A systematic review of randomised controlled trials in breast reconstruction.

BACKGROUND: For preference sensitive treatments, such as breast reconstructions, there are barriers to conducting randomised controlled trials (RCTs). The primary aims of this systematic review were to investigate what type of research questions are explored by RCTs in breast reconstruction, where have they been performed and where have they been published, and to thematise the research questions and thus create an overview of the state of the research field. METHODS: Randomised controlled trials investigating any aspect of breast reconstructions were included. The PubMed database was searched with a pre-defined search string. Inclusion and data abstraction was performed in a pre-defined standardised fashion. For the purpose of this study, we defined key issues as comparison of categories of breast reconstruction and comparison of immediate and delayed breast reconstruction, when the thematisation was done. RESULTS: A total of 419 abstracts were retrieved from the search. Of the 419, 310 were excluded as they were not RCTs concerning some aspect of breast reconstruction, which left us with 110 abstracts to be included in the study. The research questions of the included studies could more or less be divided into seven different themes inclusive of 2 key issues: Other issues - comparison of different categories of breast reconstruction, comparison of immediate and delayed breast reconstruction, surgical details within a category of breast reconstruction, surgical details valid for several categories of breast reconstruction, donor site management, anaesthetics, and non-surgical details. Only five studies compared key issues, and they all illustrate the challenges with RCTs in breast reconstruction. CONCLUSIONS: A total of 110 publications based on RCTs in breast reconstruction have been published. Seven themes of research questions could be identified. Only five studies have explored the key issues. Better scientific evidence is needed for the key issues in breast reconstruction, for example by implementing a new study design in the field.

Recurrence of Atrial Fibrillation in Patients With New-Onset Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting.

Importance: New-onset postoperative atrial fibrillation (POAF) occurs in approximately 30% of patients undergoing coronary artery bypass grafting (CABG). It is unknown whether early recurrence is associated with worse outcomes. Objective: To test the hypothesis that early AF recurrence in patients with POAF after CABG is associated with worse outcomes. Design, Setting, and Participants: This Swedish nationwide cohort study used prospectively collected data from the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry and 3 other mandatory national registries. The study included patients who underwent isolated first-time CABG between January 1, 2007, and December 31, 2020, and developed POAF. Data analysis was performed between March 6 and September 16, 2023. Exposure: Early AF recurrence defined as an episode of AF leading to hospital care within 3 months after discharge. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes included ischemic stroke, any thromboembolism, heart failure hospitalization, and major bleeding within 2 years after discharge. The groups were compared with multivariable Cox regression models, with early AF recurrence as a time-dependent covariate. The hypothesis tested was formulated after data collection. Results: Of the 35 329 patients identified, 10 609 (30.0%) developed POAF after CABG and were included in this study. Their median age was 71 (IQR, 66-76) years. The median follow-up was 7.1 (IQR, 2.9-9.0) years, and most patients (81.6%) were men. Early AF recurrence occurred in 6.7% of patients. Event rates (95% CIs) per 100 patient-years with vs without early AF recurrence were 2.21 (1.49-3.24) vs 2.03 (1.83-2.25) for all-cause mortality, 3.94 (2.92-5.28) vs 2.79 (2.56-3.05) for heart failure hospitalization, and 3.97 (2.95-5.30) vs 2.74 (2.51-2.99) for major bleeding. No association between early AF recurrence and all-cause mortality was observed (adjusted hazard ratio [AHR], 1.17 [95% CI, 0.80-1.74]; P = .41). In exploratory analyses, there was an association with heart failure hospitalization (AHR, 1.80 [95% CI, 1.32-2.45]; P = .001) and major bleeding (AHR, 1.92 [1.42-2.61]; P < .001). Conclusions and Relevance: In this cohort study of early AF recurrence after POAF in patients who underwent CABG, no association was found between early AF recurrence and all-cause mortality. Exploratory analyses showed associations between AF recurrence and heart failure hospitalization, oral anticoagulation, and major bleeding.

Women's decision process when actively choosing to 'go flat' after breast cancer: a constructivist grounded theory study.

