Publications

2018

Rao, Nikhil G, Ambuj Kumar, Jenny S Wong, Ravi Shridhar, and Dharendra Y Goswami. (2018) 2018. “Effect of a Novel Photoelectrochemical Oxidation Air Purifier on Nasal and Ocular Allergy Symptoms.”. Allergy & Rhinology (Providence, R.I.) 9: 2152656718781609. https://doi.org/10.1177/2152656718781609.

BACKGROUND: Photoelectrochemical oxidation (PECO) is a new air purification technology developed to reduce circulating indoor allergens. PECO removes particles as small as 0.1 nm with the destruction of organic matter otherwise not trapped by a traditional filter and removes volatile organic compounds.

OBJECTIVE: We hypothesized that with daily use, the device would reduce user nasal and ocular allergy total symptom scores (TSS) within 4 weeks.

METHODS: The study was performed among 46 individuals with self-reported allergies using a portable PECO air purifier. Self-reported TSS were calculated at baseline and weekly for 4 weeks following initiation of continuous use of the system. TSS was the sum of total nasal symptom scores (TNSS) and total ocular symptom scores (TOSS) for the week.

RESULTS: There was a statistically significant change in overall TSS from baseline to 4 weeks (10.1 at baseline and 4.35 postintervention) resulting in a mean difference of 5.75 (95% confidence interval [CI] 4.32-7.18; P < .0001). There was a statistically significant change in TNSS from baseline to 4 weeks (6.3 at baseline and 3.04 postintervention) resulting in a mean difference of 3.26 (95% CI 2.33-3.19; P < .0001). There was a statistically significant change in TOSS from baseline to 4 weeks (3.82 at baseline and 1.3 postintervention) resulting in a mean difference of 2.52 (95% CI 1.74-3.3; P < .0001).

CONCLUSION: With the use of PECO air purification technology, TSS, TNSS, and TOSS decreased significantly. These improvements were consistent over the 4-week course of device use.

Lipka, Seth, Ambuj Kumar, and Joel E Richter. (2018) 2018. “PPI Trial for Eosinophilic Esophagitis: Chaos in the Community.”. Journal of Clinical Gastroenterology 52 (7): 590-95. https://doi.org/10.1097/MCG.0000000000000813.

INTRODUCTION: Despite consensus eosinophilic esophagitis (EoE) statement published in 2011 calling for a 2-month trial of protons pump inhibitor (PPI), the guidelines are not followed by many. We studied the practice patterns in our community and response to a PPI retrial in patients previously diagnosed with "idiopathic EoE."

METHODS: All patients presenting to the senior author's practice with suspected EoE from 2011 to 2015. Two cohorts were studied: (1) patients diagnosed in the community as "idiopathic EoE"; (2) treatment naïve patients given a PPI trial at University of South Florida. PPI responsive eosinophilia was defined after 2 months of high dose PPIs after initial diagnosis of mucosal eosinophilia and histologic response of <15 eosinophils per HPF. SPSS v19.0 was used to calculate mean difference and odds ratios (OR) and 95% confidence intervals.

RESULTS: In total, 78 patients met inclusion criteria, 46 patients had outside diagnosis of "idiopathic EoE," and 41 patients received a PPI trial at University of South Florida. In total, 34/46 (73.9%) community patients were placed on a PPI, 3/46 (6.5%) were placed on elimination diets, 31/46 (67.4%) steroids, and 21/46 (45.7%) were treated with both steroids/PPIs. Fewer patients received PPI trials in the community 3/46 (6.5%) versus 26/34 (76.5%) at our center [OR, 46.6 (95% CI, 11.3-191.5); P<0.0001]. In total, 12/26 (46.2%) were PPI responders on our retrial despite previously being diagnosed with idiopathic EoE. The group initially diagnosed at our center had a higher PPI response rate 12/15 (80%) versus 12/26 (46.2%) in the community group [OR, 7.58 (1.42, 40.55; P=0.018)].

CONCLUSIONS: The importance of a PPI trial is misunderstood and may be confused with the more traditional PPI trial for gastroesophageal reflux disease. This algorithm is critical and should be done before empiric steroids/diet therapies.

Dholaria, Bhagirathbhai R, Ernesto Ayala, Lubomir Sokol, Taiga Nishihori, Julio C Chavez, Mohammad Hussaini, Ambuj Kumar, and Mohamed A Kharfan-Dabaja. (2018) 2018. “Allogeneic Hematopoietic Cell Transplantation in T-Cell Prolymphocytic Leukemia: A Single-Center Experience.”. Leukemia Research 67: 1-5. https://doi.org/10.1016/j.leukres.2018.01.009.

