Emerging roles of SARS-CoV-2 Spike-ACE2 in immune evasion and pathogenesis.

The COVID-19 pandemic, caused by SARS-CoV-2, has caused an estimated 5 billion infections and 20 million deaths by respiratory failure. In addition to the respiratory disease, SARS-CoV-2 infection has been associated with many extrapulmonary complications not easily explainable by the respiratory infection. A recent study showed that the SARS-CoV-2 spike protein, which mediates cell entry by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, signals through ACE2 to change host cell behavior. In CD8+ T cells, spike-dependent ACE2-mediated signaling suppresses immunological synapse (IS) formation and impairs their killing ability, leading to immune escape of virus-infected cells. In this opinion article, we discuss the consequences of ACE2 signaling on the immune response and propose that it contributes to the extrapulmonary manifestations of COVID-19.

Impact of Smoking on Salivary Lipid Profile and Oxidative Stress in Young Adults: A Comparative Analysis between Traditional Cigarettes, E-Cigarettes, and Heat-Not-Burn Products.

BACKGROUND Smoking nicotine is considered to be one of the most harmful addictions, leading to the development of a number of health complications, including many pathologies in the oral cavity. The aim of this study was to examine the effect of smoking traditional cigarettes, e-cigarettes, and heat-not-burn products on profiles of salivary lipids and lipid peroxidation products in the unstimulated and stimulated saliva of healthy young adults with a smoking habit of up to 3 years. MATERIAL AND METHODS We enrolled 3 groups of 25 smoking patients each and a control group matched for age, gender, and oral status. In saliva collected from patients from the study groups and participants from the control group, the concentrations of sphingolipids: sphingosine, sphinganine, sphingosine-1-phosphate, ceramides, and salivary lipid peroxidation products - malondialdehyde (MDA) and 4-hydroxynonenal (HNE) - were measured. The normality of distribution was assessed using the Shapiro-Wilk test. For comparison of the results, one-way analysis of variance (ANOVA) followed by post hoc Tukey test was used. RESULTS We demonstrated that each type of smoking causes a decrease in the concentration of salivary lipids, and there was an increased concentration of salivary MDA and 4-HNE. CONCLUSIONS Smoking in the initial period of addiction leads to an increase in the concentration of lipid peroxidation products through increased oxidative stress, leading to disturbance of the lipid balance of the oral cavity (eg, due to damage to cell membranes).

Vaccinology in the post-COVID-19 era.

The COVID-19 pandemic is a shocking reminder of how our world would look in the absence of vaccination. Fortunately, new technologies, the pace of understanding new and existing pathogens, and the increased knowledge of the immune system allow us today to develop vaccines at an unprecedented speed. Some of the vaccine technologies that are fast-tracked by the urgency of COVID-19 may also be the answer for other health priorities, such as antimicrobial resistance, chronic infections, and cancer, that the post-COVID-19 world will urgently need to face. This perspective analyzes the way COVID-19 is transforming vaccinology and the opportunities for vaccines to have an increasingly important role in health and well-being.

Evaluation of modulation of immunity by lymph node transfer: A preliminary histological evidence in lymphedema patients.

