Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor.

BACKGROUND: Inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9)-low density lipoprotein receptor interaction with injectable monoclonal antibodies or small interfering RNA lowers plasma low density lipoprotein-cholesterol, but despite nearly 2 decades of effort, an oral inhibitor of PCSK9 is not available. Macrocyclic peptides represent a novel approach to target proteins traditionally considered intractable to small-molecule drug design. METHODS: Novel mRNA display screening technology was used to identify lead chemical matter, which was then optimized by applying structure-based drug design enabled by novel synthetic chemistry to identify macrocyclic peptide (MK-0616) with exquisite potency and selectivity for PCSK9. Following completion of nonclinical safety studies, MK-0616 was administered to healthy adult participants in a single rising-dose Phase 1 clinical trial designed to evaluate its safety, pharmacokinetics, and pharmacodynamics. In a multiple-dose trial in participants taking statins, MK-0616 was administered once daily for 14 days to characterize the safety, pharmacokinetics, and pharmacodynamics (change in low density lipoprotein cholesterol). RESULTS: MK-0616 displayed high affinity (Ki = 5pM) for PCSK9 in vitro and sufficient safety and oral bioavailability preclinically to enable advancement into the clinic. In Phase 1 clinical studies in healthy adults, single oral doses of MK-0616 were associated with >93% geometric mean reduction (95% CI, 84-103) of free, unbound plasma PCSK9; in participants on statin therapy, multiple-oral-dose regimens provided a maximum 61% geometric mean reduction (95% CI, 43-85) in low density lipoprotein cholesterol from baseline after 14 days of once-daily dosing of 20 mg MK-0616. CONCLUSIONS: This work validates the use of mRNA display technology for identification of novel oral therapeutic agents, exemplified by the identification of an oral PCSK9 inhibitor, which has the potential to be a highly effective cholesterol lowering therapy for patients in need.

Maryland's Global Budget Revenue Payment Model and Shifts in the Surgical Site of Care Among Medicare Beneficiaries.

OBJECTIVE: To assess the association between the Global Budget Revenue (GBR) payment model and shifts to the outpatient setting for surgical procedures among Medicare fee-for-service beneficiaries in Maryland versus control states. SUMMARY BACKGROUND DATA: The GBR model provides fixed global payments to hospitals to reduce spending growth and incentivize hospitals to reduce the costs of care while improving care quality. Since surgical care is a major contributor to hospital spending, the GBR model might accelerate the ongoing shift from the inpatient to the outpatient setting to generate additional savings. METHODS: A difference-in-differences (DiD) design was used to compare changes in surgical care settings over time from pre-GBR (2011-2013) to post-GBR (2014-2018) for Maryland versus control states for common surgeries that could be performed in the outpatient setting. A cross-sectional approach was used to compare the difference in care settings in 2018 for total knee arthroplasty which was on Medicare's Inpatient-Only List before then. RESULTS: We studied 47,542 surgical procedures from 44,410 beneficiaries in Maryland and control states. GBR's 2014 implementation was associated with an acceleration in the shift from inpatient to outpatient settings for surgical procedures in Maryland (DiD: 3.9 percentage points, 95% CI: 2.3, 5.4). Among patients undergoing total knee arthroplasty in 2018, the proportion of outpatient surgeries in Maryland was substantially higher than that in control states (difference: 27.6 percentage points, 95% CI: 25.6, 29.6). CONCLUSIONS: Implementing Maryland's GBR payment model was associated with an acceleration in the shift from inpatient to outpatient hospital settings for surgical procedures.

The Role of AI in Drug Discovery.

The emergence of Artificial Intelligence (AI) in drug discovery marks a pivotal shift in pharmaceutical research, blending sophisticated computational techniques with conventional scientific exploration to break through enduring obstacles. This review paper elucidates the multifaceted applications of AI across various stages of drug development, highlighting significant advancements and methodologies. It delves into AI's instrumental role in drug design, polypharmacology, chemical synthesis, drug repurposing, and the prediction of drug properties such as toxicity, bioactivity, and physicochemical characteristics. Despite AI's promising advancements, the paper also addresses the challenges and limitations encountered in the field, including data quality, generalizability, computational demands, and ethical considerations. By offering a comprehensive overview of AI's role in drug discovery, this paper underscores the technology's potential to significantly enhance drug development, while also acknowledging the hurdles that must be overcome to fully realize its benefits.

