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Toll-like receptor 9 (TLR9) agonists have gained traction in recent years as potential adjuvants for the induction of adaptive immune responses. It has nonetheless remained unclear to what extent such ligands can facilitate the priming events that generate antigen-specific effector and/or memory CD8 + T-cell populations. We used an established in vitro model to prime naive precursors from human peripheral blood mononuclear cells in the presence of various adjuvants, including CpG ODN 2006, a synthetic oligonucleotide TLR9 ligand (TLR9L). Unexpectedly, we found that TLR9L induced a suboptimal inflammatory milieu and promoted the antigen-driven expansion and functional maturation of naive CD8 + T cells ineffectively compared with either ssRNA40 or 2'3'-cGAMP, which activate other pattern recognition receptors (PRRs). TLR9L also inhibited the priming efficacy of 2'3'-cGAMP. Collectively, these results suggest that TLR9L is unlikely to be a good candidate for the optimal induction of de novo CD8 + T-cell responses, in contrast to adjuvants that operate via discrete PRRs.

Heart failure (HF) is recognized as a leading cause of morbidity and mortality worldwide. Dilated cardiomyopathy (DCM) is a common phenotype in patients presenting with HF. Timely diagnosis, appropriate identification of the underlying cause, individualized risk stratification, and prediction of clinical response to treatment have improved the prognosis of DCM over the last few decades. In this article, we reviewed the current evidence on available imaging techniques used for DCM patients. In this direction, we evaluated appropriate scenarios for the implementation of echocardiography, nuclear imaging, and cardiac computed tomography, and we focused on the primordial role that cardiac magnetic resonance (CMR) holds in the diagnosis, prognosis, and tailoring of therapeutic options in this population of special clinical interest. We explored the predictive value of CMR toward left ventricular reverse remodeling and prediction of sudden cardiac death, thus guiding the decisions for device therapy. Principles underpinning the use of state-of-the-art CMR techniques such as parametric mapping and feature-tracking strain analysis are also provided, along with expectations for the anticipated future advances in this field. We also attempted to correlate the evidence with clinical practice, with the intent to address questions on selecting the optimal imaging method for different indications and clinical needs. Overall, we recommend a comprehensive assessment of DCM patients at baseline and at follow-up intervals depending on the clinical status, with the addition of CMR as a second-line modality to other imaging techniques. We also provide an algorithm to guide the detailed imaging approach of the patient with DCM. We expect that future guidelines will upgrade their clinical recommendations for the utilization of CMR in DCM, which is expected to further improve the quality of care and the outcomes. This review provides an up-to-date perspective on the imaging of dilated cardiomyopathy patients and will be of clinical value to training doctors and physicians involved in the area of heart failure., (Copyright © 2020 Mitropoulou, Georgiopoulos, Figliozzi, Klettas, Nicoli and Masci.)

Large multicenter studies and meta-analysis have documented the diagnostic accuracy and the prognostic implications of stress echocardiography, cardiac magnetic resonance and, mainly, nuclear stress tests. However, none of them provides a comprehensive anatomical and functional evaluation within the same study as stress CT perfusion. Myocardial CT perfusion is the only non-invasive modality that allows to quantifying coronary stenosis and determining its functional relevance, constituting a potential "one-stop-shop" method for the diagnosis and global management of patients with known or suspected coronary artery disease. In comparison with the dynamic modality, that requires increased radiation, precise acquisition protocols and dedicated post-processing softwares, static CT perfusion was associated with less radiation exposure, non-inferior diagnostic accuracy, easier interpretation of images and is nowadays more widely available., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 Wiley Periodicals, Inc.)

The development of therapeutic strategies to control the reactivation of the Herpes Simplex Virus (HSV) is an unaddressed priority. In this study, we evaluated whether Tat, a HIV-1 protein displaying adjuvant functions, could improve previously established HSV-specific memory responses and prevent viral reactivation. To this aim, mice were infected with non-lethal doses of HSV-1 and, 44 days later, injected or not with Tat. Mice were then monitored to check their health status and measure memory HSV-specific cellular and humoral responses. The appearance of symptoms associated with HSV-reactivation was observed at significantly higher frequencies in the control group than in the Tat-treated mice. In addition, the control animals experienced a time-dependent decrease in HSV-specific Immunoglobulin G (IgG), while the Tat-treated mice maintained antibody titers over time. IgG levels were directly correlated with the number of HSV-specific CD8 + T cells, suggesting an effect of Tat on both arms of the adaptive immunity. Consistent with the maintenance of HSV-specific immune memory, Tat-treated mice showed a better control of HSV-1 re-infection. Although further studies are necessary to assess whether similar effects are observed in other models, these results indicate that Tat exerts a therapeutic effect against latent HSV-1 infection and re-infection by favoring the maintenance of adaptive immunity.

