AEBP1 encodes the aortic carboxypeptidase-like protein (ACLP) that associates with collagens in the extracellular matrix (ECM) and has several roles in development, tissue repair, and fibrosis. ACLP ...is expressed in bone, the vasculature, and dermal tissues and is involved in fibroblast proliferation and mesenchymal stem cell differentiation into collagen-producing cells. Aebp1−/− mice have abnormal, delayed wound repair correlating with defects in fibroblast proliferation. In this study, we describe four individuals from three unrelated families that presented with a unique constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of Ehlers-Danlos syndrome (EDS). Analysis of skin biopsies revealed decreased dermal collagen with abnormal collagen fibrils that were ragged in appearance. Exome sequencing revealed compound heterozygous variants in AEBP1 (c.1470delC p.Asn490_Met495delins(40) and c.1743C>A p.Cys581∗) in the first individual, a homozygous variant (c.1320_1326del p.Arg440Serfs∗3) in the second individual, and a homozygous splice site variant (c.1630+1G>A) in two siblings from the third family. We show that ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that bi-allelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive EDS subtype.
Abstract Cisplatin is a platinum-based chemotherapeutic agent that induces peripheral neuropathy in 30% of patients. Peripheral neuropathy is the dose limiting side effect, which has no preventative ...therapy. We have previously shown that cisplatin induces apoptosis in dorsal root ganglion (DRG) sensory neurons by covalently binding to nuclear DNA (nDNA), resulting in DNA damage, subsequent p53 activation and Bax-mediated apoptosis via the mitochondria. We now demonstrate that cisplatin also directly binds to mitochondrial DNA (mtDNA) with the same binding affinity as nDNA. Cisplatin binds 1 platinum molecule per 2166 mtDNA base pairs and 1 platinum molecule per 3800 nDNA base pairs. Furthermore, cisplatin treatment inhibits mtDNA replication as detected by 5-bromo-2′-deoxy-uridine (BrdU) incorporation and inhibits transcription of mitochondrial genes. The relative reduction in mtDNA transcription is directly related to the distance the gene is located from the transcription initiation point, which implies that randomly formed platinum adducts block transcription. Cisplatin treated DRG neurons exhibit mitochondrial vacuolization and degradation in vitro and in vivo. Taken together, this data suggests that direct mtDNA damage may provide a novel, distinct mechanism for cisplatin-induced neurotoxicity separate from the established nDNA damage pathway.
The surgical treatment of breast cancer has been associated with negative consequences for patients' body image, sexual functioning, mental health, and social adjustment. Recent advances in the ...surgical approach to breast cancer allow the oncologic surgeon to safely optimize cosmetic outcomes. Little is known about the possible relevance of surgical scars. The aim of this research was to gather the perspective of breast cancer survivors themselves on the issue of surgical scars and their negative impact on survivorship.
An internet survey was conducted nationwide in the United States among women who reported being surgically treated by lumpectomy, mastectomy, or both procedures for breast cancer. To improve generalizability, census-based enrollment quotas were applied for geographic region, health insurance, and income.
The five hundred respondents reported lumpectomy only (n = 215), mastectomy only (n = 140), or both surgeries (n = 132). In response to the statement, "I do not like the location of my surgical scar", 64% of lumpectomy-only respondents and 67% of mastectomy-only respondents agreed somewhat or strongly. Only 26% of lumpectomy respondents and 14% of mastectomy respondents reported minimal or no negative impact as a consequence of the surgical scars.
Consistent with previous literature, this nationwide US survey shows that the majority of women feel negatively affected by their breast cancer surgery scars. Surgeons should consider this outcome when planning surgery, which may improve patients' survivorship journey.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
We sought to better understand breast-specific sensuality (BSS) in sexually inactive breast cancer survivors.
Methods
We conducted an anonymous cross-sectional survey of breast cancer ...survivors during surveillance appointments from 2014 to 2016. Sexual inactivity was defined as no sexual activity within 4 weeks prior. Categorical data were analyzed using Fisher’s exact test. Multiple logistic regression adjusted for age and menopausal status, and Firth’s bias correction accommodated sparse data.
Results
Of 585 respondents, 546 (93.3%) were between the ages of 40 and 79 years, of whom 285 (48.7%) were sexually inactive. Favorable post-treatment appearance satisfaction was reported by 413 (71.0%) respondents. Sexually inactive respondents were more likely to score discomfort with their partner seeing their chest after surgery compared with sexually active respondents (41 20.4% vs. 34 11.4%;
p
= 0.002). Both sexually inactive and active respondents reported that their chest was important in intimacy after surgery but at significantly different rates (117 44.3% vs. 217 72.6%;
p
< 0.001). Post-surgical appearance satisfaction for sexually inactive respondents was positively associated with level of comfort with partner seeing their chest after surgery (
p
< 0.001) and with rating of a pleasurable caress of the treated breast (
p
< 0.001).
