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Antisense oligodeoxynucleotides (ASOs) prevent expression of proteins by binding to specific regions of mRNA. This report investigates a potential lipid-based delivery system for ASO. A hydrophobic complex was recovered following addition of cationic lipids to ASOs in a Bligh and Dyer monophase [chloroform/methanol/water (1:2.1:1, v/v/v)]. The addition of monovalent cationic lipids (dioleyldimethylammonium chloride, dimethyldioctadecylammonium bromide, dioleoyltrimethylammonium propane), resulted in >95% recovery of the ASOs from the organic phase when ASO phosphate charge was neutralized. Cholesteryldimethylaminoethylcarbamate mediated efficient extraction at a charge ratio (+/-) >5.2. ASOs could not be extracted into the organic phase by the polyvalent lipids, dioctadecylamidoglycyl spermine and 2,3-dioleyloxy- N -[2(sperminecarboxamido)ethyl]- N , N -dimethyl-1-propaminium trifluoroacetate, even at a charge ratio (+/-) >5. Dioleoylphosphatidylethanolamine, but not dioleoylphosphatidylcholine, prevented formation and destabilized the hydrophobic complexes. The characterization of the hydrophobic complex led to the development of lipid-ASO particles containing dioleyldimethylammonium chloride, dioleoylphosphatidylethanolamine and poly(ethylene glycol)-conjugated phosphatidylethanolamine (LAPs). When FITC-labeled ASOs in LAPs were added to B-cell lymphoma cells (DoHH2) in vitro , cell-associated ASO decreased as poly(ethylene glycol)-conjugated phosphatidylethanolamine incorporation increased. Western Blot analysis demonstrated that no significant downregulation of Bcl-2 protein was observed when using LAPs. The results suggest that the use of stabilized PEG-conjugated lipids may be detrimental for cationic lipid-based ASO delivery. [ABSTRACT FROM AUTHOR]

Introduction: Failure of alloplastic breast reconstruction is an uncommon occurrence that may result in abandonment of reconstructive efforts or salvage with conversion to autologous reconstruction. The purpose of this study was to identify factors that predict failure of alloplastic breast reconstruction and conversion to autologous reconstruction. Methods: A retrospective chart review was conducted of patients who underwent mastectomy and immediate alloplastic breast reconstruction between 2008 and 2019. Inclusion criteria included patients 18 years or older who underwent initial alloplastic reconstruction with a minimum of 3-year follow-up. Data collected included age, body mass index, cancer type, surgical characteristics, neo/adjuvant treatment details, and complications. Results were analyzed using Fischer's exact test, t -test, and multivariate logistic regression. Results: A total of 234 patients met inclusion criteria. Of those, 23 (9.8%) required conversion from alloplastic to autologous reconstruction. Converted patients had a mean age of 50.1 ± 8.5. The time from initial alloplastic reconstruction to conversion was 30.7 months. The most common reasons for conversion included soft tissue deficiency (48%), infection (30%), and capsular contracture (22%). Patients were converted to deep inferior epigastric perforator flap (DIEP; 52%), latissimus dorsi flap with implant (26%), and DIEP with implant (22%). Multivariate logistic regression modeling identified radiation (OR 8.4 [CI = 1.7-40.1]) and periprosthetic infection (OR 14.6 [CI = 3.4-63.8]) as predictors for conversion. Conclusions: Among patients undergoing mastectomy with immediate alloplastic breast reconstruction, those treated with radiation have 8.4 greater odds of conversion and those with a periprosthetic infection have 14.6 greater odds for conversion to an autologous reconstruction., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 The Author(s).)

Purpose: Understanding the variables that influence success in digital replant surgery is essential to guide clinical decision-making and to counsel patients. The purpose of this study was to determine the replant success rate and identify predictors of success at our tertiary care centre. Methods: This was a single centre, retrospective cohort study of consecutive patients who underwent digital replantation from January 2000 to September 2018. Adult patients with flexor zone I to III amputations were included. Patient demographics, comorbidities, injury pattern, operative data, and post-operative care were reviewed. The primary outcome was survival of the replanted digit at discharge. Results: A total of 146 patients met inclusion criteria. Of these, 100 had single-digit replants and 46 underwent multi-digit replants for a total of 220 digits. The success rate was 71%. Predictors of success included sharp mechanism of injury (P < .01), incomplete amputation (P < .01), amputation proximal to zone I flexor level (P = .02), post-operative acetylsalicylic acid use (P < .01), absence of leech use (P = .05), and absence of operative re-exploration (P < .01). Daytime replants had similar outcome compared to nighttime replants despite having increased ischemia time (7.9 ± 3.9 hours vs 6.8 ± 2.6 hours, P = .02). However, daytime operative time (7.8 ± 3.7 hours) was significantly shorter than nighttime replant time (9.6 ± 5.9 hours, P = .01). Conclusion: Sharp amputation, intact venous drainage, proximal amputation, and acetylsalicylic acid use were associated with replant survival and are factors to consider when managing patients for digital replantation. Leech therapy and operative re-exploration were associated with poor outcome. Nighttime replants required significantly longer operative time than daytime replants despite similar survival outcome., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 The Author(s).)

