Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net).

INTRODUCTION: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. METHODS: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. RESULTS: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. CONCLUSION: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.

An Evaluation of the Utility of the Breast Reconstruction Risk Assessment Score Risk Model in Prepectoral Tissue Expander Breast Reconstruction.

INTRODUCTION: Individualized postsurgical risk assessment models provide surgeons and patients with information that is vital to the surgical decision-making process. One such tool, the Breast Reconstruction Risk Assessment (BRA) score, uses a limited selection of patient-specific factors to predict 30-day postsurgical risk of surgical site infection, seroma, dehiscence, reoperation and explantation associated with immediate submuscular tissue expander breast reconstruction. This model's performance in prepectoral tissue expander reconstruction has not been previously reported. Here, we evaluate the performance of the BRA score model in a population of patients who underwent immediate prepectoral tissue expander breast reconstruction. MATERIALS AND METHODS: A retrospective chart review was conducted of prepectoral breast reconstructions performed in 2 institutions between January 2017 and December 2018. Complications occurring within 30 days postoperatively were documented and compared with the BRA score predicted risk for each patient. RESULTS: Overall 247 patients (average age, 49.2 years) were included in the study. The mean BRA score predicted 30-day risk of a complication was 13.0% (7.5-41.5%). The observed rate of 30-day postoperative complications was 31.2% (77 patients), though only 36 (14.6%) patients had complications included in the model. The remaining patients experienced skin necrosis or hematoma as their only early complication. The 30-day BRA score model demonstrated good fit for the overall occurrence of any of the BRA score predicted complications (Hosmer-Lemeshow 0.7167), though the model discrimination was poor (C statistic <0.60). Notably, half of the 30-day postsurgical complications observed in this study were due to skin necrosis, a complication not currently included in the 30-day BRA score model. CONCLUSIONS: Our results indicate that the current 30-day BRA score model may have poor predictive value in prepectoral breast reconstruction. The most common early complication observed, skin necrosis, is not currently included in the model, suggesting that caution should be applied when using this risk predictive calculator as an adjunct to patient evaluation and counseling.

Impact of Postoperative Antibiotic Prophylaxis Duration on Surgical Site Infections in Autologous Breast Reconstruction.

BACKGROUND: Although some surgeons prescribe prolonged postoperative antibiotics after autologous breast reconstruction, evidence is lacking to support this practice. We used the Tracking Operations and Outcomes for Plastic Surgeons database to evaluate the association between postoperative antibiotic duration and the rate of surgical site infection (SSI) in autologous breast reconstruction. STUDY DESIGN: The intervention of interest for this study was postoperative duration of antibiotic prophylaxis: either discontinued 24 hours after surgery or continued beyond 24 hours. The primary outcome variable of interest for this study was the presence of SSI within 30 days of autologous breast reconstruction. Cohort characteristics and 30-day outcomes were compared using χ² and Fischer exact tests for categorical variables and Student t tests for continuous variables. Multivariate logistic regression was used to control for confounders. RESULTS: A total of 1036 patients met inclusion criteria for our study. Six hundred fifty-nine patients (63.6%) received antibiotics for 24 hours postoperatively, and 377 patients (36.4%) received antibiotics for greater than 24 hours. The rate of SSI did not differ significantly between patients given antibiotics for only 24 hours and those continued on antibiotics beyond the 24-hour postoperative time period (5.01% vs 2.92%, P = 0.109). Furthermore, antibiotic duration was not predictive of SSI in multivariate regression modeling. CONCLUSIONS: We did not find a statistically significant difference in the rate of SSI in patients who received 24 hours of postoperative antibiotics compared to those that received antibiotics for greater than 24 hours. These findings held for both purely autologous reconstruction as well as latissimus dorsi reconstruction in conjunction with an implant. Thus, our study does not support continuation of postoperative antibiotics beyond 24 hours after autologous breast reconstruction.