Frail but Resilient: Frailty in Autologous Breast Reconstruction is Associated with Worse Surgical Outcomes but Equivalent Long-Term Patient-Reported Outcomes.

BACKGROUND: Frailty is associated with higher risk of complications following breast reconstruction, but its impact on long-term surgical and patient-reported outcomes has not been investigated. We examined the association of the five-item modified frailty index (MFI) score with long-term surgical and patient-reported outcomes in autologous breast reconstruction. PATIENTS AND METHODS: We conducted a retrospective cohort study of consecutive patients who underwent mastectomy and autologous breast reconstruction between January 2016 and April 2022. Primary outcome was any flap-related complication. Secondary outcomes were patient-reported outcomes and predictors of complications in the frail cohort. RESULTS: We identified 1640 reconstructions (mean follow-up 24.2 ± 19.2 months). In patients with MFI ≥ 2, the odds of surgical [odds ratio (OR) 2.13, p = 0.023] and medical (OR 17.02, p < 0.001) complications were higher than in nonfrail patients. We found no significant difference in satisfaction with the breast (p = 0.287), psychosocial well-being (p = 0.119), or sexual well-being (p = 0.314) according to MFI score. Chronic obstructive pulmonary disease was an independent predictor of infection (OR 3.70, p = 0.002). Tobacco use (OR 7.13, p = 0.002) and contralateral prophylactic mastectomy (OR 2.36, p = 0.014) were independent predictors of wound dehiscence. Dependent functional status (OR 2.36, p = 0.007) and immediate reconstruction (compared with delayed reconstruction; OR 3.16, p = 0.026) were independent predictors of skin flap necrosis. Dependent functional status was also independently associated with higher odds of reoperation (OR 2.64, p = 0.011). CONCLUSION: Frailty is associated with higher risk of complications in breast reconstruction, but there is no significant difference in long-term patient-reported outcomes. MFI should be considered in breast reconstruction to improve outcomes in high-risk frail patients.

A Multi-institutional Analysis of a Textbook Outcome Among Patients Undergoing Microvascular Breast Reconstruction.

BACKGROUND: Individual outcomes may not accurately reflect the quality of perioperative care. Textbook outcomes (TOs) are composite metrics that provide a comprehensive evaluation of hospital performance and surgical quality. This study aimed to investigate the prevalence and predictors of TOs in a multi-institutional cohort of patients who underwent breast reconstruction with deep inferior epigastric artery perforator flaps. METHODS: For autologous reconstruction, a TO was previously defined as a procedure without intraoperative complications, reoperation, infection requiring intravenous antibiotics, readmission, mortality, systemic complications, operative duration ≤12 hours for bilateral and ≤10 hours for unilateral/stacked reconstruction, and length of stay (LOS) ≤5 days. We investigated associations between patient-level factors and achieving a TO using multivariable regression analysis. RESULTS: Of 1000 patients, most (73.2%) met a TO. The most common reasons for deviation from a TO were reoperation (9.6%), prolonged operative time (9.5%), and prolonged LOS (9.2%). On univariate analysis, tobacco use, obesity, widowed/divorced marital status, and contralateral prophylactic mastectomy or bilateral reconstruction were associated with a lower likelihood of TOs (P < 0.05). After adjustment, bilateral prophylactic mastectomy (odds ratio [OR], 5.71; P = 0.029) and hormonal therapy (OR, 1.53; P = 0.050) were associated with a higher likelihood of TOs; higher body mass index (OR, 0.91; P = <0.001) was associated with a lower likelihood. CONCLUSION: Approximately 30% of patients did not achieve a TO, and the likelihood of achieving a TO was influenced by patient and procedural factors. Future studies should investigate how this metric may be used to evaluate patient and hospital-level performance to improve the quality of care in reconstructive surgery.

Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives.

