Publications

2020

Buggs, Jacentha, Sadaf Aslam, Chelsea Walker, Madison Hook, Tiffany M Matyja, Ebonie Rogers, Samantha Nyce, Diego Patiño, Ambuj Kumar, and Nyingi Kemmer. (2020) 2020. “Pre-Liver Transplant Coronary Artery Disease Workup for Low-Risk Patients.”. The American Surgeon 86 (8): 976-80. https://doi.org/10.1177/0003134820942169.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of mortality following orthotopic liver transplant, yet there is no standardized protocol for pre-liver-transplant coronary artery disease assessment. The main objective of this study was to determine the agreement between 2 methods of cardiac risk assessment: dobutamine stress echocardiogram (DSE) and coronary calcium score (CCS) and to determine which test was best able to predict coronary calcification in low-risk patients.

METHODS: A retrospective study was performed using the medical records of 436 patients who received cardiac clearance for a liver transplant. A total of 152 patients' medical records were included based on the inclusion of patients who had received both DSE and CCS. A kappa coefficient was calculated to determine the agreement between the DSE and CCS results. In addition, the positive predictive values (PPVs) of both the CCS and DSE along with cardiac catheterization indicating abdominal occlusion were analyzed to compare the accuracy of the 2 tests.

RESULTS: It was determined that there was a 12% agreement between DSE results and CCS. It was found that the DSE had a PPV of 56% and the CCS had a PPV of 80%.

CONCLUSION: From this data, it was concluded that there was no agreement between the results of the CCS and the DSE. While neither the CCS nor the DSE presents an optimal method of risk assessment, the CCS had a much higher PPV and was therefore determined to be the more accurate test.

Ho, Thao T B, Ambuj Kumar, Adetola F Louis-Jacques, Larry J Dishaw, Alyson L Yee, and Maureen W Groër. (2020) 2020. “The Development of Intestinal Dysbiosis in Anemic Preterm Infants.”. Journal of Perinatology : Official Journal of the California Perinatal Association 40 (7): 1066-74. https://doi.org/10.1038/s41372-020-0599-z.

OBJECTIVE: Anemia and Proteobacteria-dominant intestinal dysbiosis in very low birth weight (VLBW) infants have been linked to necrotizing enterocolitis, a severe gut inflammatory disease. We hypothesize that anemia of prematurity is related to the development of intestinal dysbiosis.

STUDY DESIGN: Three hundred and forty-two weekly stool samples collected prospectively from 80 VLBW infants were analyzed for bacterial microbiomes (with 16S rRNA). Linear mixed-effects model was used to determine the relationships between the onsets of anemia and intestinal dysbiosis.

RESULTS: Hematocrit was associated with intestinal microbiomes, with lower Hct occurring with increased Proteobacteria and decreased Firmicutes. Infants with a hematocrit <30% had intestinal microbiomes that diverged toward Proteobacteria dominance and low diversity after the first postnatal month. The microbiome changes were also related to the severity of anemia.

CONCLUSIONS: This finding supports a potential microbiological explanation for anemia as a risk factor for intestinal dysbiosis in preterm infants.

Khade, Pranav M, Ambuj Kumar, and Robert L Jernigan. (2020) 2020. “Characterizing and Predicting Protein Hinges for Mechanistic Insight.”. Journal of Molecular Biology 432 (2): 508-22. https://doi.org/10.1016/j.jmb.2019.11.018.

The functioning of proteins requires highly specific dynamics, which depend critically on the details of how amino acids are packed. Hinge motions are the most common type of large motion, typified by the opening and closing of enzymes around their substrates. The packing and geometries of residues are characterized here by graph theory. This characterization is sufficient to enable reliable hinge predictions from a single static structure, and notably, this can be from either the open or the closed form of a structure. This new method to identify hinges within protein structures is called PACKMAN. The predicted hinges are validated by using permutation tests on B-factors. Hinge prediction results are compared against lists of manually curated hinge residues, and the results suggest that PACKMAN is robust enough to reproduce the known conformational changes and is able to predict hinge regions equally well from either the open or the closed forms of a protein. A group of 167 protein pairs with open and closed structures has been investigated Examples are shown for several additional proteins, including Zika virus nonstructured (NS) proteins where there are 6 hinge regions in the NS5 protein, 5 hinge regions in the NS2B bound in the NS3 protease complex and 5 hinges in the NS3- helicase protein. Results obtained from this method can be important for generating conformational ensembles of protein targets for drug design. PACKMAN is freely accessible at (https://PACKMAN.bb.iastate.edu/).