Sentinel lymph node biopsy versus axillary lymphadenectomy in patients treated with lumpectomy: an analysis of short-term outcomes.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been shown to reduce many of the long-term complications associated with a traditional axillary lymph node dissection (ALND); however, short-term outcomes have yet to be characterized. This study was designed to identify trends and differences in 30-day outcomes of partial mastectomy with concurrent SLNB or complete ALND to more effectively determine which patients may be at risk for perioperative complications. METHODS: A retrospective review of the National Surgical Quality Improvement Program database from 2010 to 2011 was performed to identify all female patients undergoing partial mastectomy with concurrent ALND or SLNB. Logistic regression analysis was used to investigate the relationship between surgical management of the axilla and 30-day complications and readmissions. RESULTS: Of the 6,841 patients identified, 1,877 (27.4 %) received a complete ALND. Overall, the ALND cohort demonstrated significantly more readmissions and reoperations, as well as longer operative times and fewer outpatient procedures. No difference was detected in postoperative complications between the two groups. However, after adjusting for potential confounders, ALND did not predict increased risk of 30-day morbidity or unplanned 30-day readmission compared with SLNB in patients undergoing partial mastectomy. CONCLUSIONS: After adjusting for potential confounders, ALND does not significantly increase the risk of 30-day postoperative overall morbidity or readmission compared with SLNB. Improvement of postoperative outcomes should focus on management of high-risk patients and perioperative complications regardless of surgical management of the axilla.

Skin-sparing mastectomy and immediate tissue expander breast reconstruction in patients with macromastia using the Passot breast reduction pattern.

Skin-sparing mastectomy (SSM) with immediate tissue expander reconstruction poses a challenge in the patient with macromastia or excessive ptosis. Skin reduction via the Wise pattern has been described but is associated with high rates of skin necrosis. The study group consisted of 43 women with grade 2 or 3 ptosis who underwent SSM and immediate reconstruction with tissue expanders, using the Passot (horizontal) skin reduction pattern. Age ranged from 31 to 67 years (mean, 51 years). The endpoints measured were time to final expansion, mastectomy skin flap necrosis, infectious complications, and total complications. Thirty reconstructions were bilateral and 13 were unilateral (73 breasts total). Follow-up ranged from 6 to 55 months (mean, 20). Common comorbid conditions included hypertension (n = 16), obesity (n = 22), and smoking (n = 9). The mean body mass index was 30.6 (range, 19.4-58.6). Twenty-one patients underwent chemotherapy; 12 received radiation. The mean initial fill was 196 mL (range, 0-420 mL), and the mean time to final expansion was 84 days (range, 28-225 days). Five patients did not complete the reconstruction, 2 because of cancer recurrence and 3 because of infection. There were 3 cases of mastectomy flap necrosis occurring after tissue expander placement (7%). There were 7 infectious complications (16%). The use of a horizontal breast reduction pattern at the time of expander placement produces consistently good esthetic outcomes and a low rate of skin necrosis, and it should be considered as an option in patients with macromastia or ptosis undergoing SSM and immediate reconstruction.

Risk stratification in subpectoral to prepectoral pocket conversion to reduce post-reconstruction animation deformity.

BACKGROUND: Animation deformity is a morbid complication that impacts women undergoing subpectoral implant-based breast reconstruction. Transferring implants from the subpectoral to prepectoral space, pocket conversion, can be performed to minimize this issue. While prior literature has evaluated outcomes associated with this procedure, we investigated the risk factors most commonly associated with post-conversion complications. METHODS: We performed a retrospective cohort investigation of women undergoing prepectoral pocket conversion. Pre-conversion clinical characteristics and surgical complications (major and minor) were collected. Predictors for postoperative complications were identified using univariate and multivariate logistic regression models. Odds ratios (OR) and adjusted odds ratios (aOR) are presented with 95% confidence intervals, and p-values were assessed at α = 0.05. RESULTS: A total of 34 patients (63 breasts) were included. Pocket conversion relieved animation deformity in all breasts. The overall rates of major and minor complications were 14.3% (n = 9/63) and 34.9% (n = 22/63), respectively, by mean follow-up of 11.1 months. After adjusting for confounders, pre-conversion implant rupture (OR= 6.00, CI= 0.99-34.58; aOR= 12.8, CI= 1.15-170.32) and duration of implant placement (OR=1.35, CI= 1.07-1.78; aOR= 1.1, CI= 1.00-1.21) were found to be significant predictors of major postoperative complications. CONCLUSION: With a fairly inclusive patient population, this series provides data for improved risk stratification of patients considering conversion to relieve animation deformity. Interestingly, traditional risk factors (namely, body mass index and smoking status) were not significant predictors for postoperative complications, suggesting that conversion may be safe in high-risk patients. Such data support more informed preoperative counseling and wider application of this procedure.