Conclusions
Over 40% of sexually inactive respondents reported their chest was important in intimacy after surgery, suggesting that BSS may be a route to intimacy for sexually inactive breast cancer survivors. Post-surgical breast appearance satisfaction significantly correlated with comfort being seen by one’s partner and appreciation of a pleasurable breast caress. Optimizing breast cancer surgical aesthetic outcomes may improve survivorship.
Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by defects in the branched-chain α-ketoacid dehydrogenase complex, which results in elevations of the branched-chain amino ...acids (BCAAs) in plasma, α-ketoacids in urine, and production of the pathognomonic disease marker, alloisoleucine. The disorder varies in severity and the clinical spectrum is quite broad with five recognized clinical variants that have no known association with genotype. The classic presentation occurs in the neonatal period with developmental delay, failure to thrive, feeding difficulties, and maple syrup odor in the cerumen and urine, and can lead to irreversible neurological complications, including stereotypical movements, metabolic decompensation, and death if left untreated. Treatment consists of dietary restriction of BCAAs and close metabolic monitoring. Clinical outcomes are generally good in patients where treatment is initiated early. Newborn screening for MSUD is now commonplace in the United States and is included on the Recommended Uniform Screening Panel (RUSP). We review this disorder including its presentation, screening and clinical diagnosis, treatment, and other relevant aspects pertaining to the care of patients.
Purpose
More early-staged breast cancer patients are choosing mastectomy. No studies have addressed breast-specific sensuality (BSS), defined as the breast’s role during intimacy. We explored BSS ...among women undergoing lumpectomy (L), mastectomy alone (M), or with reconstruction (MR) and analyzed the association of surgical modality with sexual function.
Methods
Women undergoing breast cancer surgery between 2000 and 2013 were eligible for survey using investigator-generated questions and the Female Sexual Function Index (FSFI). Demographic and surgical data were collected by chart review. The Kruskal–Wallis test was used to analyze FSFI scores, and
χ
2
or Fisher’s exact tests were used for categorical data.
Results
Of 453 invited participants, 268 (59%) completed the survey. Of these, 69.4, 22.4, and 8.2% underwent L, MR, or M, respectively. The importance of the breast/chest wall during intimacy declined significantly regardless of surgical modality (L 83–74%,
p
= 0.0006; M 95–47%,
p
= 0.003; MR 93–77%,
p
= 0.002). No difference in sexual function was found between L, MR, and M (median FSFI score 28.2, 27.5, 25.9, respectively;
p
= 1.0). Comparing L versus MR, higher FSFI scores resulted with appearance satisfaction (29.0 vs. 22.6
p
= 0.002) and preserved BSS as pleasurable breast caress (28.8 vs. 26.5,
p
= 0.04) and the breast as part of intimacy (28.8 vs. 24.8,
p
= 0.1).
Conclusions
Breast cancer surgery is associated with lowered BSS. However, BSS and appearance satisfaction scores are better for L and appear to correlate with improved sexual function postoperatively. These data may guide surgical counseling and contribute to survivorship outcomes.
Purpose
The skin and/or nipple-sparing approach has become an oncologically sound and desirable choice for women choosing mastectomy. Indocyanine green (ICG) perfusion imaging has been shown to ...reduce ischemic complications in mastectomy skin flaps. Immediate reconstruction requires a well-vascularized skin flap capable of tolerating full expansion. Identification of the perforating subcutaneous vessels to the skin envelope may allow for better and more consistent blood vessel preservation and flap perfusion.
Methods
The authors conducted an institutional review board-approved prospective study with 41 patients to assess the feasibility of using ICG perfusion imaging to visualize, cutaneously map, and preserve the vessels that supply the skin flap and nipple-areolar complex. For each patient, the number of vessels initially mapped, the number of vessels preserved, the extent to which each vessel was preserved, and the proportion of the flap with adequate perfusion (as defined by the SPY-Q > 20% threshold) was recorded and analyzed.
Results
Vessels were able to be identified and marked in a high majority of patients (90%). There was a moderate linear relationship between the number of vessels marked and the number preserved. Successful mapping of vessels was associated with lower rates of wound breakdown (
p
= 0.036). Mapping and preserving at least one vessel led to excellent flap perfusion (> 90%). No increase in complications was observed from utilizing ICG angiography preoperatively.
Conclusion
This prospective study using preoperative ICG perfusion mapping demonstrated safety, feasibility, and good prognostic outcomes.
Level of evidence
III.
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