A new ibuprofen derivative, (E)-2-(4-isobutylphenyl)-N'-(4-oxopentan-2-ylidene) propane hydrazide (IA), was synthesized, along with its metal complexes with Co, Cu, Ni, Gd, and Sm, to investigate their anti-inflammatory efficacy and COX-2 inhibition potential. Comprehensive characterization, including 1H NMR, MS, FTIR, UV-vis spectroscopy, and DFT analysis, were employed to determine the structural configurations, revealing unique motifs for Gd/Sm (capped square antiprismatic/tricapped trigonal prismatic) and Cu/Ni/Co (octahedral) complexes. Molecular docking with the COX-2 enzyme (PDB code: 5IKT) and pharmacokinetic assessments through SwissADME indicated that these compounds have superior binding energies and pharmacokinetic profiles, including BBB permeability and gastrointestinal absorption, compared to the traditional ibuprofen standalone. Their significantly lower IC50 values further suggest a higher efficacy as anti-inflammatory agents and COX-2 inhibitors. These research findings not only introduce promising ibuprofen derivatives for therapeutic applications but also set the stage for future validation and exploration of this new generation of ibuprofen compounds.

Development and Assessment of Machine Learning Models for Individualized Risk Assessment of Mastectomy Skin Flap Necrosis.

OBJECTIVE: To develop, validate, and evaluate ML algorithms for predicting MSFN. BACKGROUND: MSFN is a devastating complication that causes significant distress to patients and physicians by prolonging recovery time, compromising surgical outcomes, and delaying adjuvant therapy. METHODS: We conducted comprehensive review of all consecutive patients who underwent mastectomy and immediate implant-based reconstruction from January 2018 to December 2019. Nine supervised ML algorithms were developed to predict MSFN. Patient data were partitioned into training (80%) and testing (20%) sets. RESULTS: We identified 694 mastectomies with immediate implant-based reconstruction in 481 patients. The patients had a mean age of 50 ± 11.5 years, years, a mean body mass index of 26.7 ± 4.8 kg/m 2 , and a median follow-up time of 16.1 (range, 11.9-23.2) months. MSFN developed in 6% (n = 40) of patients. The random forest model demonstrated the best discriminatory performance (area under curve, 0.70), achieved a mean accuracy of 89% (95% confidence interval, 83-94), and identified 10 predictors of MSFN. Decision curve analysis demonstrated that ML models have a superior net benefit regardless of the probability threshold. Higher body mass index, older age, hypertension, subpectoral device placement, nipple-sparing mastectomy, axillary nodal dissection, and no acellular dermal matrix use were all independently associated with a higher risk of MSFN. CONCLUSIONS: ML algorithms trained on readily available perioperative clinical data can accurately predict the occurrence of MSFN and aid in individualized patient counseling, preoperative optimization, and surgical planning to reduce the risk of this devastating complication.

Association between patient-surgeon race and gender concordance and patient-reported outcomes following breast cancer surgery.

PURPOSE: Surgeon- and patient-related factors have been shown to influence patient experiences, quality of life (QoL), and surgical outcomes. We examined the association between patient-surgeon race and gender concordance with QoL after breast reconstruction. METHODS: We conducted a retrospective cross-sectional analysis of patients who underwent lumpectomy or mastectomy followed by breast reconstruction over a 3-year period. We created the following categories with respect to the race and gender of a patient-surgeon triad: no, intermediate, and perfect concordance. Multivariable regression was used to correlate postoperative global (SF-12) and condition-specific (BREAST-Q) QoL performance with patient-level covariates, gender and race concordance. RESULTS: We identified 375 patients with a mean (± SD) age of 57.6 ± 11.9 years, median (IQR) body mass index of 27.5 (24.0, 32.0), and median morbidity burden of 3 (2, 4). The majority of encounters were of intermediate concordance for gender (70%) and race (52%). Compared with gender-discordant triads, intermediate gender concordance was associated with higher SF-Mental scores (ß, 2.60; 95% CI, 0.21-4.99, p = 0.003). Perfect race concordance (35% of encounters) was associated with significantly higher adjusted SF-Physical scores (ß, 2.14; 95% CI, 0.50-4.22, p = 0.045) than the race-discordant group. There were no significant associations observed between race or gender concordance and BREAST-Q performance. CONCLUSION: Race-concordant relationships following breast cancer surgery were more likely to have improved global QoL. Perfect gender concordance was not associated with variation in QoL outcomes. Policy-level interventions are needed to facilitate personalized care and optimize breast cancer surgery outcomes.

The Use of Machine Learning for Predicting Complications of Free-Flap Head and Neck Reconstruction.

