Facial Transplantation: Nonimmune-Related Hyperacute Graft Failure-The Role of Perfusion Injury: A Case Report.

BACKGROUND: The aim of this study was to report the first case of acute facial allograft transplantation (facial allograft transplantation) failure with allograft removal and autologous free-flap reconstruction. METHODS: A 49-year-old female patient affected by neurofibromatosis type 1 with a massive neurofibroma infiltrating the whole left hemiface was planned for FAT for the left hemiface including the auricle, all skin and soft tissues from the temporal region, periorbital and nasal region, and up to the perioral area. The maxillary process of the zygomatic bone, left hemimaxilla, and hemimandible from contralateral parasyphysis to the incisura mandibulae were also included. RESULTS: Total surgical time was 26 hours. There were 2 intraoperative arterial thromboses that were solved with new anastomoses and sufficient flap perfusion. On postoperative day 2, the allograft became pale with suspected arterial occlusion and the patient returned to the operative room for exploration no flow into the FAT was found. The allograft was removed and the recipient site reconstructed with a skin-grafted composite left latissimus dorsi-serratus anterior flap. CONCLUSIONS: Hyperacute loss of FAT is a very dramatic event, and the activation of a backup surgical plan is crucial to save patient's life, give a reasonable temporary reconstruction, and return on the waiting-list for a second face transplantation.

Skin grafted latissimus dorsi flap for reconstruction of lateral aesthetic units of the face.

Reconstruction of large defects of the lateral region of the face is rather challenging due to the unique color, texture, and thickness of soft tissues in this area. Microsurgical free flaps represent the gold standard, providing superior functional and aesthetic restoration. Purpose of this study was to assess reliability of skin-grafted latissimus dorsi (LD) flap, for a pleasant and symmetric reconstruction of the lateral aesthetic units of the face compared to a control group of patients addressed to perforator flaps. From November 2008 to June 2012, 5 patients underwent skin-grafted LD flap reconstruction of defects involving the lateral aesthetic units of the face, with 8.1 ± 0.5 × 9.7 ± 1.3 cm mean size. A 1-to-4 Likert scale was used to assess skin color, texture, shape, and bulkiness. Using the Pressure-Specified Sensory Device epicritic, proprioceptive, and protopathic sensitivities were tested. Outcomes were compared with those of a control group of 5 patients addressed to reconstruction with perforator flaps (3 anterolateral thigh flap, 2 vertical deep inferior perforator flap). At mean 21-month follow-up all flaps healed uneventfully without need for revisions, all developing more satisfactory results in terms of skin color (P = 0.028) and texture (P = 0.021) match, shape (P = 0.047) and bulkiness (P = 0.012) compared with perforator flaps. No differences in epicritic, proprioceptive, and protopathic sensitivities were observed (P > 0.05) between the two groups. Skin-grafted LD flap may be a suitable option for reconstruction of wide defects of the lateral aesthetic units of the face.

Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics.

Mounting evidence points towards a crucial role of the kynurenine pathway (KP) in the altered gut-brain axis (GBA) balance in severe mental illness (SMI, namely depression, bipolar disorder, and schizophrenia) and cardiometabolic comorbidities. Preliminary evidence shows that serotonergic psychedelics and their analogues may hold therapeutic potential in addressing the altered KP in the dysregulated GBA in SMI and comorbidities. In fact, aside from their effects on mood, psychedelics elicit therapeutic improvement in preclinical models of obesity, metabolic syndrome, and vascular inflammation, which are highly comorbid with SMI. Here, we review the literature on the therapeutic modulation of the KP in the dysregulated GBA in SMI and comorbidities, and the potential application of psychedelics to address the altered KP in the brain and systemic dysfunction underlying SMI and comorbidities. Psychedelics might therapeutically modulate the KP in the altered GBA in SMI and comorbidities either directly, via altering the metabolic pathway by influencing the rate-limiting enzymes of the KP and affecting the levels of available tryptophan, or indirectly, by affecting the gut microbiome, gut metabolome, metabolism, and the immune system. Despite promising preliminary evidence, the mechanisms and outcomes of the KP modulation with psychedelics in SMI and systemic comorbidities remain largely unknown and require further investigation. Several concerns are discussed surrounding the potential side effects of this approach in specific cohorts of individuals with SMI and systemic comorbidities.

Epidemiological and Molecular Investigation of the Heater-Cooler Unit (HCU)-Related Outbreak of Invasive Mycobacterium chimaera Infection Occurred in Italy.