Use of Antibiotic-impregnated Polymethylmethacrylate (PMMA) Plates for Prevention of Periprosthetic Infection in Breast Reconstruction.

Periprosthetic infections remain a major challenge for breast reconstruction. Local antibiotic delivery systems, such as antibiotic beads and spacers, have been widely used within other surgical fields, but their use within plastic surgery remains scarce. In this study, we demonstrate the use of antibiotic-impregnated polymethylmethacrylate (PMMA) plates for infection prophylaxis in tissue expander (TE)-based breast reconstruction. Methods: A retrospective review of patients who underwent immediate breast reconstruction with prepectoral TEs over the span of 5 years performed by two surgeons was completed, revealing a total of 447 patients. Data pertaining to patient demographics, operative details, and postoperative outcomes were recorded. Fifty patients underwent TE reconstruction with the addition of a PMMA plate (Stryker, Kalamazoo, Michigan) impregnated with tobramycin and vancomycin. Antibiotic plates were removed at the time of TE-to-implant exchange. Patient-matching analysis was performed using the 397 patients without PMMA plates to generate a 50-patient nonintervention cohort for statistical analysis. Results: The intervention cohort (n = 50) and 1:1 patient-matched nonintervention cohort (n = 50) demonstrated no statistically significant differences in patient demographics or operative characteristics other than PMMA plate placement. The rate of operative periprosthetic infection was 4% in the intervention group and 14% in the nonintervention group (P = 0.047). The rate of TE explantation was also reduced in the intervention group (6% versus 18%; P = 0.036). Follow-up averaged 9.1 and 8.9 months for the intervention and nonintervention groups, respectively (P = 0.255). Conclusion: Local antibiotic delivery using antibiotic-impregnated PMMA plates can be safely and effectively used for infection prevention with TE-based breast reconstruction.

Does Higher Intraoperative Fraction of Inspired Oxygen Improve Complication Rates Following Implant-Based Breast Reconstruction?

Background: The surgical literature debates about whether an average intraoperative fractional inspired level of oxygen (FiO2) greater than 80% confers lower postsurgical complication rates. Although some evidence demonstrates minimal or no difference in short-term mortality or surgical site infections, few studies suggest negative long-term outcomes. Objectives: To the best of our knowledge, this is the first study examining the relationship between intraoperative FiO2 levels and postoperative outcomes in the setting of immediate prepectoral implant-based breast reconstruction. Methods: The authors retrospectively reviewed the complication profiles of 309 patients who underwent prepectoral 2-stage breast reconstruction following mastectomy between 2018 and 2021 at a single institution. Two cohorts were created based on whether intraoperative FiO2 was greater than 80% or less than or equal to 80%. Complication rates between the cohorts were analyzed using Chi-squared test, Fisher's exact test, and multivariable logistic regressions. Variables examined included demographic information; smoking history; preexisting comorbidities; history of chemotherapy, radiation, or axillary lymph node dissection; and perioperative information. Results: Chi-squared and multivariable regression analysis demonstrated no significant difference between cohorts in complication rates other than reoperation. Reoperation rates were significantly increased in the FiO2 greater than 80% cohort (P = 0.018). Multivariable logistic regression also demonstrated that the use of acellular dermal matrix was significantly associated with increased postoperative complications (odds ratio 11.985; P = 0.034). Conclusions: Complication rates did not statistically differ in patients with varying intraoperative FiO2 levels outside of reoperation rates. In the setting of implant-based prepectoral breast reconstruction, hyperoxygenation likely does not lead to improved postsurgical outcomes.

