Invasive electrochemical impedance spectroscopy with phase delay for experimental atherosclerosis phenotyping.

Distinguishing quiescent from rupture-prone atherosclerotic lesions has significant translational and clinical implications. Electrochemical impedance spectroscopy (EIS) characterizes biological tissues by assessing impedance and phase delay responses to alternating current at multiple frequencies. We evaluated invasive 6-point stretchable EIS sensors over a spectrum of experimental atherosclerosis and compared results with intravascular ultrasound (IVUS), molecular positron emission tomography (PET) imaging, and histology. Male New Zealand White rabbits (n = 16) were placed on a high-fat diet, with or without endothelial denudation via balloon injury of the infrarenal abdominal aorta. Rabbits underwent in vivo micro-PET imaging of the abdominal aorta with 68Ga-DOTATATE, 18F-NaF, and 18F-FDG, followed by invasive interrogation via IVUS and EIS. Background signal-corrected values of impedance and phase delay were determined. Abdominal aortic samples were collected for histology. Analyses were performed blindly. EIS impedance was associated with markers of plaque activity including macrophage infiltration (r = .813, p = .008) and macrophage/smooth muscle cell (SMC) ratio (r = .813, p = .026). Moreover, EIS phase delay correlated with anatomic markers of plaque burden, namely intima/media ratio (r = .883, p = .004) and %stenosis (r = .901, p = .002), similar to IVUS. 68Ga-DOTATATE correlated with intimal macrophage infiltration (r = .861, p = .003) and macrophage/SMC ratio (r = .831, p = .021), 18F-NaF with SMC infiltration (r = -.842, p = .018), and 18F-FDG correlated with macrophage/SMC ratio (r = .787, p = .036). EIS with phase delay integrates key atherosclerosis features that otherwise require multiple complementary invasive and non-invasive imaging approaches to capture. These findings indicate the potential of invasive EIS to comprehensively evaluate human coronary artery disease.

Integrative transcriptomics and cell systems analyses reveal protective pathways controlled by Igfbp-3 in anthracycline-induced cardiotoxicity.

Anthracyclines such as doxorubicin (Dox) are effective chemotherapeutic agents; however, their use is hampered by subsequent cardiotoxicity risk. Our understanding of cardiomyocyte protective pathways activated following anthracycline-induced cardiotoxicity (AIC) remains incomplete. Insulin-like growth factor binding protein (IGFBP) 3 (Igfbp-3), the most abundant IGFBP family member in the circulation, is associated with effects on the metabolism, proliferation, and survival of various cells. Whereas Igfbp-3 is induced by Dox in the heart, its role in AIC is ill-defined. We investigated molecular mechanisms as well as systems-level transcriptomic consequences of manipulating Igfbp-3 in AIC using neonatal rat ventricular myocytes and human-induced pluripotent stem cell-derived cardiomyocytes. Our findings reveal that Dox induces the nuclear enrichment of Igfbp-3 in cardiomyocytes. Furthermore, Igfbp-3 reduces DNA damage, impedes topoisomerase IIß expression (Top2ß) which forms Top2ß-Dox-DNA cleavage complex leading to DNA double-strand breaks (DSB), alleviates detyrosinated microtubule accumulation-a hallmark of increased cardiomyocyte stiffness and heart failure-and favorably affects contractility following Dox treatment. These results indicate that Igfbp-3 is induced by cardiomyocytes in an effort to mitigate AIC.

Recurrent, ICD-associated L. monocytogenes bacteraemia with multiple septic pulmonary embolisms over a 2-year period.

BACKGROUND: Listeria monocytogenes is a bacterial pathogen known for causing listeriosis, a foodborne illness with a wide spectrum of clinical presentations ranging from mild gastroenteritis to severe invasive disease, particularly affecting immunocompromised individuals, pregnant women, newborns, and the elderly. Successful treatment of patients with recurring listeria episodes due to colonised foreign material is often challenging, typically requiring a combination of antimicrobial treatment and surgical removal. CASE PRESENTATION: Here, we present a particularly complex case of chronic invasive listeriosis with a total of six relapses. After extensive investigations, the patient's ICD device was identified as the focus of infection. CONCLUSION: The confirmation of relapses through cgMLST analysis highlights the persistence of Listeria monocytogenes and the potential for recurrence even after apparent resolution of symptoms in patients with foreign material. It emphasises the necessity for a comprehensive assessment to identify and mitigate the risk of relapses, thereby ensuring optimal management and outcomes.