OBJECTIVE: This study aims to describe a conceptual model that could illuminate the decision process women go through when choosing to go flat on one or both sides due to breast cancer. METHODS: A qualitative design, with constructivist grounded theory was used. Eighteen women were individually interviewed, digitally or by telephone, until saturation was reached. Data were analysed using a constant comparative iterative method in accordance with grounded theory. By examining the text data to identify the decision process for going flat and rejecting reconstructive surgery open coding was obtained. As the study proceeded patterns were explored and categories developed into a core category. RESULTS: The overall decision process for women choosing to go flat on one or both sides emerged in three phases: Phase 1, where the women are forced to "Face the cancer", Phase 2 comprising "Reflections on health and motivation" and Phase 3, described as "Hobson's choice". The fundament of the decision process was found in the core category "Establishing and safeguarding the chosen self". CONCLUSIONS: The decision process involved in actively going flat and rejecting reconstructive surgery is founded in the individual woman's motivations, such as view of femininity and apprehensions about the offered reconstructive surgery.

National long-term patient-reported outcomes following mastectomy with or without breast reconstruction: The Swedish Breast Reconstruction Outcome Study Part 2 (SweBRO 2).

BACKGROUND: The Swedish Breast Reconstruction Outcome Study (SweBRO) initiative is a nationwide study with the primary aim of assessing long-term outcomes after mastectomy with and without breast reconstruction (BR). The current part (SweBRO 2) is designed to evaluate health-related quality of life (HRQoL), with the hypothesis that BR has a positive impact on patient-reported HRQoL in the long-term. METHODS: Women who underwent mastectomy in Sweden in 2000, 2005, or 2010 and were alive at the time of the survey were identified through the National Breast Cancer Registry. Eligible participants received formal invitation letters to take part in a survey evaluating their HRQoL at 5 , 10, or 15 years post-mastectomy. The EORTC QLQ-C30, EORTC QLQ-BR23, and EQ-5D-3L questionnaires were employed. RESULTS: Of 2904 respondents (50% of 5853 invited), 895 (31%) had received BR. Among them, 516 (58%) were reconstructed with implants and 281 (31%) with autologous tissue. Women with BR scored significantly better in the EORCT QLQ-C30 physical functioning domain (mean 90 versus 81 points), fatigue (mean 21 versus 25), and dyspnoea (mean 16 versus 22) compared to non-reconstructed women. The EORTC QLQ-BR23 revealed that women with BR experienced favourable sexual functioning compared with non-reconstructed women (mean 26 versus 14). The EQ-5D-3L visual analogue scale score was similar between groups. CONCLUSION: The current study underscores the benefits of BR for long-term well-being, for example, in terms of physical and sexual functioning. These underline the importance of informing women undergoing mastectomy about BR alternatives and its potential benefits in enhancing long-term well-being.

Systematic review of cost-effectiveness in breast reconstruction: deep inferior epigastric perforator flap vs. implant-based breast reconstruction.

BACKGROUND: There are several techniques for reconstructing breasts after mastectomy, but little scientific evidence for which technique is superior. The aim of this systematic review was to compare the cost-effectiveness of implant-based and autologous reconstruction and to evaluate the overall certainty of evidence, as well as the quality of reporting of the included studies. METHODS: Studies investigating the cost-effectiveness of breast reconstruction with a deep inferior epigastric perforator (DIEP) flap compared to implant-based reconstruction, meeting criteria defined in a PICO (population, intervention, comparison, and outcome), were included. Medline, PubMed, Embase, Cochrane library, CinahL, EconLit, and NHS EED databases were searched. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence, and the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) 2022 was used to evaluate the quality of reporting. RESULTS AND CONCLUSIONS: A total of 256 abstracts were retrieved from the search, and after scrutiny, seven studies were included. The findings of this present systematic review should be interpreted with caution as the overall certainty of evidence is low (GRADE ƟƟОО). The included studies suggest that DIEP-flaps are cost-effective compared with implant-based breast reconstruction when the applied cost-effectiveness thresholds of $50,000 to $100,000 per quality-adjusted life years are used. It is noteworthy that no high level evidence exists regarding cost-effeciency, to support recommendations and decision in breast reconstruction. Methodological issues that can be improved in future studies are presented.

Statin treatment after surgical aortic valve replacement for aortic stenosis is associated with better long-term outcome.