BACKGROUND: T- cell prolymphocytic leukemia (T- PLL) is a rare aggressive hematological malignancy. Alemtuzumab, an anti-CD52 humanized monoclonal antibody, is the treatment of choice for remission induction. Allogeneic hematopoietic cell transplantation (allo-HCT) has been described to induce durable remissions and improve survival, but data is limited.

PATIENTS AND METHODS: We evaluated clinical outcomes of 11 patients, median age of 56 (range, 43-71) years who underwent allo-HCT for T-PLL. The majority of cases were in the first complete remission (CR1 = 9, CR2 = 1, second partial response PR2 = 1) at time of allo-HCT. Myeloablative conditioning was the most commonly prescribed preparative regimen (n = 8, 73%) and tacrolimus plus sirolimus was most commonly prescribed regimen for graft-versus-host disease prophylaxis (n = 5, 46%).

RESULTS: The median follow-up for surviving patients was 48 (range, 6-123) months. The 4-year progression-free survival (PFS) and overall survival (OS) were 45% (95% confidence interval (CI) = 13-78%) and 56% (95% CI = 24-89%), respectively. Cumulative incidence of non-relapse mortality (NRM) at 4-year post-transplantation was 34% (95%CI = 14-85%). The 4-year cumulative incidence of relapse/progression was 21% (95% CI = 6-71%).

CONCLUSION: Allo-HCT is an effective treatment for T-PLL. Patients must be evaluated for their candidacy for allo-HCT as soon as the diagnosis is confirmed. Efforts are needed to decrease NRM and relapse.

Charan, Jaykaran, Jagdish Prasad Goyal, Tea Reljic, Patricia Emmanuel, Atul Patel, and Ambuj Kumar. (2018) 2018. “Isoniazid for the Prevention of Tuberculosis in HIV-Infected Children: A Systematic Review and Meta-Analysis.”. The Pediatric Infectious Disease Journal 37 (8): 773-80. https://doi.org/10.1097/INF.0000000000001879.

BACKGROUND: Isoniazid is recommended for prevention of tuberculosis (TB) in HIV-infected adults, but its efficacy in children living with HIV (CLHIV) is not known. We performed a systematic review to assess the efficacy of isoniazid for the prevention of TB in CLHIV.

METHODS: We searched PubMed, Cochrane Clinical Trial Registry and Google Scholar from inception to December 2016. Any randomized controlled trial assessing the role of isoniazid for the prevention of TB in CLHIV was eligible for inclusion. The primary endpoint was TB incidence; secondary end points were mortality, overall survival and severe adverse events. Dual independent extraction of all data was performed. Data were pooled under a random effects model and summarized either as risk ratio (RR) or hazard ratio along with 95% confidence intervals (CIs).

RESULTS: Of 931 references, 3 randomized controlled trials enrolling 977 patients met the inclusion criteria. Pooled results showed a statistically nonsignificant reduction in TB incidence (RR: 0.70; 95% CI: 0.47-1.04; P = 0.07) and mortality (RR: 0.94; 95% CI: 0.39-2.23; P = 0.88) with the use of isoniazid compared with placebo. One study was stopped early because of excess deaths in the placebo arm. However, results from subgroup analysis restricted to only completed trials did not change the overall findings.

CONCLUSIONS: Isoniazid did not reduce the incidence of TB in CLHIV. All included studies were performed in regions with high prevalence of TB making the overall generalizability limited.

Kharfan-Dabaja, Mohamed A, Ambuj Kumar, Facundo E Stingo, Farhad Khimani, Mohammad Hussaini, Ernesto Ayala, Taiga Nishihori, et al. (2018) 2018. “Allogeneic Hematopoietic Cell Transplantation for Richter Syndrome: A Single-Center Experience.”. Clinical Lymphoma, Myeloma & Leukemia 18 (1): e35-e39. https://doi.org/10.1016/j.clml.2017.10.002.

BACKGROUND: Recent studies have shown dismal outcomes when chronic lymphocytic leukemia progresses to Richter syndrome after patients receive ibrutinib, with a median overall survival ranging from 2.6 to 3.5 months. Published data on efficacy of allogeneic hematopoietic cell transplantation in Richter syndrome are limited to single-center case series and registry data.

PATIENTS AND METHODS: We evaluated the efficacy of allogeneic transplantation in 10 patients, median age of 63 (range, 50-74) years, allografted at a median of 5 (range, 4-25) months from diagnosis of Richter syndrome. All showed an objective response to therapy before transplantation (first complete remission = 7 [70%], first partial response = 2 [20%], second partial response = 1 [10%]). Most received a myeloablative conditioning regimen (n = 7, 70%). Filgrastim-mobilized peripheral blood stem cells was the preferred cell source (n = 10, 100%).

RESULTS: Median follow-up of surviving patients was 46 (range, 15-82) months. The 4-year overall survival was 50% (95% confidence interval [CI], 19%-81%). Nonrelapse mortality at 1 year and 4 years post-transplantation were 40% (95% CI, 19%-85%) for both time points. The 4-year incidence of relapse/progression was 10% (95% CI, 2%-64%).

