and 10 predominant/extensive squamous differentiation without major differences noted in clinicopathologic variables or outcomes among those 2 groups. Overall, 35 patients underwent cystectomy with 5 receiving neoadjuvant and 1 adjuvant chemotherapy, whereas 3 had chemotherapy for recurrent disease. Of patients with cystectomy, most had locally advanced disease (75% pT3/4, 35% pN+). Overall, 10 patients progressed and 14 died; median OS was not reached. The 2-year estimated OS, RFS, and cumulative incidence of recurrence were 61% ± 9%, 50% ± 9%, and 32% ± 9%, respectively. Hydronephrosis, older age (70 years or older), lymphovascular invasion, nodal metastases, and advanced T stage were associated with 1 or more poor outcomes.

CONCLUSION

In patients with resectable bladder SCC, radical cystectomy remains the main treatment modality. The role of perioperative chemotherapy remains unclear. The identified prognostic factors might be helpful for prognostication, treatment discussion, and trial eligibility/stratification.

Latent replication-competent HIV-1 persists in individuals on long-term antiretroviral therapy (ART). We developed the Full-Length Individual Proviral Sequencing (FLIPS) assay to determine the distribution of latent replication-competent HIV-1 within memory CD4 T cell subsets in six individuals on long-term ART. FLIPS is an efficient, high-throughput assay that amplifies and sequences near full-length (∼9 kb) HIV-1 proviral genomes and determines potential replication competency through genetic characterization. FLIPS provides a genome-scale perspective that addresses the limitations of other methods that also genetically characterize the latent reservoir. Using FLIPS, we identified 5% of proviruses as intact and potentially replication competent. Intact proviruses were unequally distributed between T cell subsets, with effector memory cells containing the largest proportion of genetically intact HIV-1 proviruses. We identified multiple identical intact proviruses, suggesting a role for cellular proliferation in the maintenance of the latent HIV-1 reservoir.

CONTEXT

Studies on multiple dimensions of the symptom experience of patients with gastrointestinal cancers are extremely limited.

OBJECTIVE

Purpose was to evaluate for changes over time in the occurrence, severity, and distress of seven common symptoms in these patients.

METHODS

Patients completed Memorial Symptom Assessment Scale, six times over two cycles of chemotherapy (CTX). Changes over time in occurrence, severity, and distress of pain, lack of energy, nausea, feeling drowsy, difficulty sleeping, and change in the way food tastes were evaluated using multilevel regression analyses. In the conditional models, effects of treatment group (i.e., with or without targeted therapy), age, number of metastatic sites, time from cancer diagnosis, number of prior cancer treatments, cancer diagnosis, and CTX regimen on enrollment levels, as well as the trajectories of symptom occurrence, severity, and distress were evaluated.

RESULTS

Although the occurrence rates for pain, lack of energy, feeling drowsy, difficulty sleeping, and change in the way food tastes declined over the two cycles of CTX, nausea and numbness/tingling in hands/feet had more complex patterns of occurrence. Severity and distress ratings for the seven symptoms varied across the two cycles of CTX.

CONCLUSIONS

Demographic and clinical characteristics associated with differences in enrollment levels as well as changes over time in occurrence, severity, and distress of these seven common symptoms were highly variable. These findings can be used to identify patients who are at higher risk for more severe and distressing symptoms during CTX and to enable the initiation of preemptive symptom management interventions.

BACKGROUND

Surgical quality datasets can be better tailored toward older adults. The American College of Surgeons (ACS) NSQIP Geriatric Surgery Pilot collected risk factors and outcomes in 4 geriatric-specific domains: cognition, decision-making, function, and mobility. This study evaluated the contributions of geriatric-specific factors to risk adjustment in modeling 30-day outcomes and geriatric-specific outcomes (postoperative delirium, new mobility aid use, functional decline, and pressure ulcers).

STUDY DESIGN

Using ACS NSQIP Geriatric Surgery Pilot data (January 2014 to December 2016), 7 geriatric-specific risk factors were evaluated for selection in 14 logistic models (morbidities/mortality) in general-vascular and orthopaedic surgery subgroups. Hierarchical models evaluated 4 geriatric-specific outcomes, adjusting for hospitals-level effects and including Bayesian-type shrinkage, to estimate hospital performance.