OBJECTIVES: The aim of this study was to evaluate the association between statin use after surgical aortic valve replacement for aortic stenosis and long-term risk for major adverse cardiovascular events (MACEs) in a large population-based, nationwide cohort. METHODS: All patients who underwent isolated surgical aortic valve replacement due to aortic stenosis in Sweden 2006-2020 and survived 6 months after discharge were included. Individual patient data from 5 nationwide registries were merged. Primary outcome is MACE (defined as all-cause mortality, myocardial infarction or stroke). Multivariable Cox regression model adjusted for age, sex, comorbidities, valve type, operation year and secondary prevention medications is used to evaluate the association between time-updated dispense of statins and long-term outcome in the entire study population and in subgroups based on age, sex and comorbidities. RESULTS: A total of 11 894 patients were included. Statins were dispensed to 49.8% (5918/11894) of patients at baseline, and 51.0% (874/1713) after 10 years. At baseline, 3.6% of patients were dispensed low dose, 69.4% medium dose and 27.0% high-dose statins. After adjustments, ongoing statin treatment was associated with a reduced risk for MACE [adjusted hazard ratio 0.77 (95% confidence interval 0.71-0.83). P < 0.001], mainly driven by a reduction in all-cause mortality [adjusted hazard ratio, 0.70 (0.64-0.76)], P < 0.001. The results were consistent in all subgroups. CONCLUSIONS: The results suggest that statin therapy might be beneficial for patients undergoing surgical aortic valve replacement for aortic stenosis. Randomized controlled trials are warranted to establish causality between statin treatment and improved outcome.

Renin-angiotensin system inhibition after surgical aortic valve replacement for aortic stenosis.

OBJECTIVE: The optimal medical therapy after surgical aortic valve replacement (SAVR) for aortic stenosis remains unknown. Renin-angiotensin system (RAS) inhibitors could potentially improve cardiac remodelling and clinical outcomes after SAVR. METHODS: All patients undergoing SAVR due to aortic stenosis in Sweden 2006-2020 and surviving 6 months after surgery were included. The primary outcome was major adverse cardiovascular events (MACEs; all-cause mortality, stroke or myocardial infarction). Secondary endpoints included the individual components of MACE and cardiovascular mortality. Time-updated adjusted Cox regression models were used to compare patients with and without RAS inhibitors. Subgroup analyses were performed, as well as a comparison between angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). RESULTS: A total of 11 894 patients (mean age, 69.5 years, 40.4% women) were included. Median follow-up time was 5.4 (2.7-8.5) years. At baseline, 53.6% of patients were dispensed RAS inhibitors, this proportion remained stable during follow-up. RAS inhibition was associated with a lower risk of MACE (adjusted hazard ratio (aHR) 0.87 (95% CI 0.81 to 0.93), p<0.001), mainly driven by a lower risk of all-cause death (aHR 0.79 (0.73 to 0.86), p<0.001). The lower MACE risk was consistent in all subgroups except for those with mechanical prostheses (aHR 1.07 (0.84 to 1.37), p for interaction=0.040). Both treatment with ACE inhibitors (aHR 0.89 (95% CI 0.82 to 0.97)) and ARBs (0.87 (0.81 to 0.93)) were associated with lower risk of MACE. CONCLUSION: The results of this study suggest that medical therapy with an RAS inhibitor after SAVR is associated with a 13% lower risk of MACE and a 21% lower risk of all-cause death.

Long-term patient-reported back and shoulder function after delayed breast reconstruction with a latissimus dorsi flap: case-control cohort study.

BACKGROUND: Sacrifice of the latissimus dorsi (LD) muscle might entail donor site morbidity when used in delayed breast reconstruction. Previous studies are small, have short follow-up, and demonstrate diverging results. The aims of this study were to evaluate long-term patient-reported effects on shoulder and back function following LD flap harvest, and to investigate predictors for a worse outcome. METHOD: This is a retrospective observational case-control cohort study. Cases were all patients who had undergone an LD flap reconstruction during the years 2007-2017. Controls were patients reconstructed with a deep inferior epigastric perforator (DIEP) flap during the same time period. Participants completed two validated questionnaires; the BREAST-Q reconstruction LD domains and the Western Ontario Shoulder Osteoarthritis Index (WOOS). RESULTS: A total of 135 cases (75 per cent) and 118 controls (60 per cent) responded to the questionnaires. The mean follow-up time was 7 years. Patients reconstructed with a LD flap were significantly less satisfied with their back and shoulder function when compared to the DIEP controls, as measured with BREAST-Q and WOOS. Predictors for a poor patient-reported back and shoulder function included axillary surgery and axillary radiotherapy, especially when combined, as well as higher age at reconstruction. CONCLUSION: Patients who have undergone LD flap for delayed breast reconstruction had a lower satisfaction with back and shoulder function, when compared to patients who had undergone a DIEP reconstruction. Delayed LD reconstruction should be used with care, especially in patients who have undergone axillary surgery and axillary radiotherapy.