BACKGROUND: The exact knowledge of the local biological and immunological effects of vascularized lymph node transfer (VLNT) continues to be an emerging science but a positive control positive control over infectious and immune-mediated processes is often advocated. Knowing the characterization of the inflammatory infiltrate associated with lymphedema, the aim of this paper is to verify the hypothesis that VLNT is able to modulate the inflammatory and immune microenvironment of lymphedematous tissue by evaluating any modification of the local inflammatory cell infiltrate. PATIENTS AND METHODS: A prospectively database of patients who received VLN transfer for lower extremity lymphedema between January 2018 and December 2020 was reviewed. Nine patients diagnosed with extremities' stage II secondary lymphedema were included, with a mean age of 55.3 (range 39-66 years) years. Gastroepiploic lymph node transfer was performed in all patients and transferred heterotopically. Full thickness 6-mm skin punch biopsies were obtained from all voluntary lymph node transfer patients at identical sites of the lymphedematous limb during the surgical procedure of VLNT (T0) and 1 year later (T1). Immunohistochemistry was performed using antibodies against the following markers: anti-CD3; anti-CD4; anti-CD8; anti-CD68. Data at T0 were compared to those at T1. RESULTS: Post-operative course was uneventful in all cases experiencing a significant reduction (almost a third) in terms of cellulitis episodes: The median duration of follow-up for patients was 28.3 months (range 12-40). The analysis of the density of the inflammatory cells as a whole revealed a significant reduction at T1 compared to T0. Specifically, CD3 expression levels turned from 16.36 ± 3.421 (cells/mm2 ) pre-operatively to 7.6 ± 1.511 (cells/mm2 ) post-operatively (p < .0001). CD4+ cells turned from 7.270 ± 3.421 (cells/mm2 ) at T0 to 4.815 ± 1.511 cells/mm2 at T1 (p = .0173). CD8 expression values decreased from 4.360 ± 3.421 (cells/mm2 ) to 2.753 ± 1.451 (cell/mm2 ) at T1 (p = .0003). Monocyte/macrophage marker CD68 varied from 8.208 ± 2.314 (cells/mm2 ) at T0 to 7.600 ± 1876 (cells/mm2 ) at T1 (p = .0003). CONCLUSION: VLNT decreases skin and subcutaneous tissues' infiltration of inflammatory cells, providing one explanation for the positive control of lymph node transfer procedure over infectious and immune-mediated processes.

Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM197 conjugate vaccine.

Polysaccharide-protein conjugates have been developed to overcome the T-independent response, hyporesponsiveness to repeated vaccination, and poor immunogenicity in infants of polysaccharides. To address the impact of polysaccharide length, typhoid conjugates made with short- and long-chain fractions of Vi polysaccharide with average sizes of 9.5, 22.8, 42.7, 82.0, and 165 kDa were compared. Long-chain-conjugated Vi (165 kDa) induced a response in both wild-type and T cell-deficient mice, suggesting that it maintains a T-independent response. In marked contrast, short-chain Vi (9.5 to 42.7 kDa) conjugates induced a response in wild-type mice but not in T cell-deficient mice, suggesting that the response is dependent on T cell help. Mechanistically, this was explained in neonatal mice, in which long-chain, but not short-chain, Vi conjugate induced late apoptosis of Vi-specific B cells in spleen and early depletion of Vi-specific B cells in bone marrow, resulting in hyporesponsiveness and lack of long-term persistence of Vi-specific IgG in serum and IgG+ antibody-secreting cells in bone marrow. We conclude that while conjugation of long-chain Vi generates T-dependent antigens, the conjugates also retain T-independent properties, leading to detrimental effects on immune responses. The data reported here may explain some inconsistencies observed in clinical trials and help guide the design of effective conjugate vaccines.

The medial sural artery perforator flap for retromolar trigone reconstruction: A multicenter case series.

BACKGROUND: Retromolar trigone (RMT) cancer is a rare malignancy, which develops in a narrow area of the oral cavity. Surgical intervention requires wide excision and appropriate reconstruction usually with a free tissue transfer. Little has been published regarding the ideal microvascular reconstruction, mainly focusing on radial forearm and anterolateral thigh free flap. The medial sural artery perforator flap (MSAP) is not new for head and neck reconstruction but its use for RMT reconstruction has not been previously explored. The purpose of the study is to present a multicentric case series investigating the reliability of MSAP flap for RMT reconstruction. METHODS: The study is designed as a retrospective case series. All patients diagnosed with RMT cancer and undergone surgical resection and immediate reconstruction with a MSAP flap between February 2016 and March 2020 were identified. Patients' demographics and surgical details were collected. Functional results were evaluated using the Head and Neck Module of the European Organization for Research and Treatment of Cancer at 12 months of follow-up. A total of 34 patients with a mean age of 58 years were included in the study. An average defect size of 31.5 cm2 was observed after RMT tumor resection. RESULTS: The MSAP flaps' average dimensions were 11 ± 3.1 cm in length and 4.7 ± 1.6 cm in width with a mean thickness of 1.4 ± 0.8 cm. No flap complications were observed in 28 cases; four patients developed an orocutaneous fistula. One patient needed surgical revision for venous congestion while only one case of flap failure was observed. At 12 months of follow-up, 87% of the patient cohort had normal, understandable speech. No patient experienced complete loss of swallowing. Results of the H&N35 module showed a significative postoperative improvement in mouth soreness, mouth opening and social (p < .05*). No patient complained difficulty in motility at the donor site. CONCLUSIONS: The MSAP flap appears to be appropriate for RMT reconstruction and could be considered the workhorse for small to medium size defect of RTM region. It has a long pedicle of matching caliber and provides adequate tissue volume with minimal donor site morbidity.

