Publications

2021

Aslam, Sadaf, Jacentha Buggs, Kasey Wyatt, Ambuj Kumar, Ebonie Rogers, and Robert Watson. (2021) 2021. “The Impact of Virtual Crossmatch on Cold Ischemic Times and Outcomes Following Kidney Transplantation.”. The American Surgeon 87 (1): 109-13. https://doi.org/10.1177/0003134820942180.

BACKGROUND: Prolonged cold ischemic time (CIT) in deceased donor kidney transplantation (DDKT) has been associated with adverse graft outcomes. Virtual crossmatch (VXM) facilitates reliable prediction of crossmatch results based on the profile of human leukocyte antigen antibodies of the recipient and the donor in reduced time compared with a physical crossmatch (PXM). We hypothesized a shorter CIT since the implementation of the VXM in recipients of DDKT.

METHODS: We conducted a retrospective cohort study of consecutive adult recipients of DDKT. The data were analyzed for differences in CIT before and after the implementation of VXM.

RESULTS: After the exclusion of 59 recipients (age less than 18 years and/or CIT ≥ 20 hours), our study compared outcomes of 81 PXMs from February to June 2018 against 68 VXMs from February to June 2019. There were no statistical differences between groups based on donor age (P = .09), donor type (P = .38), kidney donor profile index (P = .43), or delayed graft function (P = .20). Recipients with VXM were older (58 vs 51 years, P = .002) and had a higher estimated post-transplant survival score (59% vs 46%, P = .01). The CIT was significantly lower for the VXM group (P = .04).

CONCLUSION: Our study demonstrated a significantly shorter CIT with VXM in DDKT recipients. Our study was limited with small sample size, but the trend of increased graft survival with higher estimated post-transplant scores and older recipients is encouraging as the donor pool expands with marginal kidneys and national sharing.

Kumar, Ambuj, and Robert L Jernigan. (2021) 2021. “Ligand Binding Introduces Significant Allosteric Shifts in the Locations of Protein Fluctuations.”. Frontiers in Molecular Biosciences 8: 733148. https://doi.org/10.3389/fmolb.2021.733148.

Allostery is usually considered to be a mechanism for transmission of signals associated with physical or dynamic changes in some part of a protein. Here, we investigate the changes in fluctuations across the protein upon ligand binding based on the fluctuations computed with elastic network models. These results suggest that binding reduces the fluctuations at the binding site but increases fluctuations at remote sites, but not to fully compensating extents. If there were complete conservation of entropy, then only the enthalpies of binding would matter and not the entropies; however this does not appear to be the case. Experimental evidence also suggests that energies and entropies of binding can compensate but that the extent of compensation varies widely from case to case. Our results do however always show transmission of an allosteric signal to distant locations where the fluctuations are increased. These fluctuations could be used to compute entropies to improve evaluations of the thermodynamics of binding. We also show the allosteric relationship between peptide binding in the GroEL trans-ring that leads directly to the release of GroES from the GroEL-GroES cis-ring. This finding provides an example of how calculating these changes to protein dynamics induced by the binding of an allosteric ligand can regulate protein function and mechanism.

Watts, Stephanie, Joy Gaziano, Ambuj Kumar, and Joel Richter. (2021) 2021. “Diagnostic Accuracy of an Esophageal Screening Protocol Interpreted by the Speech-Language Pathologist.”. Dysphagia 36 (6): 1063-71. https://doi.org/10.1007/s00455-020-10239-3.

Oropharyngeal and esophageal dysphagia may occur simultaneously. However, symptoms are often evaluated separately. Few standardized, multi-texture esophageal screening protocols exist as an addition to the modified barium swallow study (MBSS). Given the gap in MBSS evaluation standards, providers may be lacking information needed to fully assess the swallowing process and create appropriate dysphagia management plans. The aim was to assess the diagnostic accuracy of a standardized esophageal screening protocol performed by an SLP compared to formal reference esophageal examinations. A cross-sectional analytic study was performed. Consecutively referred patients who underwent same-day consultation with the SLP and a gastroenterologist were included. MBSS with a standardized esophageal screen was performed. Same-day formal esophageal testing was completed and included timed barium emptying study or high-resolution manometry. Summary diagnostic accuracy measures were calculated. Seventy-three patients matched the inclusion criteria. Median age was 62.5 years (25-87), 55% were female. Sensitivity of the esophageal screen for the detection of esophageal abnormality was 83.7% (95% CI 70-91.9%); specificity was 73.7% (95% CI 55.6-85.8%). The positive likelihood ratio was 3.14 (95% CI 1.71-5.77), whereas the negative likelihood ratio was 0.22 (95% CI 0.11-0.45). Positive and negative predictive values were 82% and 76%, respectively. Use of a systematic, multi-texture esophageal screen protocol interpreted by SLPs accurately identifies multiphase dysphagia and should be considered in addition to standard MBSS testing. Inclusion of a cursory esophageal view may more adequately assess dysphagia symptoms and help to promote multidisciplinary care.