Securin and B-cyclin/CDK are the only essential targets of the APC.

The anaphase-promoting complex/cyclosome (APC) is a highly conserved ubiquitin ligase that controls passage through the cell cycle by targeting many proteins for proteolysis. The complex is composed of at least thirteen core subunits, eight of which are essential, and two activating subunits, Cdc20 (essential) and Cdh1/Hct1 (non-essential). Previously, it was not known which APC targets are sufficient to explain the essential nature of the complex. Here, we show that each of the eight normally essential APC subunits is rendered non-essential ('bypass-suppressed') by the simultaneous removal/inhibition of the APC substrates securin (Pds1) and B-type cyclin/CDK (Clb/CDK). In strains lacking the APC, levels of Clb2 and Clb3 remain constant, but Clb/CDK activity oscillates as cells cycle. This suggests that in the absence of B-type cyclin destruction, oscillation of the Clb/CDK-inhibitor Sic1 is sufficient to trigger the feedback loops necessary for the bi-stable nature of Clb/CDK activity. These results strongly suggest that securin and B-type cyclin/CDK activity are the only obligatory targets of the APC in Saccharomyces cerevisiae.

Sensitivity of yeast strains with long G-tails to levels of telomere-bound telomerase.

The Saccharomyces cerevisiae Pif1p helicase is a negative regulator of telomere length that acts by removing telomerase from chromosome ends. The catalytic subunit of yeast telomerase, Est2p, is telomere associated throughout most of the cell cycle, with peaks of association in both G1 phase (when telomerase is not active) and late S/G2 phase (when telomerase is active). The G1 association of Est2p requires a specific interaction between Ku and telomerase RNA. In mutants lacking this interaction, telomeres were longer in the absence of Pif1p than in the presence of wild-type PIF1, indicating that endogenous Pif1p inhibits the active S/G2 form of telomerase. Pif1p abundance was cell cycle regulated, low in G1 and early S phase and peaking late in the cell cycle. Low Pif1p abundance in G1 phase was anaphase-promoting complex dependent. Thus, endogenous Pif1p is unlikely to act on G1 bound Est2p. Overexpression of Pif1p from a non-cell cycle-regulated promoter dramatically reduced viability in five strains with impaired end protection (cdc13-1, yku80Delta, yku70Delta, yku80-1, and yku80-4), all of which have longer single-strand G-tails than wild-type cells. This reduced viability was suppressed by deleting the EXO1 gene, which encodes a nuclease that acts at compromised telomeres, suggesting that the removal of telomerase by Pif1p exposed telomeres to further C-strand degradation. Consistent with this interpretation, depletion of Pif1p, which increases the amount of telomere-bound telomerase, suppressed the temperature sensitivity of yku70Delta and cdc13-1 cells. Furthermore, eliminating the pathway that recruits Est2p to telomeres in G1 phase in a cdc13-1 strain also reduced viability. These data suggest that wild-type levels of telomere-bound telomerase are critical for the viability of strains whose telomeres are already susceptible to degradation.

Successful treatment of renal amyloidosis due to familial cold autoinflammatory syndrome using an interleukin 1 receptor antagonist.

Familial cold autoinflammatory syndrome (FCAS) is an autosomal dominant disorder characterized by episodic fever, arthralgias, conjunctivitis, and rash triggered by cold exposure. FCAS is rarely associated with progressive renal insufficiency caused by renal amyloidosis. The genetic defect in patients with this disorder is caused by a mutation in the gene encoding the protein cryopyrin, leading to uninhibited activation of systemic inflammation through specific cellular signaling with increased production of a number of key cytokines, including interleukin 1. We describe the successful treatment of a patient with renal amyloidosis caused by FCAS by using a novel interleukin 1-receptor antagonist. Use of specific anticytokine therapy may be a new paradigm in the treatment of patients with renal amyloidosis caused by systemic inflammatory diseases.