"No-back-scar" Latissimus Dorsi Muscle Flap and Tissue Expander: A Valuable Strategy for Secondary Breast Reconstructions.

An overall complication rates for implant-based breast reconstruction (IBBR) have been reported from 29 to 46%, particularly in the setting of adjuvant radiotherapy. Although the majority of the literature describes autologous conversion in such scenario, a microsurgical flap is not always feasible. The aim of the paper is to assess surgical and patient-reported outcomes of breast reconstruction using a Latissimus Dorsi muscle Flap (LDMF), harvested without a back scar, in combination with a tissue expander for a two-staged reconstruction in the setting of a previously failed IBBR. All consecutive patients undergoing a two-stages LDMF IBBR between January 2016 and June 2020 were retrospectively identified. A minimal length vertical incision along the posterior axillary line was used for LD flap harvest. Demographic, clinical and surgical data were collected. Aesthetic outcome was evaluated with the Aesthetic Item Scale, and BREAST-Q was used to assess patients' reported outcomes. Twenty-one patients met the inclusion criteria. Mean age was 45.6 years, and the average follow-up was 41.2 months after tissue expander replacement with definitive implant. All patients completed the secondary reconstructive procedure, without major complications both at reconstructive and donor flap site. All women reported to be very satisfied with the final breast reconstruction. Second-attempt implant-based breast reconstruction for patients with a previously failed IBBR is challenging. A conversion from prosthetic to a mixed breast reconstruction with a "no-back scar" LD flap and tissue expander can be considered as a valuable strategy, especially when an abdominal-based autologous breast reconstruction is not feasible or refused by the patients.Level of Evidence IV 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 .

Sewer networks monitoring through a topological backtracking.

The interest in wastewater monitoring is always growing, with applications mainly aimed at detection of pollutants and at the environmental epidemiological surveillance. However, it often happens that the strategies proposed to manage these problems are inapplicable due to the lack of information on the hydraulics of the systems. To overcome this problem, the present paper develops and proposes a topological backtracking strategy for the optimal monitoring of sewer networks, which acts by subrogating the hydraulic information with the geometric ones, e.g., diameter and slope, thus not requiring any hydraulic simulation. The topological backtracking approach aims at evaluating an impact coefficient for each node of the network used to face with the problems of sensor location and network coverage for purposes related to the spread of contaminants and pathogens. Finally, the positioning of the sensors for each monitoring scheme is addressed by a priority rank, based on the efficiency of each sensor in terms of network coverage with respect to a specific weight (e.g., length, flow). The main goal is to design a monitoring scheme that provide the required coverage of the network by minimizing the number of sensors with respect to specific measurement threshold value. The results show the effectiveness of the strategy in supporting the optimal design with the topological-based backtracking approach without the necessity of performing hydraulic simulations, with great advantage in terms of required data and computational time.

Long-Term Chromatic Durability of White Spot Lesions through Employment of Infiltration Resin Treatment.