Patient Satisfaction Following Primary Closure or Second Intention Healing After Conventional Nasal Skin Cancer Excision: A Cross-sectional Cohort Study.

BACKGROUND: Nasal reconstruction after conventional surgical excision (CSE) of nonmelanoma skin cancer (NMSC) can be challenging. After excision and before the pathologic report, a simple reconstruction is favored. Yet, little is known about patient satisfaction after primary closure and second intention healing. OBJECTIVE: Patient satisfaction after nasal defect reconstruction with primary closure or second intention healing, using the FACE-Q Skin Cancer. METHODS: All patients who underwent CSE of nasal NMSC with immediate primary closure or second intention healing between March 2018 and March 2020 at Máxima Medisch Centrum Veldhoven were identified and asked to complete the FACE-Q Skin Cancer. RESULTS: Of 183 patients, 140 patients completed the questionnaire. Fifty-five defects were closed by primary closure (38.5%) and 88 by second intention healing (61.5%). Thirty-one complications were reported (16.7%), of which 87.1% ( n = 27) after second intention healing ( p = .004). Both groups experienced high facial and scar satisfaction, low appearance-related distress, and no to minimal adverse effects. Second intention healing had 2.7 higher odds of achieving the maximum scar satisfaction score ( p = .02). CONCLUSION: This study shows high satisfaction on facial and scar appraisal, low appearance-related distress, and no to minimal adverse effects for second intention healing and primary closure after CSE of nasal NMSC.

Local heating-induced cutaneous vasodilation in reinnervated and noninnervated deep inferior epigastric perforator flaps.

INTRODUCTION: Cutaneous vascular reactivity to local heating in free flaps has not been characterized. We aimed to assess local heating-induced cutaneous vasodilation in reinnervated and noninnervated deep inferior epigastric perforator (DIEP) flaps. METHODS: We conducted a cross-sectional study of 21 female patients with an uncomplicated unilateral delayed DIEP breast reconstruction at least 2 years after surgery. DIEP flaps and contralateral breasts were subjected to direct local heating, and skin blood flow was assessed using laser-Doppler flowmetry. To evaluate sensory-nerve-fiber function, touch perception thresholds were assessed using a 20-piece Touch-test™ Sensory Evaluator, and cutaneous warm detection and heat pain thresholds were measured using a TSA-II device. RESULTS: Of the participants, 10 had a reinnervated DIEP flap with a single coapted nerve (mean flap weight, 610 ± 296 g) and 11 had a noninnervated DIEP flap (mean flap weight, 613 ± 169 g). Mean age was 58 ± 11 years, mean follow-up time was 5 ± 1 years, and mean BMI was 24 ± 3 kg/m2 . DIEP flaps exhibited significantly weaker cutaneous vasodilation in response to local heating than contralateral breasts (median peak skin blood flow, 59 [25th-75th percentile, 36-71] a.u. for DIEP flaps versus 94 [74-141] a.u. for contralateral breasts; p < .001). The magnitude of the response was similar between reinnervated and noninnervated flaps (median peak skin blood flow, 55 [25th-75th percentile, 39-68] a.u. for reinnervated DIEP flaps versus 66 [36-77] a.u. for noninnervated DIEP flaps; p = .75). Of participants with reinnervated DIEP flaps, 90% perceived heat pain below the 50°C safety threshold, as compared to 36% of participants with noninnervated DIEP flaps (two-tailed p = .02). CONCLUSION: Our results suggest that free flap transfer causes longstanding impairment, yet not complete abolition, of both the sensory nerve-mediated and nitric oxide-dependent local heating-induced cutaneous vasodilatory systems. We found no statistical evidence that flap reinnervation improves the ability to raise skin blood flow in response to local heating.

Pressure Masks for Facial Scar Treatment after Oncological Reconstruction: Long-Term Patient Satisfaction and Quality of Life.

