BMI is Not Associated with Chest-Specific Body Image, Complications or Revisions in Gender-Affirming Mastectomy: A Single-Center Cross-Sectional Study.

OBJECTIVE: To analyze the impact of Body Mass Index (BMI) on clinical and patient-reported outcomes following gender-affirming mastectomy (GM). BACKGROUND: BMI is a barrier for obese patients seeking GM despite increasing evidence that it is safe in this population. Currently little is known about the impact of BMI on chest-specific body image and satisfaction following GM. METHODS: This single-center, cross-sectional study included individuals 18 years and older who underwent GM between 1990-2020 and were at least 2 years post-operative. Patient-reported chest-specific body image was measured using the BODY-Q and Gender Congruence and Life Satisfaction (GCLS) chest subscales. Satisfaction was measured using the Holmes-Rovner Satisfaction with Decision (SWD) scale. Clinical and demographic variables were identified from chart review. Bivariate analysis was performed to determine if BMI was associated with chest-specific body image, satisfaction, complications within 30 days or revisions in GM. RESULTS: Two hundred twenty-seven individuals meeting eligibility criteria were contacted to participate and one hundred thirty-seven responded (60.4% response rate). The mean age was 29.1 (SD=9.0) and mean BMI was 30.9 (SD=8.0), with 26.4% (N=60) of the cohort having a BMI>35. Chest-specific body image, and satisfaction with decision did not vary by BMI or breast resection weight. Complications and revisions were not associated with BMI. CONCLUSION: Individuals undergoing GM reported high rates of satisfaction following GM regardless of BMI. Complication and revision rates did not vary significantly by BMI or breast resection weight. Surgeons should re-evaluate the role BMI plays in patient selection and counseling for GM.

Long-Term Regret and Satisfaction With Decision Following Gender-Affirming Mastectomy.

Importance: There has been increasing legislative interest in regulating gender-affirming surgery, in part due to the concern about decisional regret. The regret rate following gender-affirming surgery is thought to be approximately 1%; however, previous studies relied heavily on ad hoc instruments. Objective: To evaluate long-term decisional regret and satisfaction with decision using validated instruments following gender-affirming mastectomy. Design, Setting, and Participants: For this cross-sectional study, a survey of patient-reported outcomes was sent between February 1 and July 31, 2022, to patients who had undergone gender-affirming mastectomy at a US tertiary referral center between January 1, 1990, and February 29, 2020. Exposure: Decisional regret and satisfaction with decision to undergo gender-affirming mastectomy. Main Outcomes and Measures: Long-term patient-reported outcomes, including the Holmes-Rovner Satisfaction With Decision scale, the Decision Regret Scale, and demographic characteristics, were collected. Additional information was collected via medical record review. Descriptive statistics and univariable analysis using Fisher exact and Wilcoxon rank sum tests were performed to compare responders and nonresponders. Results: A total of 235 patients were deemed eligible for the study, and 139 responded (59.1% response rate). Median age at the time of surgery was 27.1 (IQR, 23.0-33.4) years for responders and 26.4 (IQR, 23.1-32.7) years for nonresponders. Nonresponders (n = 96) had a longer postoperative follow-up period than responders (median follow-up, 4.6 [IQR, 3.1-8.6] vs 3.6 [IQR, 2.7-5.3] years, respectively; P = .002). Nonresponders vs responders also had lower rates of depression (42 [44%] vs 94 [68%]; P < .001) and anxiety (42 [44%] vs 97 [70%]; P < .001). No responders or nonresponders requested or underwent a reversal procedure. The median Satisfaction With Decision Scale score was 5.0 (IQR, 5.0-5.0) on a 5-point scale, with higher scores noting higher satisfaction. The median Decision Regret Scale score was 0.0 (IQR, 0.0-0.0) on a 100-point scale, with lower scores noting lower levels of regret. A univariable regression analysis could not be performed to identify characteristics associated with low satisfaction with decision or high decisional regret due to the lack of variation in these responses. Conclusions and Relevance: In this cross-sectional survey study, the results of validated survey instruments indicated low rates of decisional regret and high levels of satisfaction with decision following gender-affirming mastectomy. The lack of dissatisfaction and regret impeded the ability to perform a more complex statistical analysis, highlighting the need for condition-specific instruments to assess decisional regret and satisfaction with decision following gender-affirming surgery.

Perceived versus Patient-Reported Significance of Surgeon Gender in Breast Reconstruction.