BACKGROUND: Machine learning has been increasingly used for surgical outcome prediction, yet applications in head and neck reconstruction are not well-described. In this study, we developed and evaluated the performance of ML algorithms in predicting postoperative complications in head and neck free-flap reconstruction. METHODS: We conducted a comprehensive review of patients who underwent microvascular head and neck reconstruction between January 2005 and December 2018. Data were used to develop and evaluate nine supervised ML algorithms in predicting overall complications, major recipient-site complication, and total flap loss. RESULTS: We identified 4000 patients who met inclusion criteria. Overall, 33.7% of patients experienced a complication, 26.5% experienced a major recipient-site complication, and 1.7% suffered total flap loss. The k-nearest neighbors algorithm demonstrated the best overall performance for predicting any complication (AUROC = 0.61, sensitivity = 0.60). Regularized regression had the best performance for predicting major recipient-site complications (AUROC = 0.68, sensitivity = 0.66), and decision trees were the best predictors of total flap loss (AUROC = 0.66, sensitivity = 0.50). CONCLUSIONS: ML accurately identified patients at risk of experiencing postsurgical complications, including total flap loss. Predictions from ML models may provide insight in the perioperative setting and facilitate shared decision making.

Area Deprivation Index is Associated with Variation in Quality of Life and Psychosocial Well-being Following Breast Cancer Surgery.

BACKGROUND: Neighborhood-level factors have been shown to influence surgical outcomes through material deprivation, psychosocial mechanisms, health behaviors, and access to resources. To date, no study has examined the relationship between area-level deprivation (ADI) and post-mastectomy outcomes. METHODS: A cross-sectional survey of adult female breast cancer patients who underwent lumpectomy or mastectomy between January 2018 to June 2019 was carried out. Patient-specific characteristics and ADI information were abstracted and correlated with postoperative global- (SF-12) and condition-specific (BREAST-Q) quality-of-life performance via multivariable regression. Patients were classified into three ADI terciles: 0-39 (low deprivation), 40-59 (moderate deprivation), and 60-100 (high deprivation). RESULTS: A total of 564 consecutive patients were identified, being mostly white (75%) with mean age of 60.2 ± 12.4 years, median body mass index of 27.8 [interquartile range (IQR) 24.3-32.2) kg/m2, median Charlson Comorbidity Index of 3 (IQR 2-5), and mean ADI of 42.3 ± 25.7. African American and Hispanic patients and those with high BMI were more likely to reside in highly deprived neighborhoods (p = 0.003 and p < 0.001). In adjusted models, patients in highly deprived neighborhoods had significantly lower mean SF-12 physical (44.9 [95% CI, 43.8-46.0] versus 44.9 [95% CI, 43.7-46.1] versus 46.3 [95% CI, 45.3-47.3], p = 0.03) and BREAST-Q psychosocial well-being scores (63.5 [95% CI, 59.32-67.8] versus 69.3 [95% CI, 65.1-73.6] versus 69.7 [95% CI, 66.4-73.1], p = 0.01) relative to moderate- and low-deprivation groups. CONCLUSIONS: Patients residing in the most deprived neighborhoods were identified to have worse psychological well-being and quality-of-life. The ADI should be incorporated into the shared decision-making process and perioperative counseling to engender value-based and personalized care, especially for vulnerable populations.

Outcomes of Complex Abdominal Wall Reconstruction After Oncologic Resection: 14-Year Experience at an NCI-Designated Cancer Center.