INTRODUCTION: With increasing incidence of facial skin cancer, more patients undergo facial reconstruction following Mohs micrographic surgery (MMS). Aesthetically unpleasing, thickened facial flaps, and disturbing scars can be treated with a pressure mask with inner silicone lining to help improve functional and aesthetic outcomes. However, data on long-term patient satisfaction and quality of life (QoL) following this treatment are lacking. METHODS: We aimed to assess long-term satisfaction and QoL of patients who underwent local flap reconstruction following MMS. Patients treated between January 2012 and October 2020 were invited to answer FACE-Q and SCAR-Q questionnaires. Demographic data, skin cancer type and location, type of reconstruction, postoperative complications, duration of pressure mask therapy, daily compliance, and additional scar treatment were collected to explore possible predictors. RESULTS: Of 92 eligible patients, 50 responded. Eighteen respondents were male (36%) and 32 were female (64%). Mean duration of pressure mask therapy was 10.20 ± 4.61 months. Patients were 61.14 ± 32.91 months after completion of pressure mask therapy upon participation. Patients whose reconstruction consisted of multiple flaps had significantly worse outcomes in social function (p = 0.012), scar appearance (p = 0.045), and scar symptoms (p = 0.008). A trend of increasing time since therapy completion predicting better outcomes was observed for all scales, and it was a significant predictor for better scar appearance (p = 0.001) and less scar symptoms (p = 0.001). CONCLUSION: Pressure mask treatment for facial flaps and scars following MMS results in good long-term patient satisfaction and QoL. Multiple local flaps, reflecting a larger skin defect postexcision, is a predictor for worse outcomes in social function, scar appearance, and symptoms. Increasing time is associated with increasing satisfaction, which reflects satisfactory and stable long-term effects of treatment, possibly combined with more acceptance of the result over time.

Medical Specialist Care Utilization Prior to the Explantation of Cosmetic Silicone Breast Implants: A Nationwide Retrospective Data Linkage Study.

BACKGROUND: Explantation is the proposed treatment for breast implant illness (BII). Little is known about which medical specialists are visited and what diagnoses are made before explantation is provided as the treatment. OBJECTIVES: This study investigated medical specialist care utilization in women with cosmetic breast implants who underwent explantation compared to women who chose breast implant replacement surgery and to women without breast implants. METHODS: Retrospective cohort study using data linkage with the Dutch Breast Implant Registry and the Dutch health insurance claims database. Visits to medical specialists were examined over the 3 years before explantation. A total of 832 explantation patients were matched and compared to 1463 breast implant replacement patients and 1664 women without breast implants. RESULTS: Explantation patients were more likely to have visited > 5 different medical specialties compared to both replacement patients (12.3% vs. 5.7%; p < 0.001) and women without breast implants (12.3% vs. 3.7%; p < 0.001). Among explantation patients, women who underwent explantation because of BII were more likely to have visited > 5 different medical specialties compared to women who underwent explantation because of other reasons (25.0% vs. 11.0%; p < 0.001). CONCLUSIONS: Women who underwent explantation of breast implants had higher utilization of medical specialist care in the years before explantation compared to women who underwent breast implant replacement surgery and women without breast implants. Medical specialist care use was especially high among women for whom BII was the registered reason for explantation. These findings suggest further research is needed into the link between BII and the use of medical specialist care. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Learning Sensory Nerve Coaptation in Free Flap Breast Reconstruction.