Yadav, Yad Ram, Shailendra Ratre, Vijay Parihar, Jitin Bajaj, Mallika Sinha, and Ambuj Kumar. (2020) 2020. “Endoscopic Management of Chronic Subdural Hematoma.”. Journal of Neurological Surgery. Part A, Central European Neurosurgery 81 (4): 330-41. https://doi.org/10.1055/s-0039-1698388.

BACKGROUND:  Twist drill evacuation, burr hole aspiration, mini-craniotomy, and craniotomy are some of the surgical methods to remove chronic subdural hematoma (CSDH). Endoscopic treatment was also recently found to be useful.

METHODS:  We conducted a prospective study of 72 hematomas in 68 patients. Computed tomography was performed in all cases. Endoscopic surgery was performed in all CSDH patients.

SURGICAL PROCEDURE:  A 4-cm skin incision was performed at the most curved part of skull with the CSDH. A mini-craniotomy or enlarged burr hole was made. The inner and outer table of the burr hole margin was drilled to provide a straight trajectory to the hematoma cavity. An endoscope supported by a telescope holder was used. A modified silicone brain retractor was used in five patients. A subgaleal drain was left in all patients for 3 to 5 days.

RESULTS:  There were 42 male and 26 female patients. The age ranged from 45 to 79 years (average: 69 years). All patients had a history of head trauma. Preoperative average Glasgow Coma Scale Score was 14. The procedure was effective in hematoma evacuation and a good visualization of the whole cavity in all patients. The endoscopic technique helped in complete hematoma removal in organized/solid clot, septations, and bridging vessels in 17, 2, and 2 cases, respectively. Duration of surgery ranged from 35 to 80 minutes. One death occurred. There was no recurrence, infection, fresh bleed, or injury to the brain or membrane.

CONCLUSION:  The endoscopic technique is an effective alternative technique for treating CSDH. Although the study has limitations because of the small number of patients with a short follow-up, the study indicated that thick and vascular membranes, septations, and organized and solid clots can be removed effectively using this technique.

Azizi, Mounsif, Ahmet M Aydin, Ali Hajiran, Andrew Lai, Ambuj Kumar, Charles C Peyton, Suks Minhas, et al. (2020) 2020. “Reply by Authors.”. The Journal of Urology 203 (6): 1155. https://doi.org/10.1097/JU.0000000000000746.03.
Ledford, Robert, Alfred Burger, Jeff LaRochelle, Farina Klocksieben, Deborah DeWaay, and Kevin E O’Brien. (2020) 2020. “Exploring Perspectives from Internal Medicine Clerkship Directors in the USA on Effective Narrative Evaluation: Results from the CDIM National Survey.”. Medical Science Educator 30 (1): 155-61. https://doi.org/10.1007/s40670-019-00825-y.

PURPOSE: Clinical performance evaluations play a critical role in determining medical school clerkship grades. This study aimed to provide clarification from clerkship directors in internal medicine on what constitutes an effective and informative narrative description of student performance.

METHODS: In September 2016, the Clerkship Directors in Internal Medicine (CDIM) electronically administered its annual, voluntary, and confidential cross-sectional survey of its US membership. One section of the survey asked six questions regarding the helpful components of an effective narrative evaluation. Respondents were asked to rate the effectiveness of elements contained within narrative evaluations of students.