BACKGROUND: From 2013 onwards, a large outbreak of Mycobacterium chimaera (MC) invasive infection, which was correlated with the use of contaminated heater-cooler units (HCUs) during open chest surgery, was reported from all over the world. Here, we report the results of the epidemiological and molecular investigations conducted in Italy after the alarm raised about this epidemic event. METHODS: MC strains isolated from patients or from HCU devices were characterized by genomic sequencing and molecular epidemiological analysis. RESULTS: Through retrospective epidemiological analysis conducted between January 2010 and December 2022, 40 possible cases of patients infected with MC were identified. Thirty-six strains isolated from these patients were analysed by whole genome sequencing (WGS) and were found to belong to the genotypes 1.1 or 1.8, which are the genotypes correlated with the outbreak. Most of the cases presented with prosthetic valve endocarditis, vascular graft infection or disseminated infection. Among the cases found, there were 21 deaths. The same analysis was carried out on HCU devices. A total of 251 HCUs were found to be contaminated by MC; genotypes 1.1 or 1.8 were identified in 28 of those HCUs. CONCLUSIONS: To ensure patients' safety and adequate follow-up, clinicians and general practitioners were made aware of the results and public health measures, and recommendations were issued to prevent further cases in the healthcare settings. The Italian Society of Cardiac Surgery performed a national survey to assess the incidence of HCU-related MC prosthetic infections in cardiac surgery. No cases were reported after HCU replacement or structural modification and disinfection and possibly safe allocation outside surgical rooms.

Modulation of DNA methylation and protein expression in the prefrontal cortex by repeated administration of D-lysergic acid diethylamide (LSD): Impact on neurotropic, neurotrophic, and neuroplasticity signaling.

AIM: Psychedelic compounds elicit relief from mental disorders. However, the underpinnings of therapeutic improvement remain poorly understood. Here, we investigated the effects of repeated lysergic acid diethylamide (LSD) on whole-genome DNA methylation and protein expression in the mouse prefrontal cortex (PFC). METHODS: Whole genome bisulphite sequencing (WGBS) and proteomics profiling of the mouse prefrontal cortex (PFC) were performed to assess DNA methylation and protein expression changes following 7 days of repeated LSD administration (30 µg/kg/day); a treatment we previously found to potentiate excitatory neurotransmission and to increase dendritic spine density in the PFC in mice. qRT-PCR was employed to validate candidate genes detected in both analyses. RESULTS: LSD significantly modulated DNA methylation in 635 CpG sites of the mouse PFC, and in an independent cohort the expression level of 178 proteins. Gene signaling pathways affected are involved in nervous system development, axon guidance, synaptic plasticity, quantity and cell viability of neurons and protein translation. Four genes and their protein product were detected as differentially methylated and expressed, and their transcription was increased. Specifically, Coronin 7 (Coro7), an axon guidance cue; Penta-EF-Hand Domain Containing 1 (Pef1), an mTORC1 and cell cycle modulator; Ribosomal Protein S24 (Rps24), required for pre-rRNA maturation and biogenesis of proteins involved with cell proliferation and migration, and Abhydrolase Domain Containing 6, Acylglycerol Lipase (Abhd6), a post-synaptic lipase. CONCLUSIONS: LSD affects DNA methylation, altering gene expression and protein expression related to neurotropic-, neurotrophic- and neuroplasticity signaling. This could represent a core mechanism mediating the effects of psychedelics.

Chest wall infiltration is a critical prognostic factor in breast implant-associated anaplastic large-cell lymphoma affected patients.

BACKGROUND: Breast implant-associated anaplastic large-cell lymphoma is a rare disease with a favourable prognosis if adequately treated. Same staged patients have usually a similar prognosis and outcomes, but in our experience, IIA-staged patients have a wider prognosis with outcomes that vary from complete disease response to death. This study aimed to understand and identify all the factors that could influence the prognosis of this group of patients and verify if their prognosis matches the stage they belong to. MATERIAL AND METHODS: Patients in stage IIA have been divided into two subgroups: IIAb with lymphoma extension towards the glandular tissue and IIAcw with tumour extension towards the chest-wall. The overall survival (OS) and event-free survival (EFS) of 64 BIA-ALCL cases were evaluated for each staged group. RESULTS: Significant differences of OS and EFS between IIAb and IIAcw patients (log-rank p = 0.046 and log-rank p = 0.018, respectively) were observed and poor prognosis joined IIAcw- and IV-staged patients. CONCLUSION: Chest-wall infiltration is a critical prognostic factor in BIA-ALCL patients as it influences the possibility of performing a surgical radical tumour extirpation. Our results could represent valid assistance for the physicians in choosing the most appropriate BIA-ALCL prognostic category and treatment and could promote further wider studies to provide stronger evidence on a possible revision of the MDA TNM classification.