BACKGROUND: The aims of this study were to assess whether sensory nerve coaptation in free flap breast reconstruction is subject to learning, and to elucidate challenges of this technique. METHODS: In this single-center retrospective cohort study, we reviewed consecutive free flap breast reconstructions performed between March 2015 and August 2018. Data were extracted from medical records, and missing values were imputed. We assessed learning by exploring associations between case number and probability of successful nerve coaptation using a multivariable mixed-effects model. Sensitivity analysis was performed in a subgroup of cases with evidence of attempted coaptation. Recorded reasons for failed coaptation attempts were grouped into thematic categories. Multivariable mixed-effects models were used to examine associations between case number and postoperative mechanical detection threshold. RESULTS: Nerve coaptation was completed in 250 of 564 (44%) included breast reconstructions. Success rates varied considerably between surgeons (range 21-78%). In the total sample, the adjusted odds of successful nerve coaptation increased 1.03-fold for every unit increase in case number (95% confidence interval 1.01-1.05, p < 0.05), but sensitivity analysis refuted this apparent learning effect (adjusted odds ratio 1.00, 95% confidence interval 1.00-1.01, p = 0.34). The most frequently recorded reasons for failed nerve coaptation attempts were inability to locate a donor or recipient nerve. Postoperative mechanical detection thresholds showed a negligible, positive association with case number (estimate 0.00, 95% confidence interval 0.00-0.01, p < 0.05). CONCLUSION: This study does not provide evidence in support of a learning process for nerve coaptation in free flap breast reconstruction. Nevertheless, the identified technical challenges suggest that surgeons may benefit from training visual search skills, familiarizing with relevant anatomy, and practicing techniques for achieving tensionless coaptation. This study complements prior studies exploring therapeutic benefit of nerve coaptation by addressing technical feasibility.

Effect of Hearing Status on Concussion Knowledge and Attitudes of Collegiate Athletes.

CONTEXT: Collegiate athletes who are deaf or hard-of-hearing (D/HoH) are diagnosed with concussions at a similar rate as athletes who are hearing; however, little evidence exists on knowledge and attitudes of athletes who are D/HoH toward concussions. This study aimed to examine differences in knowledge of and attitudes toward concussions between athletes who are D/HoH and athletes who are hearing. DESIGN: Cross-sectional research design. METHODS: Of the 310 athletes who are D/HoH and 430 athletes who are hearing that were invited to participate, 90 athletes who are D/HoH, and 72 athletes who are hearing completed the survey. The Rosenbaum Concussion Knowledge and Attitudes Survey was used to quantify knowledge of and attitude toward concussions. The Rosenbaum Concussion Knowledge and Attitudes Survey consists of the concussion knowledge index (CKI) and the concussion attitudes index (CAI) subscales. Linear regressions were run to test the association of hearing status with CKI and CAI scores. Pearson correlations were performed to determine relationships between CKI and CAI for athletes who are D/HoH and athletes who are hearing. Alpha level was set a priori at P ≤ .05. RESULTS: Athletes who are hearing demonstrated a higher CKI component score (19.58 [2.19]) compared to athletes who are D/HoH (16.14 [3.31]; P < .001). There were no statistical differences in CAI between hearing groups (hearing: 57.18 [8.73], D/HoH: 55.97 [9.92]; P = .41). There was a moderate positive correlation between CKI and CAI (r = .58) for athletes who are D/HoH, while a weak positive correlation (r = .30) for athletes who are hearing was observed. CONCLUSIONS: Athletes who are D/HoH have poorer knowledge of concussions but similar attitudes toward concussion as that of athletes who are hearing. Current concussion educational interventions are in written or spoken form which may not be inclusive to athletes who are D/HoH. Health care professionals should consider an athlete's preferred communication mode to improve the efficiency and effectiveness of education.

What is the impact of miniscrew-assisted rapid palatal expansion on the midfacial soft tissues? A prospective three-dimensional stereophotogrammetry study.

OBJECTIVES: To evaluate the midfacial soft tissue changes of the face in patients treated with miniscrew-assisted rapid palatal expansion (MARPE). MATERIALS AND METHODS: 3D facial images and intra-oral scans (IOS) were obtained before expansion (T0), immediately after completion of expansion (T1), and 1 year after expansion (T2). The 3D images were superimposed and two 3D distance maps were generated to measure the midfacial soft tissue changes: immediate effects between timepoints T0 and T1 and overall effects between T0 and T2. Changes of the alar width were also measured and dental expansion was measured as the interpremolar width (IPW) on IOS. RESULTS: Twenty-nine patients (22 women, 7 men, mean age 25.9 years) were enrolled. The soft tissue in the regions of the nose, left of philtrum, right of philtrum, and upper lip tubercle demonstrated a statistically significant anterior movement of 0.30 mm, 0.93 mm, 0.74 mm, and 0.81 mm, respectively (p < 0.01) immediately after expansion (T0-T1). These changes persisted as an overall effect (T0-T2). The alar width initially increased by 1.59 mm, and then decreased by 0.08 mm after 1 year, but this effect was not significant. The IPW increased by 4.58 mm and remained stable 1 year later. There was no significant correlation between the increase in IPW and alar width (r = 0.35, p = 0.06). CONCLUSIONS: Our findings indicate that MARPE results in significant but small changes of the soft tissue in the peri-oral and nasal regions. However, the clinical importance of these findings is limited. CLINICAL RELEVANCE: MARPE is an effective treatment modality to expand the maxilla, incurring only minimal and clinically insignificant changes to the midfacial soft tissues.