Le, Nicole K, Sara E Soni, Paul D Smith, Ambuj Kumar, and Deniz Dayicioglu. (2021) 2021. “Preservation of the Implant in Nipple-Sparing Mastectomies: A Retrospective Cohort Study.”. Annals of Plastic Surgery 86 (6S Suppl 5): S491-S494. https://doi.org/10.1097/SAP.0000000000002696.

BACKGROUND: Mastectomies are an integral part of breast cancer treatment for many patients.1 Of those patients, a significant number have previously undergone breast augmentation before being diagnosed with breast cancer. Therefore, we developed the novel technique of performing nipple- and implant-sparing mastectomies (NISMs) for women with prior breast augmentations. This study will assess the plausibility of using NISMs versus nipple-sparing mastectomies (NSMs) in this subgroup of patients by comparing the complication rates.

METHODS: Data were collected on age, tumor size, tumor grade, receptors, and the interval between mastectomy and implant exchange for both groups. Descriptive statistics were used to summarize patient characteristics. Independent samples t tests, χ2 tests, and Fisher exact tests were used to compare the NISM and NSM cohorts. Logistic regression was used to assess the association between complications and mastectomy type and was summarized as an odds ratio with a 95% confidence interval.

RESULTS: Fifteen patients underwent an NISM and 35 patients underwent an NSM. The overall rate of complications was less in NISM cases than in NSM cases (20% vs 27%). However, this difference was not statistically significant (odds ratio, 0.54; 95% confidence interval, 0.18-1.64; P = 0.278).

CONCLUSIONS: The overall complication rate was lower with NISMs compared with NSMs. Nipple- and implant-sparing mastectomy is a novel, viable, and safe option for patients with breast cancer and a history of submuscular breast augmentation.

Munshi, Pashna N, Mehdi Hamadani, Ambuj Kumar, Peter Dreger, Jonathan W Friedberg, Martin Dreyling, Brad Kahl, et al. (2021) 2021. “ASTCT, CIBMTR, and EBMT Clinical Practice Recommendations for Transplant and Cellular Therapies in Mantle Cell Lymphoma.”. Bone Marrow Transplantation 56 (12): 2911-21. https://doi.org/10.1038/s41409-021-01288-9.

Autologous (auto-) or allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities for mantle cell lymphoma (MCL). Recently, chimeric antigen receptor (CAR) T-cell therapy received approval for MCL; however, its exact place and sequence in relation to HCT is unclear. The ASTCT, CIBMTR, and the EBMT, jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-, allo-HCT, and CAR T-cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated; in the first-line setting auto-HCT consolidation represents standard-of-care in eligible patients, whereas there is no clear role of allo-HCT or CAR T-cell therapy, outside of a clinical trial. In the R/R setting, the preferential option is CAR T-cell therapy especially in MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T-cell therapy has failed or is not feasible. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.

Vakos, Amanda, Nadia Khalil, Ambuj Kumar, Lynette Menezes, and Minal Ahson. (2021) 2021. “Assessment of Growth in Pediatric Syrian Refugee Populations in Jordan.”. Avicenna Journal of Medicine 11 (4): 167-71. https://doi.org/10.1055/s-0041-1736544.

Background  Externally displaced pediatric Syrian refugees are at risk of adverse developmental health outcomes in the setting of food insecurity. To evaluate the impact of displacement on nutritional status of Syrian children, this study describes the prevalence of malnutrition of Syrian children residing in Jordan. Methods  A retrospective cross-sectional analysis of data from patient records < 18 years of age from the Syrian American Medical Society's (SAMS) January 2019 mission trip to Jordan was performed. Prevalence of stunting, severe wasting, wasting, overweight, and underweight were calculated using the World Health Organization (WHO) definitions. Results  Overall, 392 Syrian children were included. In the 0 to 59 months group ( n  = 191), prevalence of stunting was 13.9% ( n  = 165), severe wasting 4.2% ( n  = 165), wasting 6% ( n  = 165), overweight 16.4% ( n  = 165), and underweight 5.3% ( n  = 190). In the > 59 months group ( n  = 201), prevalence of stunting was 7.2% ( n  = 194), severe wasting 3.6% ( n  = 194), wasting 5.2% ( n  = 194), overweight 6.7% ( n  = 194), and underweight 4.6% ( n  = 153). Age group was significantly associated with stunting (odds ratio [OR]  = 2.08,9 5% CI 1.03 to 4.19) and overweight (OR = 2.72; 95% CI 1.36 to 5.47) with increased odds of each in the 0-59 months group. Conclusion  The findings suggest evidence of higher prevalence of malnutrition in Syrian children compared with prior assessments and greater impact on the younger cohort. In 0 to 59 months' old Syrian children, stunting and wasting were of medium severity and overweight was of high severity. This may reflect food insecurity in the setting of ongoing conflict, strain on resources, and evolving refugee policies, acknowledging study limitations. Syrian refugee children living in Jordan experience wasting and stunting. Comprehensive assessment of current nutritional status of Syrian children is needed. Access to adequate and nutritious food is paramount.

Aslam, Sadaf, Jacentha Buggs, Samantha Melo, Aizara Ermekbaeva, Ebonie Rogers, Robert Shaw, Ambuj Kumar, and Nyingi Kemmer. (2021) 2021. “The Association Between Alcoholic Liver Disease and Alcohol Tax.”. The American Surgeon 87 (1): 92-96. https://doi.org/10.1177/0003134820945223.