BACKGROUND: Outcomes studies for abdominal wall reconstruction (AWR) in the setting of previous oncologic extirpation are lacking. We sought to evaluate long-term outcomes of AWR using acellular dermal matrix (ADM) after extirpative resection, compare them to primary herniorrhaphy, and report the rates and predictors of postoperative complications. METHODS: We conducted a retrospective cohort study of patients who underwent AWR after oncologic resection from March 2005 to June 2019 at a tertiary cancer center. The primary outcome was hernia recurrence (HR). Secondary outcomes included surgical site occurrences (SSOs), surgical site infection (SSIs), length of hospital stay (LOS), reoperation, and 30-day readmission. RESULTS: Of 720 consecutive patients who underwent AWR during the study period, 194 (26.9%) underwent AWR following resection of abdominal wall tumors. In adjusted analyses, patients who had AWR after extirpative resection were more likely to have longer LOS (ß, 2.57; 95%CI, 1.27 to 3.86, p < 0.001) than those with primary herniorrhaphy, but the risk of HR, SSO, SSI, 30-day readmission, and reoperation did not differ significantly. In the extirpative cohort, obesity (Hazard ratio, 6.48; p = 0.003), and bridged repair (Hazard ratio, 3.50; p = 0.004) were predictors of HR. Radiotherapy (OR, 2.23; p = 0.017) and diabetes mellites (OR, 3.70; p = 0.005) were predictors of SSOs. Defect width (OR, 2.30; p < 0.001) and mesh length (OR, 3.32; p = 0.046) were predictors of SSIs. Concomitant intra-abdominal surgery for active disease was not associated with worse outcomes. CONCLUSIONS: AWR with ADM following extirpative resection demonstrated outcomes comparable with primary herniorrhaphy. Preoperative risk assessment and optimization are imperative for improving outcomes.

Long-term Surgical and Patient-Reported Outcomes Comparing Skin-Preserving, Staged Versus Delayed Microvascular Breast Reconstruction.

BACKGROUND: Skin-preserving, staged, microvascular, breast reconstruction often is preferred in patients requiring postmastectomy radiotherapy (PMRT) but may lead to complications. We compared the long-term surgical and patient-reported outcomes between skin-preserving and delayed microvascular breast reconstruction with and without PMRT. METHODS: We conducted a retrospective, cohort study of consecutive patients who underwent mastectomy and microvascular breast reconstruction between January 2016 and April 2022. The primary outcome was any flap-related complication. The secondary outcomes were patient-reported outcomes and tissue-expander complications. RESULTS: We identified 1002 reconstructions (672 delayed; 330 skin-preserving) in 812 patients. Mean follow-up was 24.2 ± 19.3 months. PMRT was required in 564 reconstructions (56.3%). In the non-PMRT group, skin-preserving reconstruction was independently associated with shorter hospital stay (ß - 0.32, p = 0.045) and lower odds of 30-days readmission (odds ratio [OR] 0.44, p = 0.042), seroma (OR 0.42, p = 0.036), and hematoma (OR 0.24, p = 0.011) compared with delayed reconstruction. In the PMRT group, skin-preserving reconstruction was independently associated with shorter hospital stay (ß - 1.15, p < 0.001) and operative time (ß - 97.0, p < 0.001) and lower odds of 30-days readmission (OR 0.29, p = 0.005) and infection (OR 0.33, p = 0.023) compared with delayed reconstruction. Skin-preserving reconstruction had a 10.6% tissue expander loss rate and did not differ from delayed reconstruction in terms of patient-reported satisfaction with breast, psychosocial well-being, or sexual well-being. CONCLUSIONS: Skin-preserving, staged, microvascular, breast reconstruction is safe regardless of the need for PMRT, with an acceptable tissue expander loss rate, and is associated with improved flap outcomes and similar patient-reported quality of life to that of delayed reconstruction.

Outcomes of Complex Abdominal Wall Reconstruction with Biologic Mesh in Patients with 8 Years of Follow-Up.

BACKGROUND: While many studies evaluated outcomes of abdominal wall reconstruction with biologic mesh, long-term data is lacking. In this study, we sought to analyze the outcomes of complex AWR with biologic mesh in a robust cohort of patients with a mean follow up of 8 years. METHODS: We conducted a longitudinal study of AWR patients from 2005 to 2019. Hernia recurrence was the primary outcome, and surgical site occurrence was the secondary outcome. Predictive/protective factors were identified using a Cox proportional hazards regression models. RESULTS: We identified 109 consecutive patients who met the inclusion criteria. Patient's mean (± SD) age was 57.5 ± 11.8 years, mean body mass index was 30.7 ± 7.2 kg/m2, and mean follow-up time was 96.2 ± 15.9 months. Fifty-six percent had clean defects, 34% had clean-contaminated defects, and 10% had contaminated/infected defects. Patients had a mean defect size of 261 ± 199.6 cm2 and mean mesh size of 391.3 ± 160.2 cm2. Nineteen patients (17.4%) developed HR at the final follow-up date. Obesity was independently associated with a four-fold higher risk of HR (hazard ratio, 3.98; 95%CI, 1.34 to 14.60, p = 0.02). SSOs were identified in 24.8% of patients. A prior hernia repair was associated with a three-fold higher risk of SSOs (Odds ratio, 3.13; 95%CI, 1.10 to 8.94, p = 0.03). No patient developed mesh infection. CONCLUSION: These longitudinal data demonstrate that complex AWR with biologic mesh provides long-term durable outcomes with acceptable HR and SSO rates despite high contamination levels, patients complexity, and large defect size.