RESULTS

There were 36,399 older adults who underwent operations at 31 hospitals in the ACS NSQIP Geriatric Surgery Pilot. Geriatric-specific risk factors were selected in 10 of 14 models in both general-vascular and orthopaedic surgery subgroups. After risk adjustment, surrogate consent (odds ratio [OR] 1.5; 95% CI 1.3 to 1.8) and use of a mobility aid (OR 1.3; 95% CI 1.1 to 1.4) increased the risk for serious morbidity or mortality in the general-vascular cohort. Geriatric-specific factors were selected in all 4 geriatric-specific outcomes models. Rates of geriatric-specific outcomes were: postoperative delirium in 12.1% (n = 3,650), functional decline in 42.9% (n = 13,000), new mobility aid in 29.7% (n = 9,257), and new or worsened pressure ulcers in 1.7% (n = 527).

CONCLUSIONS

Geriatric-specific risk factors are important for patient-centered care and contribute to risk adjustment in modeling traditional and geriatric-specific outcomes. To provide optimal patient care for older adults, surgical datasets should collect measures that address cognition, decision-making, mobility, and function.

BACKGROUND

Multidrug-resistant tuberculosis (MDR-TB) is an important global public health threat, but accurate estimates of MDR-TB burden among children are lacking.

METHODS

We analyzed demographic, clinical, and laboratory data for newly diagnosed pediatric (age <15 years) TB cases reported to the US National TB Surveillance System during 1993-2014. MDR-TB was defined as culture-confirmed TB disease with resistance to at least isoniazid and rifampicin. To ascertain potential underestimation of pediatric MDR-TB, we surveyed high-burden states for clinically diagnosed cases treated for MDR-TB.

RESULTS

Of 20789 pediatric TB cases, 5162 (24.8%) had bacteriologically confirmed TB. Among 4826 (93.5%) with drug susceptibility testing, 82 (1.7%) had MDR-TB. Most pediatric MDR-TB cases were female (n = 51 [62%]), median age was 5 years (interquartile range, 1-12 years), one-third were Hispanic (n = 28 [34%]), and two-thirds (n = 55 [67%]) were born in the United States. Most cases had additional resistance to ≥1 other first-line drug (n = 66 [81%]) and one-third had resistance to ≥1 second-line drug (24/73 tested). Of 77 who started treatment prior to 2013, 66 (86%) completed treatment and 4 (5%) died. Among the 4 high-TB-burden states/jurisdictions surveyed, there was 42%-55% underestimation of pediatric MDR-TB cases when using only culture-confirmed case definitions.

CONCLUSIONS

Only one-quarter of pediatric TB cases had culture-confirmed TB, likely resulting in underestimation of true pediatric MDR-TB burden in the United States using strictly bacteriologic criteria. Better estimates of pediatric MDR-TB burden in the United States are needed and should include clinical diagnoses based on epidemiologic criteria.

BACKGROUND

Errant neovascularization and coronary artery fistulae (CAF) are frequently observed after cardiac transplantation. The relationship between angiographic neovascularization/CAF and coronary plaque progression is unknown.

METHODS

Angiography and intravascular ultrasound were routinely performed at 4-6 weeks and 1-year post-transplant. Pts were divided into three groups: no angiographic angiogenesis (Group 1), neovascularization only (Group 2), and CAF (Group 3). First-year changes in maximal intimal thickness (MIT), maximal intimal area (MIA), and percent atheroma volume (PAV) were compared between groups.

RESULTS

The 106 pts were included, 40/106 in Group 1, 42/106 in Group 2, and 24/106 in Group 3. Respectively, first-year ΔMIT was 0.14 ± 0.13 mm, 0.32 ± 0.26 mm, and 0.50 ± 0.34 mm, P < .001. ΔMIA was 0.6 ± 0.6 mm , 1.7 ± 1.8 mm , and 3.0 ± 2.6 mm , P < .001. ΔPAV was 2.3 ± 2.5%, 6.0 ± 5.1%, and 9.6 ± 9.0%, P < .001. Rapid plaque progression occurred in 1/40 (2.5%) pts in Group 1, 12/42 (28.6%) in Group 2, and 12/24 (50%) in Group 3, P < .001. Multivariate analysis identified both antithymocyte globulin and presence of CAF as independently associated with rapid plaque progression: OR 0.29 (P = .038) and 4.04 (P = .014).

CONCLUSION

Neovascularization and CAF are commonly present on surveillance angiography after cardiac transplantation and may signify amplified angiogenesis. Their presence is associated with accelerated coronary plaque progression by IVUS.