Postdischarge major bleeding, myocardial infarction, and mortality risk after coronary artery bypass grafting.

OBJECTIVE: To investigate the incidence and mortality risk associated with postdischarge major bleeding after coronary artery bypass grafting (CABG), and relate this to the incidence of, and mortality risk from, postdischarge myocardial infarction. METHODS: All patients undergoing first-time isolated CABG in Sweden in 2006-2017 and surviving 14 days after hospital discharge were included in a cohort study. Individual patient data from the SWEDEHEART Registry and five other mandatory nationwide registries were merged. Piecewise Cox proportional hazards models were used to investigate associations between major bleeding, defined as hospitalisation for bleeding, with subsequent mortality risk. Similar Cox proportional hazards models were used to investigate the association between postdischarge myocardial infarction and mortality risk. RESULTS: Among 36 633 patients, 2429 (6.6%) had a major bleeding event and 2231 (6.1%) had a myocardial infarction. Median follow-up was 6.0 (range 0-11) years. Major bleeding was associated with higher mortality risk <30 days (adjusted HR (aHR)=20.2 (95% CI 17.3 to 23.5)), 30-365 days (aHR=3.8 (95% CI 3.4 to 4.3)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. Myocardial infarction was associated with higher mortality risk <30 days (aHR=20.0 (95% CI 16.7 to 23.8)), 30-365 days (aHR=4.1 (95% CI 3.6 to 4.8)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. CONCLUSIONS: The increase in mortality risk associated with a postdischarge major bleeding after CABG is substantial and is similar to the mortality risk associated with a postdischarge myocardial infarction.

A systematic review of the scientific evidence of venous supercharging in autologous breast reconstruction with abdominally based flaps.

BACKGROUND: Abdominally based free flaps are commonly used in breast reconstruction. A frequent complication is venous congestion, which might contribute to around 40% of flap failures. One way to deal with it is venous supercharging. The primary aim of this study was to investigate the scientific evidence for the effects of venous supercharging. METHODS: A systematic literature search was conducted in PubMed, CINAHL, Embase, and Cochrane library. The included articles were critically appraised, and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: Thirty-six studies were included. Most studies had serious study limitations and problems with directness. Three studies report 'routine' use of venous supercharging and performed it prophylactically in patients who did not have clinical signs of venous congestion. Seventeen studies report on flap complications, of which one is a randomised controlled trial demonstrating statistically significant lower complication rates in the intervention group. The overall certainty of evidence for the effect of a venous supercharging on flap complications, length of hospital stay and operative time, in patients without clinical signs of venous congestion, is very low (GRADE ⊕ ⊕ ⊝ ⊝), and low on and surgical takebacks (GRADE ⊕ ⊕ ⊝ ⊝). Twenty-one studies presented data on strategies and overall certainty of evidence for using radiological findings, preoperative measurements, and clinical risk factors to make decisions on venous supercharging is very low (GRADE ⊕ ⊝ ⊝ ⊝). CONCLUSION: There is little scientific evidence for how to predict in which cases, without clinical signs of venous congestion, venous supercharging should be performed. The complication rate might be lower in patients in which a prophylactic venous anastomosis has been performed. TRIAL REGISTRATION: PROSPERO (CRD42022353591).

Normative BREAST-Q reconstruction scores for satisfaction and well-being of the breasts and potential donor sites: what are Swedish women of the general population satisfied/dissatisfied with?

BACKGROUND: Normative data for interpreting the BREAST-Q reconstruction module are currently limited to four populations. The primary aim of this study was to create Swedish normative values for the BREAST-Q reconstruction domains. The secondary aim was to describe what aspects of the breasts and potential donor sites that women of the general population are generally satisfied or dissatisfied with. METHODS: The BREAST-Q reconstruction module was sent to a random sample of 400 women currently living in Region Västra Götaland. Descriptive data are presented. RESULTS: One hundred and forty-six women answered the questionnaire (36.5%). The mean age of the cohort was 53 years, and the mean body mass index (BMI) was 25 kg/m2. Mean total scores ranged from 50 to 90. The mean score for satisfaction with breast was 57 on a 0-100 scale. Women with high BMI values seem to be less satisfied with their breasts and physical and sexual well-being. The participants were most satisfied with their breasts when clothed. Overall, the reported physical well-being related to potential donor sites was high. CONCLUSIONS: Normative data for BREAST-Q constitute a reference point, which allows us to put another perspective on changes in scores rather than just comparing scores before and after surgery. Scores were somewhat different than scores in previously published normative populations, which indicates that there might be cultural differences in breast satisfaction.