The "Type V" skin-sparing mastectomy for upper quadrant skin resections.

Skin-sparing mastectomies (SSMs) are classified according to the type of incision and breast size. In large breasts, if cancer is superficially located in the upper quadrants, SSM type IV is not indicated, because tumor resection interferes with skin flap pattern. For these patients, a modified Wise-pattern SSM has been developed to achieve immediate breast reconstruction. Twenty-four patients, 14 with tumor in the superior-lateral, 7 in the superior-medial, and 3 in the inferior-lateral quadrant, were operated on with modified SSM incisions. To replace the skin area removed with mastectomy from the upper quadrants, a similar size area from the lower pole was used. No local or distant recurrences occurred, with a mean follow-up of 27 months. Natural breast shape was achieved in all cases. Our procedure allows for a skin-sparing mastectomy (SSM type V) with immediate reconstruction, achieving a natural breast shape also in this group of patients previously excluded.

The Crucial Role of Surgical Treatment in BIA-ALCL Prognosis in Early- and Advanced-Stage Patients.

BACKGROUND: Studies on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) are trying to optimize medical and surgical treatments for early and advanced stages of this disease. The aim of this article is to share the experience gathered on the authors' prospectively collected 46 well-documented cases. METHODS: Italian physicians are obliged to report BIA-ALCL cases to the Italian Ministry of Health. Because of this cooperation with health care professionals, the competent authority has coordinated and centralized the collection of information for each patient in 46 cases of BIA-ALCL. Statistical analyses with cumulative incidence and corresponding 95 percent confidence interval are provided for each year, dividing the number of new cases that occurred in a defined year and the population at risk of experiencing BIA-ALCL during the same year. RESULTS: The mean time to the onset of symptoms is reduced to 6.4 ± 3.77 years (range, 1 to 22 years). Increased knowledge has also shortened the average time to diagnosis, at 7.2 ± 3.71 years (range, 2 to 22 years). A late seroma appears in 91 percent of cases. The patient who died underwent limited surgery. The Italian incidence has been estimated as 2.8 per 100,000 patients receiving implants (95 percent CI, 0.88 to 4.84) in 2015; 2.1 (95 percent CI, 0.43 to 3.86) in 2016; 3.2 (95 percent CI, 1.11 to 5.31) in 2017; and 3.5 (95 percent CI, 1.36 to 5.78) in 2018. CONCLUSION: Although the number of cases has risen slightly, BIA-ALCL is still a rare disease with a stable incidence, easily recognized and with a favorable prognosis also in advanced stages if complete surgical excision is performed.

22 Cases of Breast Implant-Associated ALCL: Awareness and Outcome Tracking from the Italian Ministry of Health.

BACKGROUND: To date, 359 cases of anaplastic large cell lymphoma (ALCL) in women with breast implants (breast implant-associated ALCL [BIA-ALCL]) worldwide have been reported among more than 10 million patients who have received implants, but health care authorities suspect this is a possible underestimation, and the limited number of cases makes it difficult to clarify its cause. The General Directorate of Medical Devices and Pharmaceutical Services of the Italian Ministry of Health has examined and studied the Italian BIA-ALCL cases. METHODS: An official document has been diffused to all medical associations, aiming at encouraging all physicians to notify each BIA-ALCL case. A retrospective study has been performed on the notified BIA-ALCL cases collected in the database named Dispovigilance. RESULTS: Research on Dispovigilance returns a list of 22 BIA-ALCL cases. The mean patient age was 49.6 years (range, 30 to 71 years). The average time to the onset of the symptoms was 6.8 years (range, 1 to 22 years). The average time to diagnosis was 7.8 years (range, 4 to 22 years). The estimated incidence of the Italian BIA-ALCL cases related to 2015 is 2.8 per 100,000 patients. CONCLUSIONS: The pathogenesis of BIA-ALCL remains unknown. The establishment of a national breast implant registry is needed to better understand some aspects of this disease. Future genetic studies on the population affected could clarify why only some patients with implants develop this disease.