Brownian motion of soft particles near a fluctuating lipid bilayer.

The dynamics of a soft particle suspended in a viscous fluid can be changed by the presence of an elastic boundary. Understanding the mechanisms and dynamics of soft-soft surface interactions can provide valuable insights into many important research fields, including biomedical engineering, soft robotics development, and materials science. This work investigates the anomalous transport properties of a soft nanoparticle near a visco-elastic interface, where the particle consists of a polymer assembly in the form of a micelle and the interface is represented by a lipid bilayer membrane. Mesoscopic simulations using a dissipative particle dynamics model are performed to examine the impact of micelle's proximity to the membrane on its Brownian motion. Two different sizes are considered, which correspond to ≈10-20nm in physical units. The wavelengths typically seen by the largest micelle fall within the range of wavenumbers where the Helfrich model captures fairly well the bilayer mechanical properties. Several independent simulations allowed us to compute the micelle trajectories during an observation time smaller than the diffusive time scale (whose order of magnitude is similar to the membrane relaxation time of the largest wavelengths), this time scale being hardly accessible by experiments. From the probability density function of the micelle normal position with respect to the membrane, it is observed that the position remains close to the starting position during ≈0.05τd (where τd corresponds to the diffusion time), which allowed us to compare the negative excess of mean-square displacement (MSD) to existing theories. In that time range, the MSD exhibits different behaviors along parallel and perpendicular directions. When the micelle is sufficiently close to the bilayer (its initial distance from the bilayer equals approximately twice its gyration radius), the micelle motion becomes quickly subdiffusive in the normal direction. Moreover, the temporal evolution of the micelle MSD excess in the perpendicular direction follows that of a nanoparticle near an elastic membrane. However, in the parallel direction, the MSD excess is rather similar to that of a nanoparticle near a liquid interface.

Sugar Beet Root Storage Properties Are Unaffected by Cercospora Leaf Spot.

Cercospora leaf spot (CLS; causal agent Cercospora beticola Sacc.) is endemic in many sugar beet production regions due to the widespread distribution of C. beticola and the inability of current management practices to provide complete control of the disease. Roots harvested from plants with CLS, therefore, are inevitably incorporated into sugar beet root storage piles, even though the effects of CLS on root storage properties are largely unknown. Research was conducted to determine the effects of CLS on storage properties including root respiration rate, sucrose loss, invert sugar accumulation, loss in recoverable sucrose yield, and changes in sucrose loss to molasses with respect to CLS disease severity and storage duration. Roots were obtained from plants with four levels of CLS severity in each of three production years, stored at 5°C and 95% relative humidity for up to 120 days, and evaluated for storage characteristics after 30, 90, and 120 days storage. No significant or repeatable effects of CLS on root respiration rate, sucrose loss, invert sugar accumulation, loss in recoverable sucrose yield, or change in sucrose loss to molasses were detected after 30, 90, or 120 days storage regardless of the severity of CLS disease symptoms. Therefore, no evidence was found that CLS accelerates sugar beet storage losses, and it is concluded that roots harvested from plants with CLS can be stored without additional or specialized precaution, regardless of CLS symptom severity.

Functional Muscle Transfer after Oncologic Extremity Resection.