Introduction and Purpose: Breast reconstruction is an active area of plastic surgery research. Citation analysis allows for quantitative analysis of publications, with more citations presumed to indicate greater influence. We performed citation analysis to evaluate the most cited papers on breast reconstruction between 2000 to 2010 to identify contemporary research trends. Methods: The SCI-EXPANDED database was used to identify the 50 most cited papers. Data points included authorship, publication year, publication journal, study design, level of evidence, number of surgeons/institutions, center of surgery, primary outcome assessed, implant/flap/acellular dermal matrix/fat graft, acellular dermal matrix brand and use with implants/flaps, fat graft use with implants/flaps, unilateral/bilateral, one-/two-stage, immediate/delayed, number of patients/procedures, complications. Descriptive analysis of trends was performed based on results. Results: 20% of papers were published in 2006, 16% in 2007 and 12% in both 2004/2009. 66% were published in Plastic and Reconstructive Surgery . The majority were retrospective or case series, and of Level III or IV evidence. The one Level I study was a prospective multicenter trial. 21 and 7 papers discussed procedures by single/multiple surgeons, respectively. Results from single/multiple centers were discussed in 18 and 6 papers, respectively. 30 papers discussed implant-based reconstruction, 22 papers flap-based (19 microsurgical), 15 papers acellular dermal matrix, and five papers fat grafting. The primary focus in the majority was complications or outcomes. Conclusion: Our analysis demonstrates continually evolving techniques in breast reconstruction. However, there is notable lack of high quality evidence to guide surgical decision-making in the face of increasing surgical options., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 The Author(s).)

Background: Mastectomy flap necrosis is a common complication of immediate breast reconstruction that impacts recovery time and reconstructive success. Nitroglycerin ointment is a topical vasodilator that has been shown to improve skin flap survival in an animal model. The objective of this study was to evaluate whether the application of nitroglycerin ointment to the breast skin after mastectomy and immediate reconstruction causes a decrease in the rate of mastectomy flap necrosis compared with placebo., Methods: This study was conducted as a randomized controlled trial and included patients aged 21 to 69 years undergoing mastectomy and immediate breast reconstruction at the University of British Columbia-affiliated hospitals (Vancouver, British Columbia, Canada). Patients with a medical history that precluded the administration of nitroglycerin were excluded from the study. The target sample size was 400 patients. Nitroglycerin ointment (45 mg) or a placebo was applied to the mastectomy skin at the time of surgical dressing., Results: The trial was stopped at the first interim analysis after 165 patients had been randomized (85 to the treatment group and 80 to the placebo group). Mastectomy flap necrosis developed in 27 patients (33.8 percent) receiving placebo and in 13 patients (15.3 percent) receiving nitroglycerin ointment; the between-group difference was 18.5 percent (p = 0.006; 95 percent CI, 5.3 to 31.0 percent). Postoperative complications were similar in both groups [nitroglycerin, 22.4 percent (19 of 85); placebo, 28.8 percent (23 of 80)]., Conclusions: In patients undergoing mastectomy and immediate reconstruction, there was a marked reduction in mastectomy flap necrosis in patients who received nitroglycerin ointment. Nitroglycerin ointment application is a simple, safe, and effective way to help prevent mastectomy flap necrosis., Clinical Question/level of Evidence: Therapeutic, I.

Background: Direct-to-implant single-stage immediate breast reconstruction using acellular dermal matrix is a cost-effective alternative to two-stage expander-implant reconstruction. The purpose of this study was to identify predictors of direct-to-implant single-stage immediate breast reconstruction failure, defined as need for early (≤6 months) revision surgery., Methods: The authors conducted a retrospective cohort study of all patients with direct-to-implant single-stage immediate breast reconstruction in 2010 and 2011 at three University of British Columbia hospitals. Data were compared between successful and failed single-stage reconstructions. Predictors of failure were identified using multivariate logistic regression. Patient demographics and complications were compared to a random sample of control patients with two-stage alloplastic reconstruction without acellular dermal matrix., Results: Of 164 breasts that underwent direct-to-implant single-stage immediate breast reconstruction, 52 (31.7 percent) required early revision. Increasing breast cup size was the only significant predictor of early revision compared with bra size A (OR for bra size B, 4.86; C, 4.96; D, 6.01; p < 0.05). Prophylactic mastectomies showed a trend toward successful single stage (OR, 0.47; p = 0.061), whereas smoking history trended toward failure (OR, 1.79; p = 0.065). Mastectomy flap necrosis was significantly higher in direct-to-implant single-stage immediate reconstruction cases compared to two-stage controls., Conclusions: Direct-to-implant breast reconstruction can be reliably performed in a single stage in patients with small breast size. Increasing breast cup size confers a higher chance of early revision. A two-stage approach may be more cost-effective in larger breasted patients., Clinical Question/level of Evidence: Risk, III.