RESULTS: Ninety-five CDIM members responded to the survey with an overall response rate of 74.2%. Descriptions of skills and behaviors were felt to be the most important, followed by a description of the overall synthetic or global assessment level of the student. Descriptions of personality and attitude were the next highest rated feature followed by adjectives describing performance. Length was felt to be the least important component. In free-text comments, several respondents indicated that direct observation of performance and specific examples of skills and behaviors are also desirable.

CONCLUSIONS: Narrative evaluations of students that explicitly comment on skills, behaviors, and an overarching performance level of the learner are strongly preferred by clerkship directors. Direct observation of clinical performance and giving specific examples of such behaviors give evaluations even more importance. Faculty development on evaluation and assessment should include instruction on these narrative assessment characteristics.

Song, Ethan Y, Puja Venkat, Michael Fradley, Jessica M Frakes, Farina Klocksieben, Jacques Fontaine, Rutika Mehta, Sabrina Saeed, Sarah E Hoffe, and Jose M Pimiento. (2020) 2020. “Clinical Factors Associated With the Development of Postoperative Atrial Fibrillation in Esophageal Cancer Patients Receiving Multimodality Therapy before Surgery.”. Journal of Gastrointestinal Oncology 11 (1): 68-75. https://doi.org/10.21037/jgo.2019.12.05.

BACKGROUND: The incidence of esophageal cancer (EC) is increasing in the USA. Neoadjuvant therapy for locally advanced cancers followed by surgical resection is the standard of care. The most common post-esophagectomy cardiac complication is atrial fibrillation (AF). New-onset postoperative AF can require a prolonged hospital stay and may confer an overall poorer prognosis. In this study, we seek to identify clinical factors associated with postoperative AF.

METHODS: Query of an IRB approved database of 1,039 esophagectomies at our institution revealed 677 patients with EC from 1999 to 2017 who underwent esophagectomy after neoadjuvant treatment. Age, treatment location (primary vs. other), gender, neoadjuvant radiation type [2D vs. 3D vs. intensity modulated radiation therapy (IMRT)], radiation dose, surgery type (transthoracic vs. transhiatal vs. three field), smoking history, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), operative time, blood transfusions, fluid management, and length of stay (LOS) were analyzed in relationship to the development of AF. Statistical analysis was performed with SPSS 24.

RESULTS: The mean age of the entire cohort was 64.3 (range, 28-86 years), with a Caucasian and male preponderance (White: 94.5%; male: 83.6%). Of the 677 patients, 14.9% (n=101) developed postoperative AF. Increasing age (P<0.001), increased radiation dose (P=0.034), operative time (P=0.001), and blood transfusions (P=0.027) were associated with AF. LOS was longer in patients with AF than those without AF (10.5 vs. 10.0 days, P=0.001). On multivariate analysis, increasing age (95% CI: 1.023-1.080, P<0.001) and radiation dose (95% CI: 1.000-1.001, P=0.034) remained significant. None of the other parameters assessed were associated with the development of AF.

CONCLUSIONS: Increasing age and radiation dose were associated with the development of postoperative AF in this cohort. This study suggests that older patients or patients receiving higher radiation dose should be monitored more closely in the postoperative setting and potentially referred earlier preoperatively for cardio-oncology assessment. Future study is required to determine if modification of current radiation techniques and cardiac dose constraints in this patient population may be warranted.

Iqbal, Madiha, Tea Reljic, Farina Klocksieben, Taimur Sher, Ernesto Ayala, Hemant Murthy, Ali Bazarbachi, Ambuj Kumar, and Mohamed A Kharfan-Dabaja. (2020) 2020. “Corrigendum to ’Efficacy of Allogeneic HCT in HTLV-1 Associated Adult T-Cell Leukemia/Lymphoma: Results of a Systematic Review/Meta-Analysis’ [Biology of Blood and Marrow Transplantation 25/8 (2019) 1695-1700].”. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation 26 (1): 209-12. https://doi.org/10.1016/j.bbmt.2019.09.014.
Song, Ethan Y, Jessica M Frakes, Martine Extermann, Farina Klocksieben, Rutika Mehta, Sabrina Saeed, Sarah E Hoffe, and Jose M Pimiento. (2020) 2020. “Clinical Factors and Outcomes of Octogenarians Receiving Curative Surgery for Esophageal Cancer.”. The Journal of Surgical Research 251: 100-106. https://doi.org/10.1016/j.jss.2020.01.002.