CONCLUSION: Allogeneic hematopoietic cell transplantation is an effective treatment for patients with Richter syndrome who show an objective response before allografting. Patients must be referred to transplant centers as soon as the diagnosis is confirmed to evaluate candidacy for the procedure and identify a suitable donor in a timely manner.

Richter, Joel E, Ambuj Kumar, Seth Lipka, Branko Miladinovic, and Vic Velanovich. (2018) 2018. “Efficacy of Laparoscopic Nissen Fundoplication Vs Transoral Incisionless Fundoplication or Proton Pump Inhibitors in Patients With Gastroesophageal Reflux Disease: A Systematic Review and Network Meta-Analysis.”. Gastroenterology 154 (5): 1298-1308.e7. https://doi.org/10.1053/j.gastro.2017.12.021.

BACKGROUND & AIMS: The effects of transoral incisionless fundoplication (TIF) and laparoscopic Nissen fundoplication (LNF) have been compared with those of proton pump inhibitors (PPIs) or a sham procedure in patients with gastroesophageal reflux disease (GERD), but there has been no direct comparison of TIF vs LNF. We performed a systematic review and network meta-analysis of randomized controlled trials to compare the relative efficacies of TIF vs LNF in patients with GERD.

METHODS: We searched publication databases and conference abstracts through May 10, 2017 for randomized controlled trials that compared the efficacy of TIF or LNF with that of a sham procedure or PPIs in patients with GERD. We performed a network meta-analysis using Bayesian methods under random-effects multiple treatment comparisons. We assessed ranking probability by surface under the cumulative ranking curve.

RESULTS: Our search identified 7 trials comprising 1128 patients. Surface under the cumulative ranking curve ranking indicated TIF had highest probability of increasing patients' health-related quality of life (0.96), followed by LNF (0.66), a sham procedure (0.35), and PPIs (0.042). LNF had the highest probability of increasing percent time at pH <4 (0.99), followed by PPIs (0.64), TIF (0.32), and the sham procedure (0.05). LNF also had the highest probability of increasing LES pressure (0.78), followed by TIF (0.72) and PPIs (0.01). Patients who underwent the sham procedure had the highest probability for persistent esophagitis (0.74), followed by those receiving TIF (0.69), LNF (0.38), and PPIs (0.19). Meta-regression showed a shorter follow-up time as a significant confounder for the outcome of health-related quality of life in studies of TIF.

CONCLUSIONS: In a systematic review and network meta-analysis of trials of patients with GERD, we found LNF to have the greatest ability to improve physiologic parameters of GERD, including increased LES pressure and decreased percent time pH <4. Although TIF produced the largest increase in health-related quality of life, this could be due to the shorter follow-up time of patients treated with TIF vs LNF or PPIs. TIF is a minimally invasive endoscopic procedure, yet based on evaluation of benefits vs risks, we do not recommend it as a long-term alternative to PPI or LNF treatment of GERD.

Lai, Andrew, Seth Lipka, Ambuj Kumar, Sajiv Sethi, David Bromberg, Nanxing Li, Huafeng Shen, Lilia Stefaniwsky, and Patrick Brady. (2018) 2018. “Role of Esophageal Metal Stents Placement and Combination Therapy in Inoperable Esophageal Carcinoma: A Systematic Review and Meta-Analysis.”. Digestive Diseases and Sciences 63 (4): 1025-34. https://doi.org/10.1007/s10620-018-4957-z.

INTRODUCTION: More than 50% of patients with esophageal cancer already have inoperable disease at the time of diagnosis. Controversy surrounds the outcomes of patients with advanced esophageal cancer who receive palliative care by either stent alone or stent plus an additional modality. We set out to perform a systematic review and meta-analysis of studies assessing the use of metal stents as treatment options for symptomatic improvement, survival, and adverse events.

METHODS: We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until January 14, 2016, as well as other databases for randomized controlled trials (RCTs) comparing esophageal stent versus either esophageal stent plus brachytherapy, radiotherapy, or chemotherapy. For quality assurance purposes throughout the systematic review, multiple independent extractions were performed, and the process was executed as per the standards of the Cochrane collaboration. Primary outcomes were mean change in dysphagia score, overall survival, and quality of life. Secondary outcomes were adverse events including fever, severe pain, aspiration, fistula, stent migration, perforation, and restenosis.