MBN 2016 Aesthetic Breast Meeting BIA-ALCL Consensus Conference Report.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon neoplasia occurring in women with either cosmetic or reconstructive breast implants. The actual knowledge about BIA-ALCL deriving from the literature presents several limits, and it remains difficult to make inferences about BIA-ALCL epidemiology, cause, and pathogenesis. This is the reason why the authors decided to organize an evidence-based consensus conference during the Maurizio Bruno Nava (MBN 2016) Aesthetic Breast Meeting held in Milan in December of 2016. Twenty key opinion leaders in the field of plastic surgery from all over the world have been invited to express and discuss their opinion about some key questions on BIA-ALCL, trying to reach a consensus about BIA-ALCL cause, pathogenesis, diagnosis, and treatment in light of the actual best evidence.

Global Adverse Event Reports of Breast Implant-Associated ALCL: An International Review of 40 Government Authority Databases.

BACKGROUND: Tracking world cases of breast implant-associated anaplastic large cell lymphoma (ALCL) is currently limited to patient registries at a few academic centers, dependent upon patient referral and case reports in the literature. The purpose of this study was to review and compare federal database adverse event reports of breast implant-associated ALCL encompassing the major breast implant markets worldwide. METHODS: Federal implantable device regulatory bodies were contacted and database queries were performed for 40 countries. Demographics, device characteristics, pathology, treatment modalities, and outcomes were assessed when available. RESULTS: For the countries queried, 363 unique cases were reported for breast implant-associated ALCL. Search terms "anaplastic" and "ALCL" were queried of the U.S. Manufacturer and User Facility Device Experience (MAUDE) database and yielded 258 unique cases as of September 2015, of which only 130 had pathologic markers performed. Implant surface was textured significantly more than smooth (50 percent versus 4.2 percent; p = 0.0001). Treatment, when reported (n = 136), included explantation [n = 125 (91.9 percent)], chemotherapy [n = 42 (30.8 percent)], radiation therapy [n = 25 (18.4 percent)], and/or stem cell transplant [n = 9 (6.6 percent)], and five deaths were reported. CONCLUSIONS: Federal reporting of breast implant-associated ALCL has limitations in providing clinical history, treatment, and oncologic follow-up. Worldwide and country-specific total and textured implant sales data are needed to determine critical incidence and prevalence analysis. International multi-institutional collaborations and centralized tissue consortiums working in concert with federal authorities are necessary to acquire accurate complete data on breast implant-associated ALCL.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Proposal for a Monitoring Protocol.

BACKGROUND: The authors report four cases of breast implant-associated anaplastic large cell lymphoma (ALCL) from a single institution and propose a multidisciplinary protocol. METHODS: From 2012 to 2014, four breast implant-associated ALCL cases were diagnosed. The authors performed the original operation, and no patients were referred to their practice. Cases 1, 2, and 4 were CD4/CD30/ALK ALCL with previous textured-implant reconstruction, whereas case 3 was CD8/CD30/ALK ALCL with previous polyurethane-implant augmentation. A retrospective study of all patients who underwent breast implant positioning was performed to identify any misdiagnosed cases. RESULTS: Of 483 patients, 226 underwent reconstruction with latissimus dorsi flap and prosthesis, 115 had skin-sparing/nipple-sparing mastectomy and prosthesis, 117 underwent an expander/implant procedure, and 25 underwent breast augmentation. Fifty-eight cases (12 percent) underwent implant replacement for capsular contracture, 15 (3.1 percent) experienced late-onset seroma, and four (0.83 percent) had both capsular contracture and seroma. Seventy-seven symptomatic patients (16 percent) underwent surgical revision (capsulectomy/capsulotomy) and/or seroma evacuation. The second look on histologic specimens did not identify misdiagnosed cases. A multidisciplinary protocol for suspected implant-associated ALCL was established. Ultrasound and cytologic examinations are performed in case of periprosthetic effusion. If implant-associated ALCL is diagnosed, implant removal with capsulectomy is performed. If disseminated disease is detected through positron emission tomography/computed tomography of the total body, the patient is referred to the oncology department. CONCLUSIONS: A multidisciplinary protocol is mandatory for both early diagnosis and patient management. Until definitive data emerge regarding the exact etiopathogenesis of breast implant-associated ALCL, the authors suggest offering only autologous reconstruction if patients desire it. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Nipple-areola complex cutaneous sensitivity: a systematic approach to classification and breast volume.