Aesthetic Evaluation of Breast Reconstruction with Autologous Fat Transfer vs. Implants.

BACKGROUND: Autologous fat transfer (AFT) seems to be a new minimal invasive method for total breast reconstruction, yet how patients, surgeons, and laymen evaluate cosmesis is lacking. The aim of this study was to evaluate the aesthetic outcome of AFT (intervention group) for total breast reconstruction post-mastectomy, as compared to implant-based reconstruction (IBR) (control group). METHODS: A random and blinded 3D photographic aesthetic outcome study was performed on a selection of 50 patients, scored by three panels: plastic surgeons, breast cancer patients, and laymen. Secondary outcomes included agreement within groups and possible patient characteristics influencing scoring. RESULTS: Breast cancer patients and plastic surgeons did not differ in the aesthetic scores between the treatment groups. In contrast, the laymen group scored AFT patients lower than IBR patients (- 1.04, p < 0.001). Remarkably, mean given scores were low for all groups and overall agreement within groups was poor (ICC < 0.50). Higher scores were given when subjects underwent a bilateral reconstruction and if a mamilla was present. CONCLUSION: Evaluation of aesthetic outcomes varies greatly. Hence, aesthetic outcome remains a very personal measure and this emphasizes the importance of thorough patient counseling including information on achievable aesthetic results before starting a reconstructive procedure. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Influence of Personality on Health Complaints and Quality of Life in Women With Breast Implants.

BACKGROUND: A causal relation between systemic symptoms and breast implants has not been established. Psychological factors, such as personality and psychological distress, are strongly associated with the development of medically unexplained symptoms. It can be hypothesized that psychological factors may be related to the development of breast implant illness (BII). OBJECTIVES: This study was conducted to evaluate the correlation between self-reported health complaints, health- and breast-related quality of life (QoL), and personality, in women with cosmetic breast implants. METHODS: Women who attended the plastic surgery outpatient clinic of Maastricht University Medical Center between October 2020 and October 2021 for reasons related to their implants and women recruited for a BII study at the Center during this period were invited to participate in this study. Only women who underwent cosmetic breast augmentation were eligible. Participants completed a physical complaints score form and the BREAST-Q, SF-36, and EPQ-RSS questionnaires via an online survey. RESULTS: In total, 201 women completed the questionnaires. Extroversion and social desirability were predominant personality traits in women with breast implants, followed by neuroticism. Relatively high levels of neuroticism were found compared with normative data. Neuroticism correlated significantly with health status and breast-related QoL. Physical and mental health-related QoL had the strongest correlations with neuroticism (ß = -3.94, ß = -4.86, P < 0.001). CONCLUSIONS: Personality can play a role in the development of complaints. High levels of neuroticism are seen in cosmetic surgery patients and are negatively correlated with subjective health and patient-reported outcomes in women with breast implants. Therefore, neuroticism may be a factor in the development of BII.

Neuroimaging in Breast Implant Illness: An fMRI Pilot Study.