BACKGROUND: Functional muscle transfer (FMT) can provide wound closure and restore adequate muscle function for patients with oncologic extremity defects. Herein we describe our institutional experience with FMT after oncological resection and provide a systematic review and meta-analysis of the available literature on this uncommon procedure. METHODS: A single-institution retrospective review was performed, including all patients who received FMT after oncological resection from 2005 to 2021. For the systematic review and meta-analysis, PubMed, Cochrane, Medline, and Embase libraries were queried according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines; results were pooled, weighted by study size, and analyzed. RESULTS: The meta-analysis consisted of seven studies with 70 patients overall, demonstrating a mean Medical Research Council (MRC) score of 3.78 (95% confidence interval: 2.97-4.56; p < 0.01). The systematic review included 28 studies with 103 patients. Receipt of adjuvant chemotherapy was associated with significantly lower mean MRC score (3.00 ± 1.35 vs. 3.90 ± 1.36; p = 0.019). Seventy-four percent of the patients underwent free FMT, with the most common donor muscle being the latissimus dorsi (55%). The flap loss rate was 0.8%. Neoadjuvant chemotherapy (p = 0.03), radiotherapy (p = 0.05), pedicled FMTs (p = 0.01), and a recipient femoral nerve (p = 0.02) were associated with significantly higher complication rates. The institutional retrospective review identified 13 patients who underwent FMT after oncological resection with a median follow-up time of 21 months (range: 6-74 months). The most common tumor necessitating FMT was undifferentiated pleomorphic sarcoma (77%), and the most common donor muscle was the latissimus dorsi (62%). A high body mass index was associated with prolonged neuromuscular recovery (R = 0.87, p = 0.002). CONCLUSION: FMT after oncological resection may contribute to improved extremity function. Careful consideration of risk factors and preoperative planning is imperative for successful FMT outcomes.

Impact of Obesity on Outcomes of Prepectoral vs Subpectoral Implant-Based Breast Reconstruction.

BACKGROUND: The impact of obesity on outcomes of prepectoral vs subpectoral implant-based reconstruction (IBR) is not well-established. OBJECTIVES: The goal of this study was to assess the surgical and patient-reported outcomes of prepectoral vs subpectoral IBR. The authors hypothesized that obese patients would have similar outcomes regardless of device plane. METHODS: We conducted a retrospective review of obese patients who underwent 2-stage IBR from January 2017 to December 2019. The primary endpoint was the occurrence of any breast-related complication; the secondary endpoint was device explantation. RESULTS: The authors identified a total of 284 reconstructions (184 prepectoral, 100 subpectoral) in 209 patients. Subpectoral reconstruction demonstrated higher rates of overall complications (50% vs 37%, P = .047) and device explantation (25% vs 12.5%, P = .008) than prepectoral reconstruction. In multivariable regression, subpectoral reconstruction was associated with higher risk of infection (hazard ratio [HR], 1.65; P = .022) and device explantation (HR, 1.97; P = .034). Subgroup analyses demonstrated significantly higher rates of complications and explantation in the subpectoral group in those with a body mass index (BMI) ≥ 35 and BMI ≥40. The authors found no significant differences in mean scores for satisfaction with the breast (41.57 ± 13.19 vs 45.50 ± 11.91, P = .469), psychosocial well-being (39.43 ± 11.23 vs 39.30 ± 12.49, P = .915), and sexual well-being (17.17 ± 7.83 vs 17.0 ± 9.03, P = .931) between subpectoral and prepectoral reconstruction. CONCLUSIONS: Prepectoral reconstruction was associated with significantly decreased overall complications, infections, and device explantation in obese patients compared with subpectoral reconstruction. Prepectoral reconstruction provides superior outcomes to subpectoral reconstruction with comparable patient-reported outcomes.

The Skin Necrosis Conundrum: Examining Long-term Outcomes and Risk Factors in Implant-Based Breast Reconstruction.

BACKGROUND: Mastectomy skin flap necrosis (MSFN) is a common complication following mastectomy that causes significant distress to patients and physicians and also compromises oncologic, surgical, and quality-of-life outcomes. OBJECTIVES: We sought to investigate the long-term outcomes of MSFN following implant-based reconstruction (IBR) and determine the rates and predictors of post-MSFN complications. METHODS: This was a 20-year analysis of consecutive adult (>18 years) patients who developed MSFN following mastectomy and IBR from January 2001 to January 2021. Multivariable analyses were performed to identify factors associated with post-MSFN complications. RESULTS: We identified 148 reconstructions, with a mean follow-up time of 86.6 ± 52.9 months. The mean time from reconstruction to MSFN was 13.3 ± 10.4 days, and most cases (n = 84, 56.8%) were full-thickness injuries. Most cases (63.5%) were severe, 14.9% were moderate, and 21.6% were mild. Forty-six percent (n = 68) developed a breast-related complication, with infection being the most common (24%). An independent predictor of overall complications was longer time from reconstruction to MSFN (odds ratio [OR], 1.66; P = .040). Aging was an independent predictor of overall complications (OR, 1.86; P = .038); infection (OR, 1.72; P = .005); and dehiscence (OR, 6.18; P = .037). Independent predictors of dehiscence were longer interval from reconstruction to MSFN (OR, 3.23; P = .018) and larger expander/implant size (OR, 1.49; P = .024). Independent predictors of explantation were larger expander/implant size (OR, 1.20; P = .006) and nipple-sparing mastectomy (OR, 5.61; P = .005). CONCLUSIONS: MSFN is associated with high risk of complications following IBR. Awareness of the timing and severity of MSFN and the predictors of post-MSFN complications is crucial for guiding evidence-based decision-making and improving outcomes.