BACKGROUND: Previous investigators demonstrated that female patients often prefer female providers. However, these studies have not determined whether there are gender preferences for breast reconstruction surgeons or whether the effects of surgeon gender impacts patient-reported outcomes. METHODS: Adult women were crowdsourced using Amazon Mechanical Turk to characterize societal preferences for the gender of breast and plastic surgeons in a hypothetical scenario. The authors also used data from the Mastectomy Reconstruction Outcomes Consortium to determine the association between surgeon gender and patient satisfaction after breast reconstruction. The BREAST-Q questionnaire was used to assess patient-reported outcomes at 3 months and 2 years following reconstruction. Regression analyses were performed to investigate the effects of surgeon gender on patient-reported outcomes. RESULTS: In total, 1413 surveys were collected. Forty-two percent preferred female plastic surgeons, 5 percent preferred male surgeons, and 53 percent reported no preference. The Mastectomy Reconstruction Outcomes Consortium analysis included 2236 patients of 55 male and nine female plastic surgeons. In this cohort, 1921 patients (82.2 percent) had male surgeons, whereas 415 patients (17.8 percent) had female surgeons. Regression analysis at 2 years revealed no differences in satisfaction with surgeon, outcome, or psychosocial well-being. Only satisfaction with information differed, as patients of female surgeons reported greater satisfaction in this category, with an adjusted mean difference of 2.82 (p = 0.018). CONCLUSIONS: Although nonpatient women hypothetically prefer female providers, surgeon gender makes little difference in actual patient satisfaction with breast reconstruction. More investigation is needed to determine whether the difference in information delivery is clinically significant and whether it reflects variations in practices between male and female surgeons. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Comparison of Effective Cost and Complications after Abdominoperineal Resection: Primary Closure versus Flap Reconstruction.

BACKGROUND: Flap reconstruction is recommended for select patients undergoing abdominoperineal resection to mitigate complications. However, the clinical effectiveness and financial implications of flap reconstruction remain unknown. The authors aim to compare the costs and complications for patients undergoing abdominoperineal resection with and without flap reconstruction. METHODS: The Truven MarketScan Databases (2009 to 2016) were used to perform retrospective population-based analysis of colorectal carcinoma patients who underwent abdominoperineal resection with and without flap reconstruction. Univariate and multivariable logistic regressions were used to study effective cost (cumulative cost/number of healthy days) and complications. RESULTS: Of 2557 total abdominoperineal resection patients, 194 patients underwent flap reconstruction. Patients undergoing flap reconstruction had a higher Elixhauser Comorbidity Index (p = 0.004) and were more likely to have local invasion (p < 0.001). At 6 months postoperatively, there were no differences in complications between the two groups (p = 0.116). Flap reconstruction was protective against intraabdominal infections (OR, 0.4; 95 percent CI, 0.2 to 0.9; p = 0.033) but conferred an increased risk of wound complications (OR, 1.5; 95 percent CI, 1.0 to 2.3; p = 0.039). Total median cost of care was similar (abdominoperineal resection alone, $40,050; abdominoperineal resection with flap, $41,380; p = 0.456). Effective cost was greater for abdominoperineal resection alone ($259/healthy day) than abdominoperineal resection with flap ($186/healthy day) but was not statistically significant (p = 0.17). CONCLUSIONS: Patients with flap reconstruction displayed a higher comorbidity score and more extensive disease, but these unfavorable factors did not result in a higher complication rate, total cost, or effective cost. Therefore, flap reconstruction for complex perineal defects confers a benefit in select patients and is a judicious use of health care resources. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Morphometric Evaluation of the Frontal Migraine Trigger Site.

BACKGROUND: Migraine headache has been attributed to specific craniofacial peripheral nerve trigger sites. Some have postulated that hypertrophy of the corrugator muscles causes compression of the supraorbital and supratrochlear nerves, resulting in migraine headache. This study uses morphometric evaluation to determine whether corrugator anatomy differs between patients with migraine headache and control subjects. METHODS: A retrospective review identified patients with and without migraine headache who had a recent computed tomographic scan. Morphometric evaluation of the corrugator supercilii muscles was performed in a randomized and blinded fashion on 63 migraine headache and 63 gender-matched control patients using a three-dimensional image-processing program. These images were analyzed to determine whether corrugator size differed between migraine and control patients. RESULTS: There was no difference in mean corrugator volume or thickness between migraine and control patients. The mean corrugator volume was 1.01 ± 0.26 cm compared with 1.06 ± 0.27 cm in control patients (p = 0.258), and the mean maximum thickness was 5.36 ± 0.86 mm in migraine patients compared with 5.50 ± 0.91 mm in controls (p = 0.359). Similarly, subgroup analysis of 38 patients with frontal migraine and 38 control subjects demonstrated no difference in corrugator size. Further subgroup analysis of nine patients with unilateral frontal migraine showed no difference in corrugator size between the symptomatic side compared with the contralateral side. CONCLUSIONS: Muscle hypertrophy itself does not play a major role in triggering migraine headache. Instead, factors such as muscle hyperactivity or peripheral nerve sensitization may be more causative.