Background and Objectives: White spot lesions (WSLs) denote regions of subsurface demineralization on the enamel that manifest as opaque and milky-white regions. Treatment for WSLs is essential for both clinical and aesthetic reasons. Resin infiltration has been identified as the most efficacious solution for alleviating WSLs, but studies with long-term monitoring are scarce. The aim of this clinical study is to assess the color change stability of the lesion after four years of implementing the resin infiltration technique. Materials and Methods: Forty non-cavity and unrestored white spot lesions (WSLs) were treated with the resin infiltration technique. The color of the WSLs and adjacent healthy enamel (SAE) was assessed using a spectrophotometer at T0 (baseline), T1 (after treatment), T2 (1 year after) and T3 (4 years after). The Wilcoxon test was utilized to determine the significance of the variation of color (ΔE) between WSLs and SAE over the observed time periods. Results: When comparing the color difference ΔE (WSLs-SAE) at T0-T1, the Wilcoxon test demonstarated a statistically significant difference (p < 0.05). For ΔE (WSLs-SAE) at T1-T2 and T1-T3, the color variation was not statistically significant (p = 0.305 and p = 0.337). Conclusions: The study's findings indicate that the resin infiltration technique is an effective solution for resolving the appearance of WSLs, and the results have demonstrated stability for a minimum of four years.

The role of sentinel node tumor burden in modeling the prognosis of melanoma patients with positive sentinel node biopsy: an Italian melanoma intergroup study (N = 2,086).

BACKGROUND: The management of melanoma patients with metastatic melanoma in the sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients. METHODS: A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed. Overall survival (OS) was the outcome of interest; included independent variables were the following: age, gender, primary melanoma site, Breslow thickness, ulceration, sentinel node tumor burden (SNTB), number of positive SN, non-sentinel lymph nodes (NSN) status. Univariate and multivariate survival analyses were performed using the Cox proportional hazard regression model. RESULTS: The 3-year, 5-year and 10-year OS rates were 79%, 70% and 54%, respectively. At univariate analysis, all variables, except for primary melanoma body site, were found to be statistically significant prognostic factors. Multivariate Cox regression analysis indicated that older age (P < 0.0001), male gender (P = 0.04), increasing Breslow thickness (P < 0.0001), presence of ulceration (P = 0.004), SNTB size (P < 0.0001) and metastatic NSN (P < 0.0001) were independent negative predictors of OS. CONCLUSION: The above results were utilized to build a nomogram in order to ease the practical implementation of our prognostic model, which might improve treatment personalization.

Correlates of adjuvanticity: A review on adjuvants in licensed vaccines.

After decades of slow progress, the last years have seen a rapid acceleration of the development of adjuvanted vaccines which have lately been approved for human use. These adjuvants consist of different components, e.g. aluminium salts, emulsions such as MF59 and AS03, Toll-like receptor (TLR) agonists (CpG ormonophosphoryl lipid A (MPL) adsorbed on aluminium salts as in AS04) or combination of immunopotentiators (QS-21 and MPL in AS01). Despite their distinctive features, most of these adjuvants share some key characteristics. For example, they induce early activation (although at different levels) of innate immunity which then translates into higher antibody and cellular responses to the vaccine antigens. In addition, most of these adjuvants (e.g. MF59, AS03, AS04) clearly induce a wider breadth of adaptive responses able to confer protection against, for example, heterovariants of the influenza viruses (MF59, AS03) or against human papillomavirus strains not contained in the vaccine (AS04). Finally, the use of some of these adjuvants has contributed to significantly enhance the immune response and the efficacy and effectiveness of vaccines in the elderly who experience a waning of the immune responsiveness to infection and vaccination, as shown for MF59- or AS03-adjuvanted influenza vaccines and AS01-adjuvanted herpes zoster vaccine. These results, together with the track record of acceptable safety profiles of the adjuvanted vaccines, pave the way for the development of novel vaccines at the extremes of age and against infections with a high toll of morbidity and mortality. Here, we review the mechanisms associated with the performance of those adjuvanted vaccines in animal models and in humans through recent advances in systems vaccinology and biomarker discovery. We also provide some perspectives on remaining knowledge gaps but also on opportunities that could accelerate the development of new vaccines.

