Amanda M. Gutierrez

Causes and Prevalence of Unplanned Readmissions After Colorectal Surgery:: A Systematic Review and Meta-Analysis

A systematic review and meta‐analysis of the current literature was conducted to compare the overall and cause‐specific readmission rates after colorectal surgery of older adults with those of younger individuals. Potential predictors of unplanned readmission were also identified. Estimated pooled readmission rates were calculated and reported as pooled proportions with associated 95% confidence intervals (CI) in 60,131 total readmissions; 11.0% (95% CI = 10.0–12.0) of all admissions after colorectal surgery resulted in unplanned readmission at 30 days. Older adults had a lower rate of readmission than younger individuals. Bowel obstruction was the most common cause of unplanned readmission, accounting for 33.4% of all unplanned readmissions, followed by surgical site infection (15.7%) and intraabdominal abscess (12.6%). Several age‐related predictors of unplanned readmission were identified, such as poor functional capacity, multiple comorbidities, chronic obstructive pulmonary disease, and discharge to a nonhome destination. The findings of this review will help guide the development of future interventions to reduce preventable readmissions after colorectal surgery in older adults.

Cysteine mutagenesis improves the production without abrogating antigenicity of a recombinant protein vaccine candidate for human chagas disease

ABSTRACT A therapeutic vaccine for human Chagas disease is under development by the Sabin Vaccine Institute Product Development Partnership. The aim of the vaccine is to significantly reduce the parasite burden of Trypanosoma cruzi in humans, either as a standalone product or in combination with conventional chemotherapy. Vaccination of mice with Tc24 formulated with monophosphoryl-lipid A (MPLA) adjuvant results in a Th1 skewed immune response with elevated IgG2a and IFNγ levels and a statistically significant decrease in parasitemia following T. cruzi challenge. Tc24 was therefore selected for scale-up and further evaluation. During scale up and downstream process development, significant protein aggregation was observed due to intermolecular disulfide bond formation. To prevent protein aggregation, cysteine codons were replaced with serine codons which resulted in the production of a non-aggregated and soluble recombinant protein, Tc24-C4. No changes to the secondary structure of the modified molecule were detected by circular dichroism. Immunization of mice with wild-type Tc24 or Tc24-C4, formulated with E6020 (TLR4 agonist analog to MPLA) emulsified in a squalene-oil-in-water emulsion, resulted in IgG2a and antigen specific IFNγ production levels from splenocytes that were not significantly different, indicating that eliminating putative intermolecular disulfide bonds had no significant impact on the immunogenicity of the molecule. In addition, vaccination with either formulated wild type Tc24 or Tc24-C4 antigen also significantly increased survival and reduced cardiac parasite burden in mice. Investigations are now underway to examine the efficacy of Tc24-C4 formulated with other adjuvants to reduce parasite burden and increase survival in pre-clinical studies.

Parental Perspectives on Whole-Exome Sequencing in Pediatric Cancer: A Typology of Perceived Utility

Purpose To explore how parents of pediatric cancer patients perceived the utility of clinical tumor and germline whole-exome sequencing (WES) results. Patients and Methods We conducted longitudinal interviews with parents of a diverse pediatric cancer population before disclosure of WES results (n=64), then one to eight months (n=33) after disclosure. Interview transcripts were analyzed using a thematic qualitative approach. Results Parents identified a broad range of types of utility for their childs WES results. Even when results did not affect their childs current treatment, they expressed optimism about future clinical utility for their child, themselves, and other family members. Parents also reported experiencing psychological utility including peace of mind, relief of guilt, and satisfaction of curiosity. Pragmatic utility, such as the ability to plan for the future and make better reproductive decisions, was also described. Conclusion Parents of pediatric cancer patients perceive WES to have broad utility, including psychological and pragmatic utility, even if there is no direct impact on clinical care. Further work will need to consider how the value of genomic information should be characterized, how risks and benefits should be described, and how these results should inform recommendations and decisions about using WES.

Do privacy and security regulations need a status update? Perspectives from an intergenerational survey

Background The importance of health privacy protections in the era of the “Facebook Generation” has been called into question. The ease with which younger people share personal information about themselves has led to the assumption that they are less concerned than older generations about the privacy of their information, including health information. We explored whether survey respondents’ views toward health privacy suggest that efforts to strengthen privacy protections as health information is moved online are unnecessary. Methods Using Amazon’s Mechanical Turk (MTurk), which is well-known for recruitment for survey research, we distributed a 45-item survey to individuals in the U.S. to assess their perspectives toward privacy and security of online and health information, social media behaviors, use of health and fitness devices, and demographic information. Results 1310 participants (mean age: 36 years, 50% female, 78% non-Hispanic white, 54% college graduates or higher) were categorized by generations: Millennials, Generation X, and Baby Boomers. In multivariate regression models, we found that generational cohort was an independent predictor of level of concern about privacy and security of both online and health information. Younger generations were significantly less likely to be concerned than older generations (all P < 0.05). Time spent online and social media use were not predictors of level of concern about privacy or security of online or health information (all P > 0.05). Limitations This study is limited by the non-representativeness of our sample. Conclusions Though Millennials reported lower levels of concern about privacy and security, this was not related to internet or social media behaviors, and majorities within all generations reported concern about both the privacy and security of their health information. Thus, there is no intergenerational imperative to relax privacy and security standards, and it would be advisable to take privacy and security of health information more seriously.

Portero versus portador: Spanish interpretation of genomic terminology during whole exome sequencing results disclosure

AIM Describe modifications to technical genomic terminology made by interpreters during disclosure of whole exome sequencing (WES) results. PATIENTS & METHODS Using discourse analysis, we identified and categorized interpretations of genomic terminology in 42 disclosure sessions where Spanish-speaking parents received their childs WES results either from a clinician using a medical interpreter, or directly from a bilingual physician. RESULTS Overall, 76% of genomic terms were interpreted accordantly, 11% were misinterpreted and 13% were omitted. Misinterpretations made by interpreters and bilingual physicians included using literal and nonmedical terminology to interpret genomic concepts. CONCLUSION Modifications to genomic terminology made during interpretation highlight the need to standardize bilingual genomic lexicons. We recommend Spanish terms that can be used to refer to genomic concepts.

Reconciling newborn screening and a novel splice variant in BTD associated with partial biotinidase deficiency: a BabySeq Project case report

Here, we report a newborn female infant from the well-baby cohort of the BabySeq Project who was identified with compound heterozygous BTD gene variants. The two identified variants included a well-established pathogenic variant (c.1612C>T, p.Arg538Cys) that causes profound biotinidase deficiency (BTD) in homozygosity. In addition, a novel splice variant (c.44+1G>A, p.?) was identified in the invariant splice donor region of intron 1, potentially predictive of loss of function. The novel variant was predicted to impact splicing of exon 1; however, given the absence of any reported pathogenic variants in exon 1 and the presence of alternative splicing with exon 1 absent in most tissues in the GTEx database, we assigned an initial classification of uncertain significance. Follow-up medical record review of state-mandated newborn screen (NBS) results revealed an initial out-of-range biotinidase activity level. Levels from a repeat NBS sample barely passed cutoff into the normal range. To determine whether the infant was biotinidase-deficient, subsequent diagnostic enzyme activity testing was performed, confirming partial BTD, and resulted in a change of management for this patient. This led to reclassification of the novel splice variant based on these results. In conclusion, combining the genetic and NBS results together prompted clinical follow-up that confirmed partial BTD and informed this novel splice sites reclassification, emphasizing the importance of combining iterative genetic and phenotypic evaluations.