Geriatric assessment and medical preoperative screening (GrAMPS) program for older hernia patients.

PURPOSE: The incidence of older adults undergoing inguinal and ventral hernia repairs is increasing. Older adults are disproportionately affected by age-related risk factors, which are often under-recognized and may adversely affect surgical outcomes. These age-related risk factors often termed "geriatric syndromes," include multimorbidity, frailty, cognitive impairment, depression, obesity, functional impairment, polypharmacy, and poor subjective health. The aim of this study was to identify the prevalence of age-related risk factors in older patients undergoing elective hernia repair. METHODS: Patients aged 60 years or older with a planned elective surgical repair of a ventral or inguinal hernia were prospectively enrolled in a clinic. Subjects completed several validated screening tools for geriatric syndromes. RESULTS: Seventy patients completed preoperative assessments (mean age: 68.5 years). In total, 24 (34.3%) screened positive for previously unrecognized objective cognitive impairment (Mini-Cog) and 33 (47.1%) for a subjective memory concern. Sixty patients (85.7%) met criteria for polypharmacy. Additionally, 48 (68.6%) screened positive for either pre-frailty (37, 52.9%) or frailty (11, 15.7%), and 66 (94.3%) had multimorbidity. Twenty-five (35.7%) patients self-rated their health as "poor" or "fair," and 18 (25.7%) patients endorsed some functional impairment. CONCLUSIONS: There is a high prevalence of age-related risk factors in older patients undergoing elective hernia repair. Further, these factors are often unrecognized and underappreciated despite their potential to significantly impact informed consent and shared decision making. Additional study is required to define the impact of these age-related risk factors on surgical outcomes, which will inform preoperative risk assessment and optimization through modifiable risk reduction.

Randomized control trial evaluating the use of a shared decision-making aid for older ventral hernia patients in the Geriatric Assessment and Medical Preoperative Screening (GrAMPS) Program.

PURPOSE: Shared decision making (SDM) is ideally suited to abdominal wall surgery in older adults given the breadth of decision making required by the hernia surgeon and the impact on quality of life (QOL) by various treatment options. Given the paucity of literature surrounding SDM in hernia patients, the feasibility of a novel, formalized SDM aid/tool was evaluated in a pilot randomized trial. METHODS: Patients 60 years or older with a diagnosed ventral hernia were prospectively randomized at an academic hernia center. In the experimental arm, a novel SDM tool, based on the SHARE Approach, guided the consultation. Previously validated SDM assessments and patient's hernia knowledge retention was measured. RESULTS: Eighteen (18) patients were randomized (9 control and 9 experimental). Cohorts were well matched in age (p = 0.51), comorbidities (Charlson Comorbidity Score: p = 0.43) and frailty (mFI-11: p = 0.19; Risk Analysis Index: p = 0.33). Consultation time was 11 min longer in the experimental cohort (p < 0.01). There was a trend towards better Decisional Conflict Scores in the experimental group (p = 0.25) and the experimental cohort had improved post-visit retained hernia knowledge (p < 0.01). All patients in the experimental arm (100%) enjoyed working through the SDM aid/tool and felt it was a worthwhile exercise. CONCLUSION: Incorporating a formalized SDM tool into a busy hernia surgical practice is feasible and well received by patients. In addition, early results suggest it improves retention of basic hernia knowledge and may reduce patient's decisional conflict. Next steps include condensing the SDM tool to enhance efficiency within the clinic and beginning a large, randomized control trial.

P transposon-induced dominant enhancer mutations of position-effect variegation in Drosophila melanogaster.

P transposon induced modifier mutations of position-effect variegation (PEV) were isolated with the help of hybrid dysgenic crosses (pi 2 strain) and after transposition of the mutator elements pUChsneory+ and P[lArB]. Enhancer mutations were found with a ten times higher frequency than suppressors. The 19 pUChsneory(+)- and 15 P[lArB]-induced enhancer mutations can be used for cloning of genomic sequences at the insertion sites of the mutator elements via plasmid rescue. Together with a large sample of X-ray-induced (48) and spontaneous (93) enhancer mutations a basic genetic analysis of this group of modifier genes was performed. On the basis of complementation and mapping data we estimate the number of enhancer genes at about 30 in the third chromosome and between 50 and 60 for the whole autosome complement. Therefore, enhancer of PEV loci are found in the Drosophila genome as frequently as suppressor genes. Many of the enhancer mutations display paternal effects consistent with the hypothesis that some of these mutations can induce genomic imprinting. First studies on the developmentally regulated gene expression of PEV enhancer genes were performed by beta-galactosidase staining in P[lArB] induced mutations.

Promoter is an important determinant of developmentally regulated puffing at the Sgs-4 locus of Drosophila melanogaster.

Sgs-4 is one of the eight known genes coding for larval secretion proteins in Drosophila melanogaster. High-level transcription of the endogenous Sgs genes in salivary glands is accompanied by chromosome puffing at the Sgs gene loci. Naturally occurring mutations of the Sgs-4 promoter region diminish both the level of Sgs-4 expression and the puff size; in null-producers no puff is formed. P element-mediated transformation experiments were performed to clarify this apparent causal relation between transcription and puffing. Sgs-4 upstream sequences, unchanged or recombined with sequences from differently expressed alleles, were fused with Sgs-4 coding and downstream sequences or with the coding sequence of the viral oncogene v-mil. Analyses of the expression of these fragments at the RNA and protein levels and of their capacity for puff formation demonstrate uncoupling of transcription and puffing. That is, high-level transcription is independent of chromosome puffing and does not necessarily induce puffing, and developmentally regulated chromosome puffing is independent of significant transcriptional activity within the puff. Our results show that the strength of the Sgs-4 promoter located within the upstream region from -1 to -840 determines the formation of a puff. No specific effects could be detected on either transcription or puffing by decondensed versus compact chromatin adjoining the transposed DNA at the sites of insertion in transformants. A model in which trans-acting factors binding to the promoter region initiate puffing is proposed.