Publications

Efficacy of conventional chemoimmunotherapy is limited in patients with Richter syndrome (RS) with anticipated median overall survival (OS) of less than 10 months. Allogeneic hematopoietic cell transplantation (allo-HCT) is commonly offered as a consolidative treatment option in RS. To our knowledge, there are no randomized controlled studies that have compared allo-HCT against other therapies in RS; available allo-HCT data are limited to small case series from single-institution or registry studies. We performed a systematic review and meta-analysis to assess the totality of evidence regarding the efficacy (or lack thereof) of allo-HCT for RS. We extracted data on post-allograft outcomes related to benefits (overall response rate [ORR], complete remission [CR], OS, and progression-free survival [PFS]). For harms, data were extracted on non-relapse mortality (NRM) and relapse post-allografting. Our search strategy identified 240 studies, but only four studies (n = 72 patients) met our inclusion criteria. Pooled ORR, CR, OS, and PFS rates were 79%, 33%, 49%, and 30%, respectively. Pooled NRM and relapse rates were 24% and 28%, respectively. Results of this systematic review and meta-analysis indicate that allo-HCT yields encouraging OS in RS, thus remaining a reasonable treatment option in fit patients whose disease demonstrates a chemosensitive response to pre-transplant salvage therapies. Novel strategies are certainly needed to reduce the risk of relapse to further improve outcomes in these patients.

INTRODUCTION: Lenalidomide maintenance, commonly prescribed in the postautologous transplantation (AHCT) setting for multiple myeloma (MM), is associated with development of secondary primary malignancies (SPM). Proteasome inhibitor maintenance (PIM) has also been evaluated in MM. We conduct a systematic review/meta-analysis to assess the efficacy of PIM in MM.

METHODS: Performing a comprehensive search of the medical literature using PubMed/Medline and EMBASE on September 11, 2019, we extracted data on clinical outcomes related to benefits (OS, PFS, and depth of hematologic response [DOHR]) and harms (SPM and adverse events). 2144 references were identified; three studies were eligible for inclusion.

RESULTS: A total of 1760 patients were included in the analysis; 507 patients received bortezomib and 395 received ixazomib maintenance. Control arms were either placebo (n = 261) or thalidomide (n = 358). PIM did not improve OS (HR 0.88, 95% CI 0.73-1.05, P = .15) but improved PFS (HR 0.77, 95% CI 0.69-0.86, P ≤ .00001) and DOHR (HR 0.88, 95% CI 0.79-0.98, P = .02) compared with control. There were no significant differences between PIM and control regarding SPM (p = NS) and ≥grade 3 peripheral neuropathy (PN) (p = NS).

CONCLUSIONS: PIM following AHCT in MM improves PFS and DOHR without an increase in development of SPM or severe PN compared with placebo/thalidomide.

OBJECTIVE: Describe rehabilitation needs and factors associated with unmet needs at 5 years post-traumatic brain injury (TBI).

SETTING: Five Veterans Affairs (VA) polytrauma rehabilitation centers (PRCs).

PARTICIPANTS: VA TBI Model Systems participants (N = 283; 96% male, 75%, 57% severe TBI).

DESIGN: Prospective observational cohort.

MAIN MEASURES: Rehabilitation Needs Survey (21-item survey that assesses cognitive, emotional, social, and functional needs); Craig Hospital Inventory of Environmental Factors (25-item survey of potential environmental barriers).

RESULTS: Participants endorsed a mean of 8 (SD: 6.2) ongoing and 3 (SD: 4.7) unmet rehabilitation needs at 5 years post-TBI. Approximately 65% of participants reported at least 1 rehabilitation need that remained unmet. The number and nature of needs differed across TBI severity groups. In unadjusted and adjusted linear regression models, Black race and environmental barriers (Craig Hospital Inventory of Environmental Factors total score) were predictive of unmet needs (P < .001). Those with greater unmet needs reported the physical environment (54%-63%), informational sources (54%), social attitudes (55%), healthcare access (40%), public policy (32%-37%), transportation availability (33%), and in-home assistance (32%) as the most frequent environmental barriers at 5 years post-TBI.

CONCLUSION: Veterans and Service Members continue to have rehabilitation needs at 5 years post-TBI. Veterans Affairs programs to address ongoing needs and policy to support them are needed.

RATIONALE, AIMS, AND OBJECTIVES: Assessing the performance of diagnostic tests requires evaluation of the amount of diagnostic uncertainty a test reduces. Statistical measures, such as sensitivity and specificity, currently dominating the evidence-based medicine (EBM) and related fields, cannot explicitly measure this reduction in diagnostic uncertainty. Mutual information (MI), an information theory statistic, explicitly quantifies diagnostic uncertainty by measuring information gain before vs after diagnostic testing. In this paper, we propose the use of MI as a single measure to express diagnostic test performance and demonstrate how it can be used in the meta-analysis of diagnostic test studies.