INTRODUCTION: The aim of our study was to develop a systematic approach to provide a data bank on normative cutaneous pressure thresholds of the nipple-areola complex (NAC) in different breast volumes and a classification of the NAC sensitivity function. PATIENTS AND METHODS: A population of 150 Caucasian women stratified in five groups of 30 subjects according to the Lalardie-Jouglard classification of breast volume was enrolled in our study. A single evaluator (B.L.) performed breast volume assessments using the BREAST-V and sensory testing on NACs with Pressure-Specified Sensory Device; static and moving one- and two-point discriminations of nipple and areola were collected from each group. Statistical analysis using mixed effects model was performed with significant p-values <0.05. RESULTS: Nipple was found to be more sensitive than areola for both static and moving one-point tests. From our analyses emerged an inverse relationship between skin pressure thresholds and breast volume, with NACs from small breasts (group A) statistically more sensitive than NACs from macromastia women (group E). Properly, the group A women were found to be 0.42, 1.89, 4.98, and 9.55 times progressively more sensitive (p < 0.001) than groups B, C, D, and E, respectively, for quickly adapting fibers of nipple, and 0.58, 1.97, 4.97, and 8.67 times more sensitive (p < 0.001) than groups B, C, D, and E, respectively, for quickly adapting fibers of areola. The sensitivity function of the nipple and areola was classified as high (first degree), medium (second degree), and low (third degree) according to mean ± standard deviation of the overall values. CONCLUSION: Our study first provides a complete data bank of normative NAC sensitivity in a wide range of breast volumes, and gives three degrees of classification of NAC sensitivity function.

Long-term sensory recovery of nipple-areola complex following superolateral pedicled reduction mammaplasty.

BACKGROUND: The aim of this study was to investigate nipple-areola complex sensation at 48-month follow-up following superolateral pedicled reduction mammaplasty using the pressure-specified sensory device. METHODS: Data regarding nipple-areola complex sensation for static and moving one- and two-point discrimination were collected from 30 active group hypertrophic-breasted patients undergoing superolateral pedicled reduction mammaplasty preoperatively, at 6 months, and at 48 months, and from a control group of 30 unoperated women with normal-sized breasts. Breast volume was assessed using the BREAST-V instrument. RESULTS: For the nipple, static one-point discrimination showed that mean pressure thresholds for the active group at 48 months were 4.10 and 4.19 times higher than preoperatively and in the control group (p<0.001), respectively; moving one-point discrimination showed that mean pressure thresholds for the active group at 48 months were 4.08 and 3.23 times higher than preoperatively and in the control group (p<0.001), respectively. For the areola, static one-point discrimination showed that mean pressure thresholds in the active group at 48 months were 4.12 and 4.83 times higher than preoperatively and in the control group (p<0.001), respectively; moving one-point discrimination showed that mean pressure thresholds from the active group at 48 months were 4.56 and 4.46 times higher than preoperatively and in the control group (p<0.001), respectively. CONCLUSIONS: Despite a slight worsening at 6 months after surgery, patients who had undergone superolateral pedicled reduction mammaplasty showed significant nipple-areola complex sensibility reduction at 48-month follow-up. Although the nipple-areola complex of hypertrophic-breasted patients was seen to be nonsignificantly less sensitive than normal-sized breasts, a significant decrease of sensation was observed following reduction mammaplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The BREAST-V: a unifying predictive formula for volume assessment in small, medium, and large breasts.

BACKGROUND: Breast volume assessment enhances preoperative planning of both aesthetic and reconstructive procedures, helping the surgeon in the decision-making process of shaping the breast. Numerous methods of breast size determination are currently reported but are limited by methodologic flaws and variable estimations. The authors aimed to develop a unifying predictive formula for volume assessment in small to large breasts based on anthropomorphic values. METHODS: Ten anthropomorphic breast measurements and direct volumes of 108 mastectomy specimens from 88 women were collected prospectively. The authors performed a multivariate regression to build the optimal model for development of the predictive formula. The final model was then internally validated. A previously published formula was used as a reference. RESULTS: Mean (±SD) breast weight was 527.9 ± 227.6 g (range, 150 to 1250 g). After model selection, sternal notch-to-nipple, inframammary fold-to-nipple, and inframammary fold-to-fold projection distances emerged as the most important predictors. The resulting formula (the BREAST-V) showed an adjusted R of 0.73. The estimated expected absolute error on new breasts is 89.7 g (95 percent CI, 62.4 to 119.1 g) and the expected relative error is 18.4 percent (95 percent CI, 12.9 to 24.3 percent). Application of reference formula on the sample yielded worse predictions than those derived by the formula, showing an R of 0.55. CONCLUSIONS: The BREAST-V is a reliable tool for predicting small to large breast volumes accurately for use as a complementary device in surgeon evaluation. An app entitled BREAST-V for both iOS and Android devices is currently available for free download in the Apple App Store and Google Play Store. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.