Prevalence of women with breast implants in Sweden: a study based on the population-based mammography screening programme.

BACKGROUND: Knowledge about the prevalence of women with breast implants is paramount in calculations of risks and in estimations of effects on screening and breast cancer treatment. Most of the estimations of prevalence made to date are rough and often based on sales data. The main aim of this study was to  calculate the prevalence of breast implants in Swedish women. The secondary aim was to investigate if it is feasible to establish the occurrence of breast implants with the help of the public mammography screening programme, in a country with a publicly funded welfare-type healthcare system and with a clear documentation of screening. METHODS: Information on implants was prospectively collected from all screening attendants from 1st of February 2022 to 1st of August 2022 based on a question from the radiographer to the woman and later verified on the mammogram. RESULTS: During the study period 4,639 women were screened, of which 182 had implants (3.9%). The  frequency varies between 1.6 and 6.4% in different age groups. CONCLUSION: The prevalence of breast implants in Swedish women is estimated to be around 4%. The population-based mammography screening programme in countries with a publicly funded welfare-type healthcare system and a clear documentation of mammography screening attendance, seems to be a feasible way to establish the prevalence of breast implants in the population. The large number of women with breast implants warrants further studies regarding the best diagnostic and treatment alternatives for this group. Pre-registration: ClinicalTrials.Gov identifier NCT05222100.

Comparison of patient-reported achievements of goals and core outcomes with delayed breast reconstruction in irradiated patients: latissimus dorsi with an implant versus DIEP.

BACKGROUND: Different women's individual goals with a breast reconstruction vary, and few studies compare techniques in light of the different goals. This study aimed to compare patient-reported core outcomes in patients reconstructed with deep inferior epigastric artery perforator (DIEP) flaps and latissimus dorsi (LD) flaps. Second, breast-related factors that the patients were particularly satisfied/dissatisfied with were analyzed. METHODS: This was a retrospective cross-sectional study, which includes women who had undergone mastectomy and radiation, followed by delayed breast reconstructions with either LD flap and implant or DIEP flap during 2007-2017. The patient-reported core outcomes of overall breast-specific quality of life, normality, women's cosmetic satisfaction, self-esteem, emotional well-being, and physical well-being were analyzed using BREAST-Q. RESULTS: The patients were divided into LD and implant (n = 135 patients) and DIEP (n = 118 patients) groups, and both were demographically similar. The median follow-up was 8 years. The DIEP group scored significantly higher than the LD and implant group in five out of six domains. A high satisfaction was reported in questions regarding the feeling or appearance when having clothes on, whereas the greatest dissatisfaction was reported regarding questions entailing symmetry and the appearance without clothes. CONCLUSION: After 7 years, patients' breast-specific quality of life, normality, women's cosmetic satisfaction, self-esteem, emotional well-being, and physical well-being seem to be higher in irradiated patients who have been reconstructed with DIEP flap as compared to patients reconstructed with LD flap and implant. In both groups, patient satisfaction is high regarding their appearance when clothed, whereas the lowest satisfaction scores were reported in situations without clothing.

The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

Medical therapy after surgical aortic valve replacement for aortic regurgitation.