BACKGROUND: The incidence of alcoholic liver disease (ALD) has increased, causing it to become a primary indication for liver transplantation in the United States. We hypothesized an association between alcohol taxation and prevalence of ALD.

METHODS: We conducted a retrospective study of united network for organ sharing (UNOS) waitlist additions for liver transplantation between January 2007 and December 2016. We also analyzed the average excise tax (2007-2016) for beer, wine, and spirits in listing states of liver transplant waitlist additions (LTWA).

RESULTS: There were 104 805 adult UNOS LTWA with assigned diagnoses, an annual increase from 22% to 28%. There were 24 316 LTWA with ALD diagnosis. The mean value for beer tax was significantly lower for ALD patients than for non-ALD patients across all age groups (P < .001). The analysis demonstrated significantly more ALD in waitlisted patients 35-54 years of age (30%), compared with 18-34 years (10%) and ≥55 years (20%), P < .001. The data confirmed significantly more ALD Medicaid patients in the 35-54 year age group (28%) compared with other age groups, P < .001.

DISCUSSION: Our research demonstrated an association between lower beer tax and higher ALD prevalence across all age groups. We found a larger percentage of middle-aged (35-54 years) Medicaid patients listed with ALD. These findings raise the need for further investigation of a potential public health concern for an association between ALD and beer tax, especially for middle-aged patients of lower socioeconomic status.

Holt, Lauren, Madeline H Carney, Lauren Duncanson, Christopher Hazen, Ambuj Kumar, Bri Anne McKeon, and Laurie Woodard. (2021) 2021. “Perceived Barriers to Gynecologic Care by Women Who Use Wheelchairs.”. Cureus 13 (6): e15647. https://doi.org/10.7759/cureus.15647.

Objective The aim of this study was to evaluate the current barriers associated with gynecologic care as perceived by women who use wheelchairs. Methods This qualitative study evaluated the barriers to gynecologic healthcare as described by female wheelchair users. We recruited English-speaking female participants aged 18 years and older who primarily used a wheelchair for mobility through flyer and email distribution. Interviews were conducted by three investigators using a semi-structured interview guide and recorded for transcription. Two investigators reviewed all transcriptions for accuracy which were then coded to identify emergent themes. Results The thematic saturation was achieved with 16 interviews. The most common barrier cited was transferring to the exam table (n=16). Women reported that their providers lacked knowledge and experience with women who use wheelchairs (n= 11). Conclusion There are many barriers to gynecologic care for women who use wheelchairs. Interventions are needed to improve accessibility to care for women who use wheelchairs.

Alhamad, Moath M A, Ambuj Kumar, Hala Chaaban, Karen M Wickline, and Thao T B Ho. (2021) 2021. “Platelets and Immature Neutrophils in Preterm Infants With Feeding Intolerance.”. American Journal of Perinatology 38 (11): 1150-57. https://doi.org/10.1055/s-0040-1710555.

OBJECTIVE: Feeding intolerance (FI) is a common presentation of necrotizing enterocolitis (NEC) and sepsis. NEC and sepsis are associated with hematological changes, but these changes alone are not reliable biomarkers for early diagnosis. This study examined whether the combination of hematological indices and FI can be used as an early diagnostic tool for NEC or sepsis.

STUDY DESIGN: This retrospective cohort study included infants born at <1,500 g or <30 weeks who had symptoms of FI. The exclusion criteria were congenital or chromosomal disorders, thrombocytopenia or platelet transfusion before the onset of FI, and history of bowel resection. We compared the hematological indices from infants with pathologic FI (due to NEC or sepsis) to infants with benign FI.

RESULTS: During the study period, 211 infants developed FI; 185 met the inclusion criteria. Infants with pathologic FI (n = 90, 37 cases with NEC and 53 with sepsis) had lower birth gestational age and weight compared with 95 infants with benign FI (n = 95). Pathologic FI was associated with lower platelet count (median 152 × 103/μL vs. 285 × 103/μL, p < 0.001) and higher immature-to-total neutrophil (I/T) ratio (median 0.23 vs. 0.04, p < 0.001) at the onset of FI. Pathologic FI was also associated with a decrease in baseline platelets compared with an increase in benign FI. For diagnosis of pathologic FI, a decrease ≥10% in platelets from baseline had a sensitivity and specificity of 0.64 and 0.73, respectively, I/T ratio ≥0.1 had a sensitivity and specificity of 0.71 and 0.78, respectively, and the combination of both parameters had a sensitivity and specificity of 0.50 and 0.97, respectively.

CONCLUSION: FI caused by NEC or sepsis was associated with a decrease in platelets from baseline, and a lower platelet level and higher I/T ratio at the onset of FI. These findings can help clinicians in the management of preterm infants with FI.

KEY POINTS: · FI is a common presentation of NEC and sepsis in preterm infants.. · FI due to NEC or sepsis is associated with changes in platelets and I/T ratio.. · These changes could be useful as early markers for diagnosis..