RESULTS: Eight RCTs enrolling 732 patients were included with three distinct comparisons: stents combination therapy vs stents alone (5 studies, n = 417), stents alone versus brachytherapy alone (2 studies, n = 274), and stents + brachytherapy vs brachytherapy alone (1 study, n = 41). Stents combination therapy was defined as stents plus radiotherapy, chemotherapy, or both. Mean change in dysphagia scores favored stents combination therapy versus stents alone, and the effect was seen in patients surviving longer than 3 months. Stents combination therapy was also associated with a more favorable overall survival. The risks of stent migration, aspiration pneumonia, and restenosis were lower in the stents combination group compared to stents alone, while the risks of severe pain, hemorrhage, and fistula formation were higher. Changes in dysphagia scores and overall survival did not differ significantly in the brachytherapy-alone vs stents-alone comparison. The risk of fistula formation and hemorrhage were higher in the stents-alone group, while the risk of perforation was lower, compared to brachytherapy alone. Quality of life improvements were seen in all treatment groups, but were not pooled in analysis due to differing methods of measurement.

DISCUSSION: While there appears to be no immediate short-term differences, those who live longer than 3 months experience a significant improvement in dysphagia score using a stents combination therapy approach vs stents alone. The combination therapy significantly improves the overall survival as well as showed improvements in quality of life scores. Larger randomized controlled trials are needed to assess improvements in dysphagia score, overall survival, quality of life, and adverse events.

Kharfan-Dabaja, Mohamed A, Nour Moukalled, Tea Reljic, Jessica El-Asmar, and Ambuj Kumar. (2018) 2018. “Reduced Intensity Is Preferred over Myeloablative Conditioning Allogeneic HCT in Chronic Lymphocytic Leukemia Whenever Indicated: A Systematic Review/Meta-Analysis.”. Hematology/Oncology and Stem Cell Therapy 11 (2): 53-64. https://doi.org/10.1016/j.hemonc.2017.11.001.

Despite availability of new and more effective therapies for chronic lymphocytic leukemia, presently this disease remains incurable unless eligible patients are offered an allogeneic hematopoietic cell transplant. Recent published clinical practice recommendations on behalf of the American Society for Blood and Marrow Transplantation relegated the role of for allogeneic hematopoietic cell transplantation to later stages of the disease. To our knowledge, no randomized controlled trial has been performed to date comparing myeloablative versus reduced intensity conditioning regimens in chronic lymphocytic leukemia patients eligible for the procedure. We performed a systematic review/meta-analysis to assess the efficacy of allogeneic hematopoietic cell transplantation when using myeloablative or reduced intensity conditioning regimens. We report the results in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Based on lower non-relapse mortality and slightly better overall survival rates, reduced intensity conditioning regimens appear to be the most desirable choice whenever the procedure is indicated for this disease. It appears highly unlikely that a RCT will be ever performed comparing reduced intensity vs. myeloablative allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia. In the absence of such a study, results of this systematic review/meta-analysis represent the best available evidence supporting this recommendation whenever indicated in patients with chronic lymphocytic leukemia.

Kuykendall, Lauren, V, Angie Zhang, Bugra Tugertimur, Sara Bijan, Corin Agoris, Ambuj Kumar, and Deniz Dayicioglu. (2018) 2018. “Outcomes in Deep Inferior Epigastric Perforator Flap and Implant-Based Reconstruction: Does Age Really Matter?”. Cancer Control : Journal of the Moffitt Cancer Center 25 (1): 1073274817744603. https://doi.org/10.1177/1073274817744603.

Despite the growing elderly population, there is limited research specific to this demographic concerning breast reconstruction (BR). Lack of evidence-based BR recommendations in older populations may contribute to misconceptions and subsequent underutilization of BR, especially autologous BR. Patients who received either deep inferior epigastric perforator (DIEP) flap BR or tissue expander/implant (TE/I) BR by a single surgeon between July 2011 and July 2015 were surveyed postoperatively by using the psychometrically validated BREAST-Q questionnaire to determine patient satisfaction. Patients were categorized into younger and older cohorts based on median age (55 years) and further stratified based on the type of reconstruction. Of the 311 patients surveyed, 95 patients responded (31% response rate). Overall, younger patients (<55 years old, n = 42) compared with older patients (≥55 years old, n = 53) had significantly higher satisfaction with their outcome (mean difference [MD] 12.06; 95% confidence interval [CI]: 0.96-23.15; P = 0.034). In the TE/I group (n = 58), younger patients had significantly higher satisfaction with breasts (MD: 14.17; 95% CI: 2.58-25.75; P = .017) and outcome (MD: 18.25; 95% CI: 3.95-32.5; P = .010) with fewer complications (odds ratio [OR]: 3.29; 95% CI: 1.37-7.86; P = .010). In the DIEP flap group (n = 55), there was no significant difference inr any of the satisfaction outcomes between younger and older patients. Younger patients tend to be more satisfied and demonstrate fewer complications with implant-based BR. In contrast, both younger and older patients undergoing abdominally based autologous BR were equally satisfied with comparable outcomes.