BACKGROUND: Some women with breast implants report systemic and cognitive symptoms known as breast implant illness (BII), which are very similar to those of fibromyalgia. Functional MRI (fMRI) has shown altered brain activity in fibromyalgia patients. OBJECTIVES: The aim of this pilot study was to investigate whether brain alterations could be observed in BII patients by fMRI. METHODS: Women aged 18 to 76 with silicone breast implants for cosmetic reasons were recruited through a Dutch online BII support organization (MKS) and through the Maastricht University Medical Center. Study participants comprised 12 women with BII and 12 women without symptoms. Participants completed questionnaires regarding demographic characteristics, medical history, psychosocial complaints (Four-Dimensional Symptom Questionnaire), cognitive failure (Mini-Mental State Examination), and pain intensity and pain-related disability (Chronic Pain Grade Scale). Subsequently, brain images of all participants were obtained by resting-state fMRI and diffusion tensor imaging in a 3-T MRI scanner (Siemens Medical System, Erlangen, Germany). RESULTS: Eleven BII patients and 12 healthy controls were included in the analysis. Baseline characteristics were similar in the 2 groups and the mean silicone exposure was 15 years. Patients scored significantly higher than controls on both pain intensity and disability. Patients scored worse on depression, somatization, distress, and anxiety compared with asymptomatic women. Mini-Mental State Examination scores were normal. However, the analyses of both functional connectivity and structural integrity showed no significant differences between the 2 groups. CONCLUSIONS: This pilot study showed no evidence of brain alterations in BII patients. However, patients scored significantly worse on psychosocial symptoms than controls. Psychological factors appear to play an important role in BII and should be further investigated.

Donor Site Satisfaction Following Autologous Fat Transfer for Total Breast Reconstruction.

BACKGROUND: With evolving breast cancer survival and patient preferences, it is essential that reconstructive surgeons worldwide continue searching for the best reconstruction technique for patients. Autologous fat transfer (AFT) is a relatively new technique for total breast reconstruction that has already proven to be effective and safe with all advantages of autologous tissue. However, little is known about the aesthetic results and satisfaction concerning donor sites. OBJECTIVES: The aim of this study was to measure donor site satisfaction following AFT for total breast reconstruction in breast cancer patients. METHODS: Between May and August of 2021, participants of the BREAST- trial who were at least 24 months after their final reconstruction surgery were invited to complete an additional survey concerning donor sites. The BODY-Q was utilized for data collection. Results of AFT patients were compared with a control group of implant-based reconstruction patients who did not have a donor site. RESULTS: A total of 51 patients (20 control, 31 intervention) completed the questionnaire. Satisfaction with body did not statistically differ between the groups. The most frequent complaint was contour irregularities (31 reports, 60.8%), with the least favorable donor site being thighs (23 reports, 53.5%) in the AFT group. CONCLUSIONS: Satisfaction with body did not differ between breast cancer patients receiving AFT or implant-based reconstruction, meaning that large-volume liposuction does not aesthetically affect the utilized donor sites. Nevertheless, reconstructive surgeons should be aware of possible donor site complications, especially contour irregularities at the thighs, and discuss this with their patients.

Chromosome 20 loss is characteristic of breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a very rare type of T-cell lymphoma that is uniquely caused by a single environmental stimulus. Here, we present a comprehensive genetic analysis of a relatively large series of BIA-ALCL (n = 29), for which genome-wide chromosomal copy number aberrations (CNAs) and mutational profiles for a subset (n = 7) were determined. For comparison, CNAs for anaplastic lymphoma kinase (ALK)- nodal anaplastic large cell lymphomas (ALCLs; n = 24) were obtained. CNAs were detected in 94% of BIA-ALCLs, with losses at chromosome 20q13.13 in 66% of the samples. Loss of 20q13.13 is characteristic of BIA-ALCL compared with other classes of ALCL, such as primary cutaneous ALCL and systemic type ALK+ and ALK- ALCL. Mutational patterns confirm that the interleukin-6-JAK1-STAT3 pathway is deregulated. Although this is commonly observed across various types of T-cell lymphomas, the extent of deregulation is significantly higher in BIA-ALCL, as indicated by phosphorylated STAT3 immunohistochemistry. The characteristic loss of chromosome 20 in BIA-ALCL provides further justification to recognize BIA-ALCL as a separate disease entity. Moreover, CNA analysis may serve as a parameter for future diagnostic assays for women with breast implants to distinguish seroma caused by BIA-ALCL from other causes of seroma accumulation, such as infection or trauma.