OBJECTIVES: Current clinical guidelines have no specific recommendations regarding medical therapy after surgical aortic valve replacement in patients with aortic regurgitation (AR). We studied the association between medical therapy with renin-angiotensin system (RAS) inhibitors, statins and ß-blockers and long-term major adverse cardiovascular events. METHODS: All patients undergoing valve replacement due to AR between 2006 and 2017 in Sweden and alive 6 months after discharge were included. Time-dependent multivariable Cox regression models adjusted for age, sex, patient characteristics, comorbidities, other medications and year of surgical aortic valve replacement were used. Primary outcome was a composite of all-cause mortality, myocardial infarction and stroke. Subgroup analyses based on age, sex, heart failure, low ejection fraction, hyperlipidaemia and hypertension were performed. RESULTS: A total of 2204 patients were included [median follow-up 5.0 years (range 0.0-11.5)]. At baseline, 68% of the patients were dispensed RAS inhibitors, 80% ß-blockers and 35% statins. Dispense of RAS inhibitors and ß-blockers declined over time, especially during the first year after baseline, while dispense of statins remained stable. Treatment with RAS inhibitors or statins was associated with a reduced risk of the primary outcome [adjusted hazard ratio (aHR) 0.71, 95% confidence interval (CI) 0.57-0.87 and aHR 0.78, 95% CI 0.62-0.99, respectively]. The results were consistent in subgroups based on age, sex and comorbidities. ß-Blocker treatment was associated with an increased risk for the primary outcome (aHR 1.35, 95% CI 1.07-1.70). CONCLUSIONS: The results indicate a potential beneficial association of RAS inhibitors and statins as part of a secondary preventive treatment regime after aortic valve replacement in patients with AR. The role of ß-blockers needs to be further investigated.

Rituximab pharmacokinetic and pharmacokinetic-pharmacodynamic evaluation based on a study in diffuse large B-cell lymphoma: Influence of tumor size on pharmacokinetic and assessment of pharmacokinetic similarity.

Dr. Reddy's Laboratories rituximab (DRL_RI; Dr. Reddy's Laboratories SA, Basel, Switzerland) is under development as a rituximab biosimilar. Study RI-01-002 (Clinical Trials Registry - India/2012/11/003129), comparing DRL_RI to the reference medicinal product (RMP) MabThera® (Roche, Grenzach-Wyhlen, Germany), demonstrated pharmacokinetic (PK) equivalence and showed comparable pharmacodynamic, efficacy, safety, and immunogenicity profiles. We used data from the same study to perform population PK and PK-pharmacodynamic analyses: first exploring possible factors influencing the PK similarity assessment between products and then performing simulations to investigate the impact of tumor size on rituximab PK. Nonlinear mixed-effects models for PK, tumor size, tumor size-PK, and tumor response were developed independently. The final PK model included drug product as a dose-scaling parameter and predicted a 6.75% higher dose reaching the system in RMP-treated patients. However, when tumor size was included in the tumor size-PK model, the drug product effect was no longer observed. The model rather indicated that patients with larger tumor size have higher clearance. Further simulations confirmed that higher baseline tumor size is associated to slightly lower rituximab exposure. Tumor response, described by a continuous-time Markov model, did not differ between drug products. Both had higher effects during the first 20 weeks of treatment. Also, the model described a subpopulation of nonresponders to treatment (42%) with faster transitions to a worse state. The different rituximab exposure initially detected between drug products (6.75%) was shown using PK/PK-pharmacodynamic analysis to be attributed to a tumor size imbalance between treatment groups. PK/PK-pharmacodynamic analyses may contribute to PK similarity assessments.

Donor-Site Satisfaction of DIEP and Latissimus Dorsi Flaps-A Comparative Cohort Study.

BACKGROUND: Understanding of donor-site morbidity and satisfaction after breast reconstruction is limited. There are few previous studies comparing satisfaction with different donor sites in breast reconstruction. This study aimed to examine the long-term patient-reported satisfaction with the donor site of latissimus dorsi (LD) flaps in comparison to the deep inferior epigastric artery perforator (DIEP) flaps. Further, a systematic review of previously published studies was conducted. METHODS: In this retrospective cross-sectional study, all women who underwent breast reconstructions with either LD or DIEP flap following mastectomy and radiotherapy between 2007 and 2017 were included; patient-reported satisfaction was assessed using the BREAST-Q reconstruction module. For the systematic review, studies examining patient-reported abdominal satisfaction and well-being, and meeting the PICO (Population, Intervention, Comparison, and Outcome) criteria were included. RESULTS: Eligible and responding participants were divided into the LD (n = 135 patients) and DIEP (n = 118 patients) flap groups. Impairment due to muscular weakness of the donor site was more common in the LD group than that of the DIEP group. Bulging was common in the DIEP group and increased over time. Regarding the esthetic appearance of the donor site, the patients in the DIEP group were less satisfied than the LD group. The systematic review showed that most of the patients were dissatisfied with their abdomen after the operation. CONCLUSION: Patients who have undergone DIEP flap for breast reconstruction are less satisfied with the donor-site esthetics than those who have undergone LD flap. Patient-reported abdominal bulging was common in the DIEP group and the number seemed to increase over time. Most patients were not satisfied with their abdominal scarring postoperatively, as per the systematic review. These results may indicate a need for more nuanced preoperative patient information, as well as improvements in the surgical management of the donor site, for DIEP flap reconstructions.