METHODS: We use two case studies from the literature to demonstrate the applicability of MI meta-analysis in assessing diagnostic performance. Meta-analysis of studies evaluating (a) ultrasonography (US) to detect endometrial cancer and (b) magnetic resonance angiography to detect arterial stenosis.

RESULTS: The results of MI meta-analyses are comparable to those of traditional statistical measures' meta-analyses. However, the results of MI are easier to understand as it relates directly to the extent of uncertainty a diagnostic test can reduce. For example, the US test, diagnosing endometrial cancer, is 40% specific and 94% sensitive. The combination of these values is difficult to interpret and may lead to inappropriate assessment (eg, one could favour the test due to its high sensitivity, ignoring its low specificity). In terms of MI, however, a single metric shows that the test reduces diagnostic uncertainty by 10%, which many users may consider small under most circumstances.

CONCLUSIONS: We have demonstrated the suitability of MI in assessing the performance of diagnostic tests, which can facilitate easier interpretation of the true utility of diagnostic tests. Similarly, to the guidance for interpretation of effect size of treatment interventions, we also propose the guidelines for interpretation of the utility of diagnostic tests based on the magnitude of reduction in diagnostic uncertainty.

OBJECTIVE: Lower pre-albumin levels have been associated with increased rates of post-surgical complications, prolonged hospital length of stay (LOS), and death. This study aims to investigate the effect of postoperative pre-albumin levels on perioperative and long-term outcomes following robotic-assisted video thoracoscopic (RAVT) pulmonary lobectomy.

METHODS: We retrospectively reviewed 459 consecutive patients who underwent RAVT pulmonary lobectomy by one surgeon for known or suspected lung cancer. The lowest pre-albumin values during the postoperative hospital stay were recorded. Twenty-three patients with no pre-albumin levels available were excluded from analysis. Patients were grouped as having normal (≥ 15 mg/dL) versus low (< 15mg/dL) pre-albumin. Outcomes and demographics were compared between groups using Pearson χ2, Student's t, or Kruskal-Wallis tests. Univariate and multivariate generalized linear regression, logistic regression, or Cox proportional hazard ratio models were used to assess the association between outcomes and variables of interest. Kaplan-Meier analyses were performed to estimate and depict survival probabilities for each group.

RESULTS: Our study population comprised 436 patients. Lowest postoperative pre-albumin below 15 mg/dL was associated with more postoperative complications (44.2% vs 24.9%, p < 0.001), longer chest tube duration (6.9 vs 4.6 days, p = 0.001), and longer LOS (7.0 vs. 4.4 days, p < 0.001). In survival analysis, lowest perioperative pre-albumin levels were found to correlate with decreased 1 year (p = 0.012), 3-year (p = 0.001), and 5-year survival (p = 0.001).

CONCLUSION: Lower pre-albumin levels postoperatively are associated with more postoperative complications, longer chest tube duration and LOS, and decreased overall survival following robotic-assisted pulmonary lobectomy.

OBJECTIVE: To determine whether scores obtained from Patient Health Questionnaire-9 (PHQ-9) or the General Anxiety Disorder-7 (GAD-7) instruments administered following a concussion can be used to predict recovery time.

METHOD: Retrospective cohort study in a university-based specialty concussion center of 502 concussed participants. Participants completed a PHQ-9 and GAD-7 during their initial visit and subsequent visits during the recovery period (ie, at 14, 28, 56, and 84 days).

RESULTS: The median recovery time from a concussion was 21 days from the initial clinical evaluation; however, individuals with a PHQ-9 score ≤ 6 (n = 262) had a median recovery time of 17 (95% confidence interval [CI] 15-19) days, whereas those with PHQ-9 scores >6 (n = 240) had a median recovery time of 33 (95% CI 28-37) days and a hazard ratio of 0.525 (95% CI 0.438-0.629, P < 0.0001). For individuals with a GAD-7 score ≤ 4 (n = 259), the median recovery was 19 (95% CI 17-21), days whereas for those with a GAD-7 score > 4 (n = 243), the median recovery was 32 (95% CI 28-36) days with a hazard ratio of 0.554 (95% CI 0.462-0.664, P < 0.00).

CONCLUSIONS: Scores obtained from PHQ-9 and GAD-7 screening tools appear to be predictive of an individual's recovery and may help identify those subjects who may benefit from early psychological interventions.

OBJECTIVE: The transfer of peripheral nerves originating above the level of injured spinal cord into the nerves/roots below the injury is a promising approach. It facilitates the functional recovery in lower extremity, bladder/bowel and sexual function in paraplegics. We assessed anatomical feasibility of transfer of lower intercostal nerves to S2 ventral root in human cadaver for management of neurogenic bladder dysfunction in patients with spinal cord injury.