Identification of long-lived proteins retained in cells undergoing repeated asymmetric divisions.

Long-lived proteins have been implicated in age-associated decline in metazoa, but they have only been identified in extracellular matrices or postmitotic cells. However, the aging process also occurs in dividing cells undergoing repeated asymmetric divisions. It was not clear whether long-lived proteins exist in asymmetrically dividing cells or whether they are involved in aging. Here we identify long-lived proteins in dividing cells during aging using the budding yeast, Saccharomyces cerevisiae. Yeast mother cells undergo a limited number of asymmetric divisions that define replicative lifespan. We used stable-isotope pulse-chase and total proteome mass-spectrometry to identify proteins that were both long-lived and retained in aging mother cells after ∼ 18 cells divisions. We identified ∼ 135 proteins that we designate as long-lived asymmetrically retained proteins (LARPS). Surprisingly, the majority of LARPs appeared to be stable fragments of their original full-length protein. However, 15% of LARPs were full-length proteins and we confirmed several candidates to be long-lived and retained in mother cells by time-lapse microscopy. Some LARPs localized to the plasma membrane and remained robustly in the mother cell upon cell division. Other full-length LARPs were assembled into large cytoplasmic structures that had a strong bias to remain in mother cells. We identified age-associated changes to LARPs that include an increase in their levels during aging because of their continued synthesis, which is not balanced by turnover. Additionally, several LARPs were posttranslationally modified during aging. We suggest that LARPs contribute to age-associated phenotypes and likely exist in other organisms.

Werner syndrome gene variants in human sarcomas.

Werner syndrome is an autosomal inherited disease that is characterized by premature aging. The gene mutated in Werner syndrome (WS), WRN, encodes both a 3' --> 5' DNA helicase and a 3' --> 5' DNA exonuclease. Among the WS phenotypes is an exceptionally high incidence of sarcomas. We asked whether spontaneous sarcomas, not known to be associated with WS, also harbor mutations or unreported single nucleotide polymorphisms (SNPs) in WRN. We analyzed RNA or DNA sequences within the helicase and exonuclease domains from 51 and 69 matched sarcoma and adjacent normal tissues, respectively. Among a total of 13 nucleotide variants detected, we identified three novel nonsynonymous substitutions: c.611C>T, c.809_810insT, and c.1882C>G. We further characterized one, c.611C>T, which results in substitution of an evolutionarily conserved proline at amino acid 204 in the exonuclease domain with leucine. We show that P204L WRN exhibits a reduction of WRN exonuclease activity; the specific activity is approximately 10-fold lower than that of wild-type WRN. In contrast, the helicase activity of P204L WRN is reduced less than twofold.

Mutator phenotypes caused by substitution at a conserved motif A residue in eukaryotic DNA polymerase delta.

Eukaryotic DNA polymerase (Pol) delta replicates chromosomal DNA and is also involved in DNA repair and genetic recombination. Motif A in Pol delta, containing the sequence DXXXLYPSI, includes a catalytically essential aspartic acid as well as other conserved residues of unknown function. Here, we used site-directed mutagenesis to create all 19 amino acid substitutions for the conserved Leu(612) in Motif A of Saccharomyces cerevisiae Pol delta. We show that substitutions at Leu(612) differentially affect viability, sensitivity to genotoxic agents, cell cycle progression, and replication fidelity. The eight viable mutants contained Ile, Val, Thr, Met, Phe, Lys, Asn, or Gly substitutions. Individual substitutions varied greatly in the nature and extent of attendant phenotypic deficiencies, exhibiting mutation rates that ranged from near wild type to a 37-fold increase. The L612M mutant exhibited a 7-fold elevation of mutation rate but essentially no detectable effects on other phenotypes monitored; the L612T mutant showed a nearly wild type mutation rate together with marked hypersensitivity to genotoxic agents; and the L612G and L612N strains exhibited relatively high mutation rates and severe deficits overall. We compare our results with those for homologous substitutions in prokaryotic and eukaryotic DNA polymerases and discuss the implications of our findings for the role of Leu(612) in replication fidelity.