The educational value of a resident aesthetic surgery clinic: a 10-year review.

BACKGROUND: Resident experience in aesthetic surgery is often deficient in many training programs around the country. OBJECTIVE: This study is the first to review the 10-year experience of a resident aesthetic clinic and identifies important educational aspects necessary for residency training in aesthetic surgery. METHODS: The operative experience of each chief resident from 1994 through 2004 and the database of the resident aesthetic surgery clinic during the same period were reviewed. A questionnaire was also distributed to all past chief residents regarding their experience with the clinic. RESULTS: Over 1600 new patients were evaluated in the resident aesthetic clinic in the last 10 years, with 482 patients undergoing 805 procedures. Each chief resident performed 104.5 +/- 25.1 (mean +/- SD) procedures as a primary surgeon. The resident clinic contributed 82.4% of the total aesthetic surgery procedures, as recorded by the chief residents' Accreditation Council for Graduate Medical Education operative logs. For the last 10 years, the reoperative complication rate was 3.1%, and no litigation has been brought against any resident or attending surgeon. CONCLUSIONS: Our resident aesthetic surgery clinic emphasizes an intensive exposure to aesthetic surgery with the opportunity to gain "hands-on" operative experience, while reducing the liability for the attending surgeon. The means to obtain adequate resident education in aesthetic surgery and ways to improve such an experience are also discussed.

Cycling without the cyclosome: modeling a yeast strain lacking the APC.

The construction of viable Saccharomyces cerevisiae strains that lack the anaphase promoting complex (APC) was recently reported. The normally lethal deletions of APC genes were suppressed by the double deletion of the PDS1 and CLB5 genes in conjunction with the insertion of multiple copies of the SIC1 gene controlled by its endogenous promoter. It was proposed that cyclic expression and degradation of Sic1 results in oscillations of Clb/CDK activity necessary for the cell cycle. We have used an updated version of a mathematical model of the yeast cell cycle to model strains that lack the APC. With a few modifications, the model accurately simulates the viability of Apc- strains, as well as the phenotypes of 27 other previously characterized strains. We discuss a few minor inconsistencies between the model and experiment, and how these may inform future revisions to the model.

Two partially embedded rings resulting in chronic erosion of a finger.

Embedded rings in the fingers may cause neurovascular, tendinous, or bony injury. These are very rare injuries usually found in patients with mental illness. To minimize the potentially serious complications, mentally-challenged individuals should have tight rings removed. We present a case of a 41-year-old gentleman with schizophrenia who had two partially embedded rings on his left index finger but consistently refused to have the rings removed. Following appointment of a guardian, the patient was returned for surgery to remove the rings. He recovered without further sequelae.

The effect of saliva and oral intake on the tensile properties of sutures: an experimental study.

The plastic surgeon often operates in the oral cavity. Little or no information exists regarding the effect of saliva and oral intake upon the tensile properties of suture. Polyglactin 910 (Vicryl) and chromic gut were studied. Five sutures of each type were subjected to saline, saliva, milk, or soy milk over different durations of exposure. Suture breaking strength was tested. A 4-way interaction between suture type, size, liquid, and time was significant (P = 0.0046). Sutures soaked in saliva were significantly weaker. No significant difference was observed between sutures soaked in milk or soy. Saliva appears to enhance degradation rates in both sutures. Suture selection in the oral cavity should be predicated upon the demands of the repair and surgeon's preference. Postoperative feeding instructions should limit tension across mucosal repairs, but the selection of formula should be based upon nutritional requirements and preferences of the child rather than concern over suture degradation.

Squamous cell carcinoma arising from an arteriovenous malformation of the scalp.