Type A Aortic Dissection Repair in Patients With Prior Cardiac Surgery.

BACKGROUND: Emergency surgery for acute type A aortic dissection in patients with previous cardiac surgery is controversial. This study aimed to evaluate the association between previous cardiac surgery and outcomes after surgery for acute type A aortic dissection, to appreciate whether emergency surgery can be offered with acceptable risks. METHODS: All patients operated on for acute type A aortic dissection between 2005 and 2014 from the Nordic Consortium for Acute Type A Aortic Dissection database were eligible. Patients with previous cardiac surgery were compared with patients without previous cardiac surgery. Univariable and multivariable statistical analyses were performed to identify predictors of 30-day mortality and early major adverse events (a secondary composite endpoint comprising 30-day mortality, perioperative stroke, postoperative cardiac arrest, or de novo dialysis). RESULTS: In all, 1159 patients were included, 40 (3.5%) with previous cardiac surgery. Patients with previous cardiac surgery had higher 30-day mortality (30% vs 17.8%, P = .049), worse medium-term survival (51.7% vs 71.2% at 5 years, log rank P = .020), and higher unadjusted prevalence of major adverse events (52.5% vs 35.7%, P = .030). In multivariable analysis, previous cardiac surgery was not associated with 30-day mortality (odds ratio 0.78; 95% CI, 0.30-2.07; P = .624) or major adverse events (odds ratio 1.07; 95% CI, 0.45-2.55, P = .879). CONCLUSIONS: Major adverse events after surgery for acute type A aortic dissection were more frequent in patients with previous cardiac surgery. Previous cardiac surgery itself was not an independent predictor for adverse events, although the small sample size precludes definite conclusions. Previous cardiac surgery should not deter from emergency surgery.

Patient experience of implant loss after immediate breast reconstruction: An interpretative phenomenological analysis.

Immediate breast reconstruction (IBR) is an integral part of modern breast cancer treatment. Our aim was to investigate patient experience with implant loss after IBR by using interpretative phenomenological analysis (IPA). We conducted semi-structured interviews with eight informants. We analyzed data according to the IPA flexible seven-stage process and four main themes were developed: immediate breast reconstruction as the indisputable choice, a difficult experience, an altered body: redefining normality, and trying to cope. The experience of implant loss appears to affect women for many years and might overshadow some of the benefits of IBR.

Agreement of clinical assessment of burn size and burn depth between referring hospitals and burn centres: A systematic review.

BACKGROUND: The quality of burn care is highly dependent on the initial assessment and care. The aim of this systematic review was to investigate the agreement of clinical assessment of burn depth and %TBSA between the referring units and the receiving burn centres. METHODS: Included articles had to meet criteria defined in a PICO (patients, interventions, comparisons, outcomes). Relevant databases were searched using a predetermined search string (November 6th 2021). Data were extracted in a standardised fashion. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for test accuracy was used to assess the certainty of evidence. The QUADAS-2 tool was used to assess the risk of bias of individual studies as 'high', 'low' or 'unclear'. RESULTS: A total of 412 abstracts were retrieved and of these 28 studies with a total of 6461 patients were included, all reporting %TBSA and one burn depth. All studies were cross-sectional and most of them comprising retrospectively enrolled consecutive cohort. All studies showed a low agreement between %TBSA calculations made at referring units and at burn centres. Most studies directly comparing estimations of %TBSA at referring institutions and burn centers showed a proportion of overestimations of 50% or higher. The study of burn depth showed that 55% were equal to the estimates from the burn centre. Most studies had severe study limitations and the risk of imprecision was high. The overall certainty of evidence for accuracy of clinical estimations in referring centres is low (GRADE ⊕⊕ОО) for %TBSA and very low (GRADE ⊕ООО) for burn depth and resuscitation. CONCLUSION: Overestimation of %TBSA at referring hospitals occurs very frequently. The overall certainty of evidence for accuracy of clinical estimations in referring centres is low for burn size and very low for burn depth. The findings suggest that the burn community has a significant challenge in educating and communicating better with our colleagues at referring institutions and that high-quality studies are needed.