The unexpected dominance of secondary over primary nucleation.

It is still a challenge to control the formation of particles in industrial crystallization processes. In such processes, new crystals can be generated either by primary or secondary nucleation. While in continuous stirred tank crystallization processes, secondary nucleation is thought to occur due to the shear or attrition of already present larger crystals; in antisolvent crystallization processes, where mixing at the inlets locally causes high supersaturations, primary nucleation is understood to be the main mechanism. We aim to show here that secondary nucleation is the dominant nucleation mechanism, even under conditions that are generally considered to be dominated by primary nucleation mechanisms. Measurements of primary and secondary nucleation rates under similar industrial crystallization conditions of sodium bromate in water, sodium chloride in water, glycine in water and isonicotinamide in ethanol show that the secondary nucleation rate is at least 6 orders of magnitude larger in all these systems. Furthermore, seeded fed-batch and continuous antisolvent crystallizations of sodium bromate under high local supersaturation, seeded with crystals of a specific handedness, result in a close to chirally pure crystalline product with the same handedness. This shows that indeed, enantioselective secondary nucleation is the dominant mechanism in these antisolvent crystallizations. It is even possible to use the enantioselective secondary nucleation mechanism to control the product chirality in such a process, making antisolvent crystallization a viable crystallization-enhanced deracemization technique, having a superior productivity compared to other crystallization-enhanced deracemization methods. Our finding of a dominant secondary nucleation mechanism, rather than primary nucleation, will have a strong impact on nucleation control strategies in industrial crystallization processes.

Cancer worry after facial nonmelanoma skin cancer resection and reconstruction: A 1-year prospective study.

OBJECTIVE: Nonmelanoma skin cancer (NMSC) is one of the most diagnosed cancers in the world, with the number of new occurrences rising every year. Most patients with facial skin cancer experience cancer-related worry. Yet, little is known about their worry during the period after cancer treatment. This study aimed to assess the long-term change of cancer worry after surgical treatment in patients with NMSC. METHODS: Patients undergoing surgery for facial NMSC between December 2017 and March 2020 were asked to complete the FACE-Q Skin Cancer-Cancer Worry scale before (baseline), 3-month, and 1-year post-surgery. RESULTS: A total of 151 patients completed the baseline and 3-month, and 99 (65.6%) the 1-year post-operative survey. A significant decrease in cancer worry score was seen between baseline and 3-month post-surgery (p < 0.001). No difference was found between the 3-month and 1-year post-surgery scores (p = 0.78). Less improvement in cancer worry was seen for patients who had one facial skin cancer in their medical history (p = 0.001) and patients who had a history of facial surgery (p < 0.001). CONCLUSION: Post-surgery patients still experience cancer worry. Therefore, targeted counseling might be of value when coping with cancer-related concerns. Patients with a history of facial NMSC and patients with a history of facial surgery might benefit from additional counseling.

Development, diagnostic performance, and interobserver agreement of a 18F-flurpiridaz PET automated perfusion quantitation system.

BACKGROUND: Computerized methodologies standardize the myocardial perfusion imaging (MPI) interpretation process. METHODS: To develop an automated relative perfusion quantitation approach for 18F-flurpiridaz, PET MPI studies from all phase III trial participants of 18F-flurpiridaz were divided into 3 groups. Count distributions were obtained in N = 40 normal patients undergoing pharmacological or exercise stress. Then, N = 90 additional studies were selected in a derivation group. Following receiver operating characteristic curve analysis, various standard deviations below the mean normal were used as cutoffs for significant CAD, and interobserver variability determined. Finally, diagnostic performance was compared between blinded visual readers and blinded derivations of automated relative quantitation in the remaining N = 548 validation patients. RESULTS: Both approaches yielded comparable accuracies for the detection of global CAD, reaching 71% and 72% by visual reads, and 72% and 68% by automated relative quantitation, when using CAD ≥ 70% or ≥ 50% stenosis for significance, respectively. Similar results were observed when analyzing individual coronary territories. In both pharmacological and exercise stress, automated relative quantitation demonstrated significantly more interobserver agreement than visual reads. CONCLUSIONS: Our automated method of 18F-flurpiridaz relative perfusion analysis provides a quantitative, objective, and highly reproducible assessment of PET MPI in normal and CAD subjects undergoing either pharmacological or exercise stress.