Prevention of Secondary Lymphedema after Complete Lymph Node Dissection in Melanoma Patients: The Role of Preventive Multiple Lymphatic-Venous Anastomosis in Observational Era.

Background and Objectives: Current guidelines have limited the performance of complete lymph node dissection (CLND) for patients with clinically detectable lymphatic metastases. Despite the limitations of this surgical procedure, secondary lymphedema (SL) is an unsolved problem that affects approximately 20% of patients undergoing CLND. Preventive lymphatic-venous micro-anastomoses (PMLVA) has already demonstrated its efficacy in the prevention of SL in melanoma patients with a positive sentinel lymph node biopsy (SLNB), but the efficacy of this procedure is not demonstrated in patients with clinically detectable lymphatic metastases. Materials and Methods: This retrospective cohort study, was performed in two observation periods. Until March 2018, CLND was proposed to all subjects with positive-SLNB andPMLVA was performed in a subgroup of patients with risk factors for SL (Group 1). From April 2018, according to the modification of melanoma guidelines, all patients with detectable metastatic lymph nodes underwent PMLVA during CLND (Group 2). The frequency of lymphedema in subjects undergoing PMLVA was compared with the control group. Results: Database evaluation revealed 172 patients with melanoma of the trunk with follow-up information for at least 6 mounts. Twenty-three patients underwent PMLVA during CLND until March 2018, 29 from April 2018, and 120 subjects underwent CLND without any preventive surgery (control Group). The frequency of SL was significantly lower in both Group 1 (4.3% vs. 24.2%, p = 0.03) and Group 2 (3.5%, p = 0.01). Patients undergoing PMLVA showed a similar recurrence-free periods and overall survival when compared to the control group. Conclusions: PMLVA significantly reduces the frequency of SL both in immediate and delayed CLND. This procedure is safe and does not lead to an increase in length of hospitalization.

The surgical treatment of non-metastatic melanoma in a Clinical National Melanoma Registry Study Group (CNMR): a retrospective cohort quality improvement study to reduce the morbidity rates.

BACKGROUND: Reproducible, high-quality surgery is a key point in the management of cancer patients. Quality indicators for surgical treatment of melanoma has been presented with benchmarks but data on morbidity are still limited. This study presents the quality indicators on morbidity after surgical treatment for non-metastatic skin melanoma in an Italian registry. METHODS: Data were extracted from the Central National Melanoma Registry (CNMR) promoted by the Italian Melanoma Intergroup (IMI). All surgical procedures (WE, SNLB or LFND) for non-metastatic skin melanoma between January 2011 and February 2017 were evaluated for inclusion in the study. Only centers with adequate completeness of information (> 80%) were included in the study. Short-term complications (wound infection, dehiscence, skin graft failure and seroma) were investigated. RESULTS: Wound infection rate was 1.1% (0.4 to 2.7%) in WE, 1.3% (0.7 to 2.5%) in SLNB and 4.1% (2.1 to 8.0%) in LFND. Wound dehiscence rate was 2.0% (0.8 to 5.1%) in WE, 0.9% (0.2 to 3.0%) in SLNB and 2.8% (0.9 to 8.6%) in LFND. Seroma rate was 4.2% (1.5 to 11.1%) in SLNB and 15.1% (4.6 to 39.9%) in LFND. Unreliable information was found on skin graft failure. CONCLUSIONS: Our findings contribute to available literature in setting up the recommended standards for melanoma centers, thus improving the quality of surgery offered to patients. A consensus on the core issues around surgical morbidity is needed to provide practical guidance on morbidity prevention and management.

Local device infection successfully treated without pacemaker removal in a neonate: a case report.