We present the case of a 70-year-old man with a congenital scalp lesion consistent with an arteriovenous malformation (AVM) which over the last 3 years had developed ulcerative changes and bleeding in the central aspect that was a biopsy proven squamous cell carcinoma (SCCA). To control hemorrhage during surgery, a radiologist performed selective embolization of major feeding arteries in the lesion three days before the surgery. After total resection of the lesion, a scalp reconstruction was performed by using a free latissimus muscle flap and skin graft. As a result, bleeding was well controlled, the AVM and SCCA were totally resected, and satisfactory aesthetic results were obtained. This appears to be the first description of a SCCA arising from a chronic AVM. This is suggestive of a possible Marjolin's ulcer from a chronic wound bed.

Precise destruction: an emerging picture of the APC.

Cell cycle transitions are often accompanied by the degradation of regulatory molecules. Targeting proteins to the proteasome for degradation is accomplished by the covalent addition of ubiquitin chains. The specificity of this pathway is largely dictated by a set of enzymes called ubiquitin ligases (or E3s). The anaphase-promoting complex (or APC) is a ubiquitin ligase that has a particularly prominent role in regulating cell cycle progression. To date, the APC is the most complicated member of the RING/cullin family of multisubunit E3s. It includes at least 13 core subunits and three related adaptors. A combination of biochemical, genetic, and structural approaches are now shedding light on the enzymology of the APC. This review will focus on these data, drawing parallels with related ubiquitin ligases.

Breast reduction as an alternative treatment option for early breast cancer in women with macromastia.

Macromastia has been considered a relative contraindication to breast conservation therapy because of difficulties with postoperative radiation therapy and cosmesis. This study evaluates the feasibility of the inferior pedicle reduction mammaplasty as a component of breast conservation therapy for patients with early breast cancer. A retrospective review identified 6 patients with macromastia receiving oncologic treatment of breast cancer and simultaneous breast reduction. Mean age was 43.5 +/- 8.7 (mean +/- SD) years, and all breast cancers were stage I or II, averaging 2.3 +/- 1.5 cm in size. All patients underwent a Wise-pattern inferior pedicle breast reduction after cancer extirpation and received postoperative radiation as part of their treatment. They were evaluated for postoperative complications, esthetic outcome of the breasts, and local recurrence. Patients in this series were followed for an average of 30.3 months, with no significant postoperative complications and recurrences. Breast reduction incisions healed primarily and adjuvant radiation was completed without a delay. All patients were pleased with the esthetic result and had improvement of their symptoms related to macromastia. Thus, we believe that breast reduction is a reasonable and safe option for early breast cancer patients with macromastia who desire breast conservation therapy. Our combined oncologic and reconstructive approach may improve the outcome of this group of patients with early breast cancers.

An architectural map of the anaphase-promoting complex.

The anaphase-promoting complex or cyclosome (APC) is an unusually complicated ubiquitin ligase, composed of 13 core subunits and either of two loosely associated regulatory subunits, Cdc20 and Cdh1. We analyzed the architecture of the APC using a recently constructed budding yeast strain that is viable in the absence of normally essential APC subunits. We found that the largest subunit, Apc1, serves as a scaffold that associates independently with two separable subcomplexes, one that contains Apc2 (Cullin), Apc11 (RING), and Doc1/Apc10, and another that contains the three TPR subunits (Cdc27, Cdc16, and Cdc23). We found that the three TPR subunits display a sequential binding dependency, with Cdc27 the most peripheral, Cdc23 the most internal, and Cdc16 between. Apc4, Apc5, Cdc23, and Apc1 associate interdependently, such that loss of any one subunit greatly reduces binding between the remaining three. Intriguingly, the cullin and TPR subunits both contribute to the binding of Cdh1 to the APC. Enzymatic assays performed with APC purified from strains lacking each of the essential subunits revealed that only cdc27Delta complexes retain detectable activity in the presence of Cdh1. This residual activity depends on the C-box domain of Cdh1, but not on the C-terminal IR domain, suggesting that the C-box mediates a productive interaction with an APC subunit other than Cdc27. We have also found that the IR domain of Cdc20 is dispensable for viability, suggesting that Cdc20 can activate the APC through another domain. We have provided an updated model for the subunit architecture of the APC.