BACKGROUND: The incidence of esophageal cancer is increasing in the United States. Although neoadjuvant therapy (NAT) for locally advanced cancers followed by surgical resection is the standard of care, there are no clearly defined guidelines for patients aged ≥79 y.

METHODS: Query of an institutional review board-approved database of 1031 esophagectomies at our institution revealed 35 patients aged ≥79 y from 1999 to 2017 who underwent esophagectomy. Age, gender, tumor location, histology, clinical stage, Charlson Comorbidity Index (CCI), NAT administration, pathologic response rate to NAT, surgery type, negative margin resection status, postoperative complications, postoperative death, length of stay, 30- and 90-d mortality, and disease status parameters were analyzed in association with clinical outcome.

RESULTS: The median age of the octogenarian cohort was 82.1 y with a male preponderance (91.4%). American Joint Committee on Cancer clinical staging was stage I for 20% of patients, stage II for 27% of patients, and stage III for 50% of patients, which was not statistically significant compared with the younger cohort (P = 0.576). Within the octogenarian group, 54% received NAT compared with 67% in the younger group (P = 0.098). There was no difference in postoperative complications (P = 0.424), postoperative death (P = 0.312), and recurrence rate (P = 0.434) between the groups. However, CCI was significantly different between the octogenarian and nonoctogenarian cohort (P = 0.008), and octogenarians had shorter overall survival (18 versus 62 mo, P<0.001). None of the other parameters assessed were associated with clinical outcomes.

CONCLUSIONS: Curative surgery is viable and safe for octogenarians with esophageal cancer. Long-term survival was significantly shorter in the octogenarian group, suggesting the need for better clinical selection criteria for esophagectomy after chemoradiation and that identification of complete responders for nonoperative management is warranted.

Patel, Atul, Kinjal Shah, Mitkumar Dharsandiya, Ketan Patel, Tushar Patel, Mukesh Patel, Tea Reljic, and Ambuj Kumar. (2020) 2020. “Safety and Efficacy of Tocilizumab in the Treatment of Severe Acute Respiratory Syndrome Coronavirus-2 Pneumonia: A Retrospective Cohort Study.”. Indian Journal of Medical Microbiology 38 (1): 117-23. https://doi.org/10.4103/ijmm.IJMM_20_298.

BACKGROUND: Cytokine release storm (CRS) in severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is thought to be the cause for organ damage and death which is independent of the actual viral burden. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, is approved for the treatment of CRS. We describe the efficacy and safety of TCZ in SARS CoV-2 pneumonia.

METHODS: This retrospective study was conducted at a tertiary care hospital from April 20 2020 to May 21 2020. The primary endpoint was the cumulative incidence of a composite of either need for admission to the intensive care unit (ICU) with invasive mechanical ventilation or death. Safety outcomes included an increase in liver transaminases and/or evidence of infection.

RESULTS: A total of 20 patients received TCZ during the study period. The median age was 54 years (95% confidence interval [CI] 47-63). About 85% of the patients were male. Nearly 70% of the patients had at least one comorbidity. About 55% required ICU admission. The median duration of ICU stay was 11 days (95% CI: 3-13 days). The cumulative incidence of the requirement for mechanical ventilation, clinical improvement and mortality was 11% (95% CI: 0.03%-1%), 74% (95% CI 37%-89%) and 25% (95% CI: 11%-63%), respectively. There was no difference in outcomes according to age, gender or computed tomography severity score. Asymptomatic transaminitis was the most common drug reaction (55%), and one patient developed bacteraemia.

CONCLUSIONS: TCZ is likely a safe and effective modality of treatment for improving clinical and laboratory parameters of SARS CoV-2 patients with a reduction in ICU stay and ventilatory care need.