Efficacy of Miniscrew-Assisted Rapid Palatal Expansion (MARPE) in late adolescents and adults with the Dutch Maxillary Expansion Device: a prospective clinical cohort study.

OBJECTIVES: To provide a higher degree of evidence on the efficacy of Miniscrew-Assisted Rapid Palatal Expansion (MARPE) in late adolescents and adults, thereby applying the Dutch Maxillary Expansion Device (D-MED). MATERIALS AND METHODS: D-MED was developed as an individualized, 3D-designed, and fabricated MARPE appliance supported by 4 palatal miniscrews. Patients from the age of 16 onwards with transverse maxillary deficiency were enrolled consecutively. Pre-expansion and immediate post-expansion CBCTs and intra-oral scans were acquired and measurements of skeletal, alveolar, and dental expansion as well as dental and periodontal side-effects were performed. RESULTS: Thirty-four patients were enrolled (8 men, 26 women) with mean age 27.0 ± 9.4 years. A success rate of 94.1% was achieved (32/34 patients). The mean expansion duration, or mean observation time, was 31.7 ± 8.0 days. The mean expansion at the maxillary first molars (M1) and first premolars (P1) was 6.56 ± 1.70 mm and 4.19 ± 1.29 mm, respectively. The expansion was 60.4 ± 20.1% skeletal, 8.1 ± 27.6% alveolar, and 31.6 ± 20.1% dental at M1 and 92.2 ± 14.5% skeletal, 0.0 ± 18.6% alveolar, and 7.8 ± 17.7% dental at P1, which was both statistically (p < 0.001) and clinically significant. Buccal dental tipping (3.88 ± 3.92° M1; 2.29 ± 3.89° P1), clinical crown height increase (0.12 ± 0.31 mm M1; 0.04 ± 0.22 mm P1), and buccal bone thinning (- 0.31 ± 0.49 mm M1; - 0.01 ± 0.45 mm P1) were observed, while root resorption could not be evaluated. CONCLUSIONS: MARPE by application of D-MED manifested its efficacy in a prospective clinical setting, delivering a high amount of skeletal expansion with limited side-effects in late adolescents and adults. CLINICAL RELEVANCE: Higher quality evidence is supportive of MARPE as a safe and successful non-surgical treatment option for transverse maxillary deficiency.

The Use of the FACE-Q Aesthetic: A Narrative Review.

INTRODUCTION: In the past decade there has been an increasing interest in the field of patient-reported outcome measures (PROMs) which are now commonly used alongside traditional outcome measures, such as morbidity and mortality. Since the FACE-Q Aesthetic development in 2010, it has been widely used in clinical practice and research, measuring the quality of life and patient satisfaction. It quantifies the impact and change across different aspects of cosmetic facial surgery and minimally invasive treatments. We review how researchers have utilized the FACE-Q Aesthetic module to date, and aim to understand better whether and how it has enhanced our understanding and practice of aesthetic facial procedures. METHODS: We performed a systematic search of the literature. Publications that used the FACE-Q Aesthetic module to evaluate patient outcomes were included. Publications about the development of PROMs or modifications of the FACE-Q Aesthetic, translation or validation studies of the FACE-Q Aesthetic scales, papers not published in English, reviews, comments/discussions, or letters to the editor were excluded. RESULTS: Our search produced 1189 different articles; 70 remained after applying in- and exclusion criteria. Significant findings and associations were further explored. The need for evidence-based patient-reported outcome caused a growing uptake of the FACE-Q Aesthetic in cosmetic surgery and dermatology an increasing amount of evidence concerning facelift surgery, botulinum toxin, rhinoplasty, soft tissue fillers, scar treatments, and experimental areas. DISCUSSION: The FACE-Q Aesthetic has been used to contribute substantial evidence about the outcome from the patient perspective in cosmetic facial surgery and minimally invasive treatments. The FACE-Q Aesthetic holds great potential to improve quality of care and may fundamentally change the way we measure success in plastic surgery and dermatology. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .