Outcomes of enhanced recovery protocols and tranexamic acid on double-incision versus periareolar gender-affirming mastectomy: A retrospective study of postoperative outcomes.

INTRODUCTION: The effects of enhanced recovery protocols and use of tranexamic acid (TXA) to reduce postoperative complications after periareolar and double-incision (DIM) gender-affirming mastectomies have not been previously described. We sought to evaluate the efficacy of our ERP including use of liposomal bupivacaine [Exparel] in these cases, assess the efficacy of TXA in reducing postoperative complications, and compare need for revisionary surgery between periareolar and DI mastectomy techniques. MATERIALS AND METHODS: A retrospective review from November 2017 to June 2022 was performed. Data were collected on patient demographics, operative data, and postoperative outcomes including complications and revisions. Morphine milligram equivalent was used to assess opioid use after surgery. RESULTS: Overall, 260 patients were included: 240 (92.3%) patients in the DI and 20 (7.7%) patients in the periareolar group. Thirty-five (7.3%) breasts in the DIM group and five (12.5%) breasts in the periareolar cohort developed complications (p = 0.220). Significantly more breasts in the periareolar cohort developed hematomas (12.5% vs. 2.9%, p = 0.011). Sixteen (3.3%) breasts in the DIM group developed seromas. Significantly more breasts in the periareolar group required revisionary surgery (15.0% vs. 5.2%, p = 0.025). Patients who received intraoperative liposomal bupivacaine [Exparel] had fewer opioids intraoperatively (p = 0.019) and at discharge (p < 0.001). Use of TXA did not affect rates of complications including hematoma or seroma. CONCLUSIONS: Overall, complication rates for periareolar and DIM are similar. However, the periareolar technique results in a significantly higher rate of hematomas and revisionary surgery. Use of intraoperative liposomal bupivacaine [Exparel] resulted in significantly lower opioid use. Lastly, use of topical TXA did not lower the risk of postoperative hematoma or seroma.

CYP1B1-derived epoxides modulate the TRPA1 channel in chronic pain.

Pain is often debilitating, and current treatments are neither universally efficacious nor without risks. Transient receptor potential (TRP) ion channels offer alternative targets for pain relief, but little is known about the regulation or identities of endogenous TRP ligands that affect inflammation and pain. Here, transcriptomic and targeted lipidomic analysis of damaged tissue from the mouse spinal nerve ligation (SNL)-induced chronic pain model revealed a time-dependent increase in Cyp1b1 mRNA and a concurrent accumulation of 8,9-epoxyeicosatrienoic acid (EET) and 19,20-EpDPA post injury. Production of 8,9-EET and 19,20-EpDPA by human/mouse CYP1B1 was confirmed in vitro, and 8,9-EET and 19,20-EpDPA selectively and dose-dependently sensitized and activated TRPA1 in overexpressing HEK-293 cells and Trpa1-expressing/AITC-responsive cultured mouse peptidergic dorsal root ganglia (DRG) neurons. TRPA1 activation by 8,9-EET and 19,20-EpDPA was attenuated by the antagonist A967079, and mouse TRPA1 was more responsive to 8,9-EET and 19,20-EpDPA than human TRPA1. This latter effect mapped to residues Y933, G939, and S921 of TRPA1. Intra-plantar injection of 19,20-EpDPA induced acute mechanical, but not thermal hypersensitivity in mice, which was also blocked by A967079. Similarly, Cyp1b1-knockout mice displayed a reduced chronic pain phenotype following SNL injury. These data suggest that manipulation of the CYP1B1-oxylipin-TRPA1 axis might have therapeutic benefit.

Preparing for a Crowded Cosmetic Market: A Resident Training Model for Minimally Invasive Cosmetic Treatments.

SUMMARY: Patient demand for nonsurgical and minimally invasive cosmetic treatments has increased in recent years, resulting in a growing market that is particularly vulnerable to specialty creep. Despite this growing demand, nonsurgical cosmetic training for plastic surgery residents is often inconsistent and challenging. To ensure the continued safe and effective delivery of nonsurgical cosmetic care by board-certified plastic surgeons, it is critical to implement standardized training models for plastic surgery residents. In this Special Topic article, the authors describe their experience with a resident-run clinic training model that incorporates graduated autonomy, volunteer patient recruitment, and grant-based industry support that has been successfully implemented at their institution for the past 6 years. The article provides a framework for a resident educational model and addresses common obstacles in resident cosmetic training. The authors also provide recommendations for patient recruitment, optimizing clinic workflow, and the management of patient complications.

Rapid exome sequencing and adjunct RNA studies confirm the pathogenicity of a novel homozygous ASNS splicing variant in a critically ill neonate.

Rapid genomic diagnosis programs are transforming rare disease diagnosis in acute pediatrics. A ventilated newborn with cerebellar hypoplasia underwent rapid exome sequencing (75 h), identifying a novel homozygous ASNS splice-site variant (NM_133436.3:c.1476+1G>A) of uncertain significance. Rapid ASNS splicing studies using blood-derived messenger RNA from the family trio confirmed a consistent pattern of abnormal splicing induced by the variant (cryptic 5' splice-site or exon 12 skipping) with absence of normal ASNS splicing in the proband. Splicing studies reported within 10 days led to reclassification of c.1476+1G>A as pathogenic at age 27 days. Intensive care was redirected toward palliation. Cost analyses for the neonate and his undiagnosed, similarly affected deceased sibling, demonstrate that early diagnosis reduced hospitalization costs by AU$100,828. We highlight the diagnostic benefits of adjunct RNA testing to confirm the pathogenicity of splicing variants identified via rapid genomic testing pipelines for precision and preventative medicine.

An exploration of individual differences in a sample of youth charged with violent sexual and non-sexual crimes.

Youth who engage in violent crime, including sexual offences, remain understudied. Research conducted on adults suggests that factors linked to antisocial and violent behaviour may enhance the current understanding of sexual offences. These factors include a consideration of how dark personality traits (such as psychopathy) and childhood maltreatment may inform the likelihood of sexual offending. Utilizing a sample of juvenile alleged violent offenders (n = 113), the present study examines the construct of adolescent psychopathy, with abuse as a potential moderator, in relation to offence perpetration. Contrary to some of the literature on adults, the findings indicate that neither psychopathy nor experience of abuse differentiates sexual from non-sexual violent offenders. They also suggest that scoring higher on psychopathy relates to violence more broadly. The importance of tailored programming for youth who may be at risk of offending or who require treatment in the justice system is explored.

Novel mutations in NLGN3 causing autism spectrum disorder and cognitive impairment.

The X-linked NLGN3 gene, encoding a postsynaptic cell adhesion molecule, was involved in a nonsyndromic monogenic form of autism spectrum disorder (ASD) by the description of one unique missense variant, p.Arg451Cys (Jamain et al. 2003). We investigated here the pathogenicity of additional missense variants identified in two multiplex families with intellectual disability (ID) and ASD: c.1789C>T, p.Arg597Trp, previously reported by our group (Redin et al. 2014) and present in three affected cousins and c.1540C>T, p.Pro514Ser, identified in two affected brothers. Overexpression experiments in HEK293 and HeLa cell lines revealed that both variants affect the level of the mature NLGN3 protein, its localization at the plasma membrane and its presence as a cleaved form in the extracellular environment, even more drastically than what was reported for the initial p.Arg451Cys mutation. The variants also induced an unfolded protein response, probably due to the retention of immature NLGN3 proteins in the endoplasmic reticulum. In comparison, the c.1894A>G, p.Ala632Thr and c.1022T>C, p.Val341Ala variants, present in males from the general population, have no effect. Our report of two missense variants affecting the normal localization of NLGN3 in a total of five affected individuals reinforces the involvement of the NLGN3 gene in a neurodevelopmental disorder characterized by ID and ASD.

Opioid Prescribing and Consumption Patterns following Outpatient Plastic Surgery Procedures.

BACKGROUND: Opioid overprescribing is a nationwide problem contributing to the current epidemic. This study evaluated opioid consumption, physician prescribing, and patient satisfaction with pain control following outpatient plastic surgery procedures. METHODS: Patients completed a questionnaire during their first postoperative visit. The authors queried about procedure type, quantity of opioids prescribed and consumed, days to opioid cessation, prescription refills, pain scores, use of nonopioid analgesics, and satisfaction with pain control. RESULTS: One hundred seventy patients were included. On average, 26 tablets were prescribed and 13 were consumed. Eighty percent of patients stopped opioids by postoperative day 5. Patients rated their worst pain at 6.1 and follow-up pain at 1.9. Approximately 50 percent of patients consumed nonopioid analgesics. Ninety-six percent of patients were satisfied with their pain control. Similar findings were observed across procedure subcategories. The number of pills prescribed was not correlated with satisfaction but was predictive of worst pain level (p = 0.014). Reduction mammaplasty and abdominoplasty patients consumed the most opioids at 17 and 18.6 pills, respectively; however, first-stage alloplastic breast reconstruction had the largest percentage of patients consuming opioids at the time of follow-up (25 percent) and requiring refills (7 percent). Patients who underwent revision of their reconstructed breast reported the earliest opioid cessation, rated their pain the lowest, and were prescribed the most excess tablets. CONCLUSIONS: Plastic surgeons are prescribing almost double the amount of opioids consumed by patients after outpatient plastic surgery procedures. The results of this study may help guide prescribing practices.

Erratum: Opioid Prescribing and Consumption Trends in Outpatient Plastic Surgery: Erratum.

[This corrects the article DOI: 10.1097/01.GOX.0000533930.73173.70.].

Use of a Surgical Debriefing Checklist to Achieve Higher Value Health Care.

Efforts to improve surgical care by using checklists have been inconsistent in results and not reproducible at scale. The ideal manner for using checklists, along with the time horizon for achieving meaningful and measurable benefits, has been unclear. This article describes a novel process for utilizing debriefing checklists to improve value in surgical care. Debriefings of 54 003 consecutive surgical cases and subsequent analysis of 4523 defects in care by multidisciplinary teams led to rapid-cycle iterative changes in care design and processes. Four dimensions of health care value were achieved: debrief-driven improvements reduced the proportion of surgical cases with reported defects, was associated with a significant reduction in the 30-day unadjusted surgical mortality, lowered costs by substantial gains in efficiency and productivity, and led to a better workforce safety climate. Meaningful and sustained improvements required consistent broad-based teamwork over multiple years, an evidence-based data-driven approach, and senior leader and governance engagement.

Watch Out for Wild Animals: A Systematic Review of Upper Extremity Injuries Caused by Uncommon Species.

BACKGROUND: Across the world, many species of nondomesticated animals dwell among humans in metropolitan areas. Rare animal bites pose a dilemma for hand surgeons, as they often result in operative injuries and recalcitrant infections. The authors treated an 85-year-old man who experienced severe cellulitis of the index finger following an opossum bite. This case prompted a systematic review of upper extremity injuries caused by species other than dogs, cats, snakes, and insects. METHODS: The authors conducted a systematic review of PubMed and Scopus databases to identify relevant articles published between 1980 and 2016. Two reviewers critically appraised the studies that met inclusion and exclusion criteria. RESULTS: The hand infection in the man who sustained an opossum bite at the authors' institution was successfully treated with targeted antibiotic therapy, hand elevation, and splinting. Seventy-one articles met inclusion criteria for and were included in this systematic review. The vast majority of existing articles represent level IV and level V evidence. The relevant literature suggests that the majority of hand infections attributable to animal bites and stings are polymicrobial. CONCLUSIONS: Injuries secondary to aquatic animals appear to be the most frequently described in the literature, and hot water immersion should be used for the majority of envenomation attributable to aquatic species. Infections can often be treated with an aminopenicillin antibiotic combined with a beta-lactamase inhibitor. Given the variability in presentation and potential for sequelae such as soft-tissue necrosis and systemic reactions, hand surgeons should approach such upper extremity injuries with a high degree of caution.

De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy.

X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of ≥20% of transcripts including the known pathogenic haplotypes (i.e. 'LIAVA', 'LVAVA') with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the 'LIAVA' haplotype derived from an ancestral less deleterious 'LIAVS' haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree.

Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicated in Nonsyndromic X-Linked Intellectual Disability due to Mutations in FTSJ1.

tRNA modifications are crucial for efficient and accurate protein synthesis, and modification defects are frequently associated with disease. Yeast trm7Δ mutants grow poorly due to lack of 2'-O-methylated C32 (Cm32 ) and Gm34 on tRNA(Phe) , catalyzed by Trm7-Trm732 and Trm7-Trm734, respectively, which in turn results in loss of wybutosine at G37 . Mutations in human FTSJ1, the likely TRM7 homolog, cause nonsyndromic X-linked intellectual disability (NSXLID), but the role of FTSJ1 in tRNA modification is unknown. Here, we report that tRNA(Phe) from two genetically independent cell lines of NSXLID patients with loss-of-function FTSJ1 mutations nearly completely lacks Cm32 and Gm34 , and has reduced peroxywybutosine (o2yW37 ). Additionally, tRNA(Phe) from an NSXLID patient with a novel FTSJ1-p.A26P missense allele specifically lacks Gm34 , but has normal levels of Cm32 and o2yW37 . tRNA(Phe) from the corresponding Saccharomyces cerevisiae trm7-A26P mutant also specifically lacks Gm34 , and the reduced Gm34 is not due to weaker Trm734 binding. These results directly link defective 2'-O-methylation of the tRNA anticodon loop to FTSJ1 mutations, suggest that the modification defects cause NSXLID, and may implicate Gm34 of tRNA(Phe) as the critical modification. These results also underscore the widespread conservation of the circuitry for Trm7-dependent anticodon loop modification of eukaryotic tRNA(Phe) .

Dietary supplementation with resveratrol protects against striatal dopaminergic deficits produced by in utero LPS exposure.

The purpose of this study was to determine the effect of dietary supplementation with the anti-inflammatory compound resveratrol in pregnant dams on lipopolysaccharide (LPS)-induced dopaminergic deficits in pups exposed to LPS in utero. Gravid female rats were fed with a resveratrol-enriched diet during gestational days 3-22.5 (E3-E22.5) and received an intraperitoneal (i.p.) injection of 1mg/kg LPS at E10.5. The striata were isolated from the pups at postnatal days 10 (P10) and P21. LPS-induced dopaminergic deficits were noted at P21, but not P10. These DA deficits at P21 were exhibited by a loss of DA and DA metabolite [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] levels and tyrosine hydroxylase (TH) expression in the striatum. The LPS-induced loss of DA, DA metabolites, and TH expression were attenuated in the striata of pups from the dams fed with the resveratrol-supplemented diet. These data suggest that a resveratrol-supplemented diet may restore homeostasis of the striatal DA neuronal system following disruption by LPS.

Experience, knowledge, and opinions about childhood genetic testing in Batten disease.

BACKGROUND AND OBJECTIVES: Policies for genetic testing in children (GTIC) focus on medical or psychosocial benefit to the child, discouraging or prohibiting carrier testing, and advising caution regarding pre-symptomatic diagnosis if no treatment exists. This study sought to understand parents' perspectives on these issues and determine their experiences and knowledge related to genetic testing for Batten disease - a set of inherited neurodegenerative diseases of childhood onset for which no disease modifying therapies yet exist. METHODS: Parents of children with Batten disease completed a survey of their knowledge of genetics, experience with genetic testing, and opinions regarding GTIC. RESULTS: 54% had sought genetic testing for non-affected family members, including predictive diagnosis of healthy, at-risk children. Participation in any genetic counseling was associated with greater knowledge on questions about genetics. The majority of parents felt it was better to know ahead of time that a child would develop Batten disease, believed that this knowledge would not alter how they related to their child, and that parents should have the final say in deciding whether to obtain GTIC. CONCLUSIONS: Parents of children with an inherited disease are knowledgeable about genetics and wish to establish predictive or carrier status of at-risk children.

Percutaneous trigeminal rhizotomy in a biplane angiosuite: technical assessment.

BACKGROUND: Percutaneous trigeminal rhizotomy (PTR) uses fluoroscopic guidance to cannulate the foramen ovale for the treatment of trigeminal neuralgia. OBJECTIVE: To describe the use of a high-resolution biplane neuroangiosuite for PTR and retrospectively to assess the performance of this technique. METHODS: From 1990 through 2010, 67 PTRs were performed in 51 patients at our institution; 47 used the c-arm in the operating room (OR) and 20 used the biplane angiosuite. Hospital charts were reviewed for demographics, symptomatology, operative time, number of cannulation attempts, fluoroscopy time and pain outcome. Two-tailed univariate analyses were performed to compare the OR and angiosuite groups. RESULTS: In 20 of 67 PTRs, biplane fluoroscopic guidance in the angiosuite was used. Variations in type of PTR, fluoroscopy technique and follow-up time barred meaningful comparison of these variables between OR and biplane groups. However, the biplane group had significantly fewer mean cannulation attempts (1 vs 2.2, p<0.001). CONCLUSIONS: High-resolution biplane neuroangiosuites offer a readily available alternative to ORs for PTR in the treatment of trigeminal neuralgia. Use of the biplane fluoroscopy machine was practical, safe and at least as effective as the use of the c-arm. It may also offer the advantages of a reduced number of cannulation attempts.

Methodology of clinical research in rare diseases: development of a research program in juvenile neuronal ceroid lipofuscinosis (JNCL) via creation of a patient registry and collaboration with patient advocates.

INTRODUCTION: Juvenile neuronal ceroid lipofuscinosis (JNCL; Batten disease) is a rare, inherited, fatal lysosomal storage childhood disorder. True for many rare diseases, there are no treatments that impact the course of JNCL. The University of Rochester Batten Center's (URBC) mission is to find treatments to slow, halt, or prevent JNCL. OBJECTIVES: Our initial objective was to develop clinical research infrastructure preparatory to clinical trials, establish a JNCL research cohort, construct a disease-specific clinical outcome measure, and validate a non-invasive diagnostic sampling method. The long-term objective is to design and implement JNCL clinical trials. METHODS: The Unified Batten Disease Rating Scale (UBDRS) was developed. The Batten Disease Support and Research Association (BDSRA) referred participants; annual BDSRA meetings provided a mobile research setting for registry enrollment and UBDRS piloting. Neuropsychological examinations were performed, enabling external validation of the UBDRS. Buccal epithelial cell collection for genotyping was introduced. Telemedicine for remote UBDRS assessment was piloted. RESULTS: The registry enrolled 198 families representing 237 children with NCL. The UBDRS was piloted, was validated and has been used to collect natural history data from 120 subjects. Funding and regulatory approval were obtained for a recently launched phase II clinical trial. Several additional lines of inquiry were reported. CONCLUSION: The registry and BDSRA collaboration have enabled development of a clinical rating scale, natural history and neuropsychological studies, and genetic studies for disease confirmation. This work highlights an approach for preparatory natural history research and infrastructure development needed to facilitate efficient implementation of clinical trials in rare diseases.

Females experience a more severe disease course in Batten disease.

Juvenile neuronal ceroid lipofuscinosis (JNCL; CLN3 disease; Batten disease) is an autosomal recessive neurodegenerative disease of childhood. Symptoms typically present at school age with vision loss followed by progressive cognitive decline, motor dysfunction, seizures, and behavior problems. Studies on sex differences in JNCL have yielded mixed results, but parent anecdotes suggest that females experience a more precipitous disease course. Therefore, we sought to determine if sex-based differences exist in JNCL. We used data from the Unified Batten Disease Rating Scale (UBDRS), the Batten Disease Support and Research Association (BDSRA) database, and the PedsQL quality of life (QoL) survey to evaluate sex-based differences in functional independence and time from symptom onset to death. On average, females had JNCL symptom onset one year later and death one year earlier than did males. Despite a later age at onset, females had lower functional capability, earlier loss of independent function, and lower physical QoL. Future research in sex differences in JNCL may help to further understand the biological mechanisms underpinning the disease course and may point to targeted therapies.

High-level 46XX/46XY chimerism without clinical effect in a healthy multiparous female.

Chimerism, when more than one genetically distinct cell line originating in different zygotes is present in a single individual, is a rare event in humans but has been described more than 50 times in the literature. Nearly all the described cases have been detected due to discordance in the cell lines for the sex chromosomes, resulting in an ovotesticular disorder of sexual development. Recently, sex chromosome discordant chimerism detected prenatally has been reported where no phenotypic abnormality was found postnatally. We now report the finding of high-level sex chromosome discordant chimerism in a healthy pregnant 46-year-old female with two previous healthy daughters. 46XX and 46XY cell lines were detected in blood and from the buccal mucosa and chimerism was confirmed by examination of a panel of microsatellite markers. Normal fertility and the presence of female offspring are unique findings in this case and raises the possibility that chimerism with a normal phenotype may be an underappreciated outcome even in the presence of sex chromosome discordance.