AIMS: Local device infection is a serious complication, especially in neonates. Complete device removal is the gold standard treatment for cardiac device infection; however, in selected cases alternative strategies could be adopted. We describe a case of a 14-day-old neonate, weighing 2.5kg, who had undergone epicardial double chamber pacemaker implantation for a congenital complete atrioventricular block. The generator pocket was created in the epigastric area below the rectus abdominis. At six days after implantation, pocket infection was found; blood cultures and the transoesophageal echocardiogram were normal. Due to the low weight of the neonate, and the limited possibility of finding a new comfortable site for housing the generator far from the infected area, we opted for a conservative strategy. We successfully applied a combination of antibiotic therapy, a vacuum-assisted wound closure system (KCI, Germany) for 40 days, and then skin transfer flap from the right flank without device removal. At one-year follow-up there were no local or systemic signs of infection.

Skin Reducing Mastectomy and Prepectoral Breast Reconstruction in Large Ptotic Breasts.

Large and/or ptotic breasts demonstrate significant difficulty in breast reconstruction and that the rates of perioperative complications are higher compared with the general population. The authors aim to clarify some details on their previously published technique on skin reducing mastectomy and prepectoral ADM breast reconstruction. LEVEL OF EVIDENCE V: 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 .

Investigation of Micro-motion Kinematics of Continuum Robots for Volumetric OCT and OCT-guided Visual Servoing.

Continuum robots (CR) have been recently shown capable of micron-scale motion resolutions. Such motions are achieved through equilibrium modulation using indirect actuation for altering either internal preload forces or changing the cross-sectional stiffness along the length of a continuum robot. Previously reported, but unexplained, turning point behavior is modeled using two approaches. An energy minimization approach is first used to explain the source of this behavior. Subsequently, a kinematic model using internal constraints in multi-backbone CRs is used to replicate this turning point behavior. An approach for modeling the micro-motion differential kinematics is presented using experimental data based on the solution of a system of linear matrix equations. This approach provides a closed-form approximation of the empirical micro-motion kinematics and could be easily used for real-time control. A motivating application of image-based biopsy using 3D optical coherence tomography (OCT) is envisioned and demonstrated in this paper. A system integration for generating OCT volumes by sweeping a custom B-mode OCT probe is presented. Results showing high accuracy in obtaining 3D OCT measurements are shown using a commercial OCT probe. Qualitative results using a miniature probe integrated within the robot are also shown. Finally, closed-loop visual servoing using OCT data is demonstrated for guiding a needle into an agar channel. Results of this paper present what we believe is the first embodiment of a continuum robot capable of micro and macro motion control for 3D OCT imaging. This approach can support the development of new technologies for CRs capable of surgical intervention and micro-motion for ultra-precision tasks.

Precision Medicine and Vaccination of Older Adults: From Reactive to Proactive (A Mini-Review).

As populations age globally, the health of older adults is looming larger on the agendas of public health bodies. In particular, the priority is to ensure that older adults remain healthy, independent, and engaged in their communities. In other words, ensuring that increasing life spans are matched by increasing "health spans," meaning years spent in good health. Chronic conditions such as cancer or respiratory and cardiovascular diseases account for the bulk of the disease burden in older adults, and the consensus is that these can best be tackled by effective primary prevention. However, given the diverse nature of older populations, whose prior health experiences can be complicated by multi-morbidity and poly-pharmacy, effective primary prevention can be challenging. One approach that is gaining momentum is what is called "precision" or P4 medicine. The acronym stands for "predictive, personalized, preventive, participatory" medicine, and is based on the premise that preventing disease is better than treating it. However, effective prevention requires the ability to predict disease risk for a given patient, the tailoring of treatment to their circumstances, and their consent for or participation in the offered treatment. A P4 approach may seem counter-intuitive, given that vaccination is generally considered a public health intervention. However, in this article, we discuss the application of P4 medicine as a complement to planning the vaccination of older individuals, with a special focus on the important role that vaccine-preventable infections play in the burden of non-communicable disease.

Microsurgical reconstruction of the isolated columellar defect with a prelaminated radial forearm free flap. A case report and a review of the literature.

The columella is one of the smallest subunits of the nose, but the loss of this structure has important aesthetic and structural implications. Few papers in literature present microsurgical techniques for the reconstruction of an isolated columellar defect. This report describes the use of a prelaminated radial forearm free flap (RFFF) for the reconstruction of an isolated columellar defect and reviews the current literature. A 45-year-old woman presented to our Unit with a history of palate squamous cell carcinoma and severe nasal deformity with an almost complete loss of the columella. A prelaminated RFFF with the fifth rib was used for a two-staged reconstruction of the isolated columellar defect. The radial pedicle was anastomosed to the facial vessels and the postoperative course was uneventful. Complete survival of the flap was achieved and, 10 months postoperatively, the patient had bilateral nasal patency, with an increased tip projection and a good aesthetic result. A prelaminated RFFF can be considered a valuable reconstructive option in cases of a large composite defect of the columella and limited availability of adjacent tissues.

Microvascular coupler device versus hand-sewn venous anastomosis: A systematic review of the literature and data meta-analysis.

BACKGROUND: Successful vascular anastomosis is essential for the survival of free tissue transfer. The aim of the study is to review the current literature and perform a meta-analysis to assess the potential advantages of a mechanical anastomosis coupler device (MACD) over the hand-sewn (HS) technique for venous anastomoses. METHODS: A systematic Medline search was performed to gather all reports of articles related to MACD from 1984 until now. The following data were extracted: first author and publication date, study design, number of patients and anastomosis, coupler size, site and type of reconstruction, venous anastomotic time, flap failure. A meta-analysis was performed on articles that met the following inclusion criteria: studies comparing MACD and HS technique in venous anastomosis, reporting anastomotic time, and postoperative complications. RESULTS: Thirty-three studies were included for the analysis. Twenty-four were retrospective case series and nine were retrospective comparative studies. A total of 12,304 patients were enrolled with a mean age of 49.23 years (range 31-72). A total of 13,669 flaps were accomplished. The thrombosis rate recorded with MACD was 1.47%. The meta-analysis revealed that MACD significantly decreased anastomotic time (standard difference in means = -0.395 ± 0.105; Z = -3.776; p < .001) and postoperative flap failure risk (odds ratio [OR] = 0.362, 95% confidence interval [CI] = 0.218-0.603, Z = -3.908, p < .001), but it did not decrease postoperative venous thrombosis risk (OR = 0.504, 95% CI = 0.255-1.129, Z = -1.666, p = .096). CONCLUSIONS: MACDs are a safe and effective alternative to traditional anastomosis. The anastomotic coupler is easier, much faster, and requires less technical skills than a HS microvascular anastomosis.

Skin-Reducing Mastectomy and Pre-pectoral Breast Reconstruction in Large Ptotic Breasts.

OBJECTIVES: Pre-pectoral breast reconstruction is increasingly offered to breast cancer patients, as the one-stage technique has proved surgical and oncological safety and aesthetic effectiveness. Nevertheless, there are limited data on outcomes after pre-pectoral breast reconstruction in large and ptotic breasts. The aim of the paper is to present the authors' experience in performing Wise pattern mastectomy with pre-pectoral implant and complete acellular dermal matrix (ADM) coverage as a single-stage procedure in patients with large ptotic breasts. MATERIALS AND METHODS: A retrospective review of protective collected data from January 2017 to June 2019 of patients who presented with large and ptotic breasts undergoing skin-reducing mastectomy and immediate pre-pectoral breast reconstruction with complete ADM coverage and inferior dermal sling was performed. Oncological and surgical outcomes were collected. Satisfaction with reconstruction and related quality of life were evaluated through BREAST-Q questionnaire. RESULTS: Nineteen patients met the inclusion criteria. The average patient age was 55.6 years, and the mean body mass index was 31.2. Mean follow-up was 23.2 months from the initial reconstruction. One patient experienced seroma, and two cases of wound dehiscence at the T junction were observed and treated conservatively with no implant loss. All patients were satisfied with the final reconstruction. CONCLUSION: The Wise pattern skin-reducing mastectomy and pre-pectoral breast reconstruction could be offered to patients presenting with large and ptotic breasts. Future studies should better define long-term outcomes. LEVEL OF EVIDENCE IV: 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.