METHODS: Study was performed in five formalin fixed cadavers. Cadavers were placed in prone position. A transverse incision was made along 11th ribs on both sides and 10th, 11th Intercostal nerves (ICN) and subcostal nerve were harvested up to maximum possible length. In four cadavers the ventral root of S2 was exposed by endoscope and in one by the standard open laminectomy. Intercostal nerves were brought down to lumbo-sacral region, S2 ventral root was cut cranially and feasibility of intercostal to S2 anastomosis was assessed.

RESULTS: The mean length of intercostal nerves was 18.4 cm for the 10th 19.5 cm for the 11th and 22.15 cm for the subcostal nerve. The length of harvested nerve and the nerve length necessary to perform sacral roots neurotization were possible in all cases by only by subcostal nerve while T11 and T10 ICN fall short of the required length.

CONCLUSION: For Spinal cord lesions located at the conus, subcostal nerve could be connected to ventral root of S2 in an attempt to restore bladder function while 10th and 11th ICN had enough length to neurotize lumbar plexus.

INTRODUCTION: Interteam performance and Clavien-Dindo (C-D) complications in renal cell carcinoma with inferior vena cava thrombectomy (RCC-IVCT) have not been reported. We aimed to describe complications by the degree of complexity and surgical teams in a collaborative effort between a National Cancer Institute-designated Comprehensive Cancer Center and a Quaternary Care Teaching Hospital.

METHODS: Between January 2011 and May 2019, 73 consecutive RCC-IVCT were included. C-D grades III or higher were captured. Teams involved were urologic-oncology, vascular, hepatobiliary/transplant, and cardiothoracic. The Mayo Clinic tumor thrombus classification was used.

RESULTS: Overall complication rate was 42% (n = 31). Nineteen percent had grade III, 18% had grade IV, and 6% had grade V complications. Patients with level IV thrombus had the highest in-hospital mortality rate (75%). Thrombus level did not show a correlation to complication rates (14% level I, 45% level II, 32% level III, 42% level IV). A positive correlation found between the number of teams involved and complication rates (35% with 2-team, 59% with 3-team, P = .059). Thromboembolic events (6% vs 24%, P = .02) and disposition other than home (22% vs 48%, P = .01) were statistically lower for the 2-team groups. Two-team in-hospital mortality was 1/51 (2%) versus 3-team (3/22,14%, (P = .07). No statistical differences were found in infections, thromboembolic events, and grades of complications between surgical teams.

CONCLUSIONS: Despite similar interteam performance, the consistency of surgeons in high complexity cases could improve outcomes further. Complexity was higher for hepatobiliary/transplant and cardiothoracic teams. A combination of intraoperative events and patient selection (comorbidities and age) contributed to death. Overall, in-hospital mortality was lower than in most reported series.

PURPOSE: Neoadjuvant chemotherapy is a recommended treatment for patients with penile cancer with bulky inguinal lymphadenopathy or unresectable primary tumors, although there is no evidence of its benefit from randomized trials.

MATERIALS AND METHODS: We conducted a systematic search in Embase® and MEDLINE® for studies reporting on patients who received preoperative neoadjuvant chemotherapy for locally advanced penile squamous cell carcinoma. Objective response rate, pathological complete response, grade 3 or greater toxicity and overall mortality were evaluated in terms of neoadjuvant chemotherapy type, which was dichotomized as nontaxane-platinum and taxane-platinum regimens.

RESULTS: Overall 10 studies met the inclusion criteria, enrolling a total of 182 patients, with 66 (36.3%) and 116 (63.7%) treated with nontaxane-platinum and taxane-platinum regimens, respectively. The pooled results demonstrated an objective response rate of 53% (95% CI 42-64), pathological complete response rate of 16%, grade 3 or greater toxicity rate of 40% (95% CI 19-64) and overall mortality of 55% (95% CI 40-70) in patients treated with neoadjuvant chemotherapy. Stratified subanalysis revealed an objective response rate of 55% and 49%, a pathological complete response of 9% and 20%, a toxicity rate of 26% and 49%, and an overall mortality of 54% and 58% for nontaxane-platinum vs taxane-platinum regimens, respectively.

CONCLUSIONS: The pooled findings in this study suggest that approximately 50% of the patients with bulky regional lymph node metastases from penile cancer respond to platinum based neoadjuvant chemotherapy and approximately 16% of patients achieve a pathological complete response. Nontaxane based regimens appear to be better tolerated than taxane regimens based on reported grade 3 or greater adverse events (26% vs 49%). Ultimately the robustness of these observations should be interpreted with an awareness of the inherent limitations of deriving data from a collection of small, heterogeneous series.