Background & Objectives: It is not known if optimism influences regret following major reconstructive breast surgery. We examined the relationship between dispositional optimism, major complications and decision regret in patients undergoing microsurgical breast reconstruction., Methods: A consecutive series of 290 patients were surveyed. Independent variables were: (1) dispositional optimism and (2) major complications. The primary outcome was Decision Regret. A multivariate regression analysis determined the relationship between the independent variables, confounders and decision regret., Results: Of the 181 respondents, 63% reported no regret after breast reconstruction, 26% had mild regret, and 11% moderate to severe regret. Major complications did not have a significant effect on decision regret, and the impact of dispositional optimism was not significant in Caucasian women. There was a significant effect in non-Caucasian women with less optimism who had significantly higher levels of mild regret 1.36 (CI 1.02-1.97) and moderate to severe regret 1.64 (CI 1.0-93.87)., Conclusions: This is the first paper to identify a subgroup of non-Caucasian patients with low dispositional optimism who may be at risk for developing regret after microsurgical breast reconstruction. Possible strategies to ameliorate regret may involve addressing cultural and language barriers, setting realistic expectations, and providing more support during the pre-operative decision-making phase., (© 2013 Wiley Periodicals, Inc.)

Background: The two-stage tissue expander/implant (TE/I) reconstruction is currently the gold standard method of implant-based immediate breast reconstruction in North America. Recently, however, there have been numerous case series describing the use of one-stage direct to implant reconstruction with the aid of acellular dermal matrix (ADM). In order to rigorously investigate the novel application of ADM in one-stage implant reconstruction, we are currently conducting a multicentre randomized controlled trial (RCT) designed to evaluate the impact on patient satisfaction and quality of life (QOL) compared to the two-stage TE/I technique., Methods/designs: The MCCAT study is a multicenter Canadian ADM trial designed as a two-arm parallel superiority trial that will compare ADM-facilitated one-stage implant reconstruction compared to two-stage TE/I reconstruction following skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) at 2 weeks, 6 months, and 12 months. The source population will be members of the mastectomy cohort with stage T0 to TII disease, proficient in English, over the age of 18 years, and planning to undergo SSM or NSM with immediate implant breast reconstruction. Stratified randomization will maintain a balanced distribution of important prognostic factors (study site and unilateral versus bilateral procedures). The primary outcome is patient satisfaction and QOL as measured by the validated and procedure-specific BREAST-Q. Secondary outcomes include short- and long-term complications, long-term aesthetic outcomes using five standardized photographs graded by three independent blinded observers, and a cost effectiveness analysis., Discussion: There is tremendous interest in using ADM in implant breast reconstruction, particularly in the setting of one-stage direct to implant reconstruction where it was previously not possible without the intermediary use of a temporary tissue expander (TE). This unique advantage has led many patients and surgeons alike to believe that one-stage ADM-assisted implant reconstruction should be the procedure of choice and should be offered to patients as the first-line treatment. We argue that it is crucial that this technique be scientifically evaluated in terms of patient selection, surgical technique, complications, aesthetic outcomes, cost-effectiveness, and most importantly patient-reported outcomes before it is promoted as the new gold standard in implant-based breast reconstruction., Trial Registration: ClinicalTrials.gov: NCT00956384.

The secretory antibody responses to M. pneumoniae polypeptides were assessed among human breast milk samples. M. pneumoniae polypeptides were resolved with conventional SDS-PAGE, and antibody responses were determined by immunoblotting. Antibodies that contained secretory component were found to recognize antigens of 200, 185, 170, 150, 135, 92, 85, 60, 43, 27, and 24 kDa (M(r)). Among the latter, antigens of 170, 150, 60, and 43 kDa were recognized from the majority. Although these antibody binding sites parallel those that are also generally recognized by human sera when equivalent antigen is used, the high frequency (80%) of 150 kDa antigen recognition is not common for serum responses. This antigen should be further explored for its potential in future assessments of component vaccines.