Effectiveness of a fluid immersion simulation system in the acute post-operative management of pressure ulcers: A prospective, randomised controlled trial.

The fluid immersion simulation system (FIS) has demonstrated good clinical applicability. This is the first study to compare surgical flap closure outcomes of FIS with an air-fluidised bed (AFB), considered as standard of care. The success of closure after 14 days post-op was the primary endpoint. Secondary endpoints were incidences of complications in the first 2 weeks after surgery and the rate of acceptability of the device. Thirty-eight subjects were in the FIS group while 42 subjects were placed in the AFB group. Flap failure rate was similar between groups (14% vs. 12%; p = 0.84). Complications, notably dehiscence and maceration, were significantly higher in the FIS group (40% vs. 17%; p = 0.0296). The addition of a microclimate regulation device (ClimateCare®) to FIS for the last 43 patients showed a significant decrease in the rate of flap failure (71% vs. 16%; p = 0.001) and incidence of complications (33% vs. 0%; p = 0.011). There was no statistically significant difference between the FIS and air-fluidised bed (AFB) in the rate of acceptability (nurse acceptance: 1.49 vs. 1.72; p = 0.8; patient acceptance: 2.08 vs. 2.06; p = 0.17), which further illustrates the potential implementation of this tool in a patient-care setting. Our results show that the use of ClimateCare® in combination with FIS can be a better alternative to the AFB in surgical closure of pressure ulcers.

Determinants of telemedicine adoption among financially distressed patients with cancer during the COVID-19 pandemic: insights from a nationwide study.

PURPOSE: Telemedicine use during the COVID-19 pandemic among financially distressed patients with cancer, with respect to the determinants of adoption and patterns of utilization, has yet to be delineated. We sought to systematically characterize telemedicine utilization in financially distressed patients with cancer during the COVID-19 pandemic. METHODS: We conducted a cross-sectional analysis of nationwide survey data assessing telemedicine use in patients with cancer during the COVID-19 pandemic collected by Patient Advocate Foundation (PAF) in December 2020. Patients were characterized as financially distressed by self-reporting limited financial resources to manage out-of-pocket costs, psychological distress, and/or adaptive coping behaviors. Primary study outcome was telemedicine utilization during the pandemic. Secondary outcomes were telemedicine utilization volume and modality preferences. Multivariable and Poisson regression analyses were used to identify factors associated with telemedicine use. RESULTS: A convenience sample of 627 patients with cancer responded to the PAF survey. Telemedicine adoption during the pandemic was reported by 67% of patients, with most (63%) preferring video visits. Younger age (19-35 age compared to ≥ 75 age) (OR, 6.07; 95% CI, 1.47-25.1) and more comorbidities (≥ 3 comorbidities compared to cancer only) (OR, 1.79; 95% CI, 1.13-2.65) were factors associated with telemedicine adoption. Younger age (19-35 years) (incidence rate ratios [IRR], 1.78; 95% CI, 24-115%) and higher comorbidities (≥ 3) (IRR; 1.36; 95% CI, 20-55%) were factors associated with higher utilization volume. As area deprivation index increased by 10 units, the number of visits decreased by 3% (IRR 1.03, 95% CI, 1.03-1.05). CONCLUSIONS: The rapid adoption of telemedicine may exacerbate existing inequities, particularly among vulnerable financially distressed patients with cancer. Policy-level interventions are needed for the equitable and efficient provision of this service.