Background: Free ileocolon flap is a reliable technique allowing simultaneous restoration of swallowing and speech. The aim is to report our 6-year experience in a single center., Methods: Thirty-seven patients treated between 2010 and 2015 were included in the study. Swallowing and speech function were evaluated in 27 patients with a 7-point and 5-point Likert scale, respectively. Moreover, 12 of them consented to voice spectrum analysis (VSA)., Results: Complications noted were: aspiration (3), esophagocutaneous fistula (2), and stricture (1). Seven patients experienced self-limited diarrhea. Regarding swallowing function, 77.8% scored ≥5 on Likert scale whereas speech Likert scale showed excellent results (score >12) in 74%. VSA demonstrated mean phonation time of 10.75 seconds, mean frequency of 131 Hz and mean dynamic range of 56 dB., Conclusion: In experienced hands, the ileocolon flap is safe and effective, particularly in patients with long-life expectancy, providing good swallowing and speech function without further procedures/prostheses.

Background: Preoperative localization of the perforators allows precise planning of the flap design and improves surgical efficiency. Recently, infrared thermography is introduced as a reliable alternative, where the perforator corresponds to the "hot spot" on the thermogram. This study aims to compare the application of color Doppler ultrasound (CDU) and infrared thermography in preoperative perforator mapping of the anterolateral thigh (ALT) perforator flap., Patients and Methods: From September 2017 to January 2019, CDU and infrared thermography were both applied on 20 patients to locate the perforators originated from lateral circumflex femoral artery preoperatively. The perforators identified using each modality were marked on the anterolateral thigh region. The accuracy of both mapping methods was analyzed according to the intraoperative findings. The relation between location bias and the thickness of subcutaneous tissue was analyzed., Results: A total of 20 ALT flaps were included. Fifty-three perforators were detected by CDU, and 51 "hot spots" were identified by infrared thermography, in which 50 "hot spots" corresponded to CDU, and the consistency test showed that the κ index was 0.712 (P < 0.05), representing high consistency. The infrared thermography has a sensitivity of 94.3% and a specificity of 85.7% compared with CDU. The deviation between thermal imaging and CDU was positively correlated with the thickness of the subcutaneous tissue. The Pearson correlation coefficient was 0.84 (R = 0.84). Forty-four perforators marked by CDU were selected for designing the flap. Anatomical findings showed that the accuracy rate of CDU and infrared thermal was 93.2% (41 of 44) and 86.3% (38 of 44), respectively. There was no statistical difference (P > 0.05)., Conclusions: Compared with CDU, infrared thermography can be used to locate perforators, in this case, the ALT perforators, with a high degree of consistency. It is portable, economical, noninvasive, and easy to operate. It has higher accuracy in patients with thinner subcutaneous tissue. We believe that infrared thermography can be a useful technique for perforator mapping, especially in patients where the subcutaneous tissue is thinner.

Introduction: Reconstruction of chronic lower extremity wounds can be especially challenging when these wounds are complicated by osteomyelitis. They require the joint expertise of plastic and orthopaedic surgeons., Methods: We report our experience using the Keystone Perforator Island Flap following wound and bone debridement as a valuable surgical tool for coverage of complex wounds with bone infection., Results: Twelve patients underwent similar procedures with overall good outcomes, although two patients experienced a complication, specifically partial flap necrosis and wound dehiscence subsequent to recurrent osteomyelitis. We also reviewed the underlying physiological mechanisms of employing the Keystone flap in order to demonstrate its advantages and efficacy., Conclusion: Our results confirm that the Keystone flap can be a safe, reliable and effective method for coverage of soft tissue defects and the preservation of bone integrity in the management of patients with chronic osteomyelitis., (Copyright © 2019. Published by Elsevier Ltd.)

Aims: Coronary CT angiography (CCTA) is an accurate non-invasive tool for the evaluation of coronary artery bypass graft (CABG). However, inability to sustain a long breath-hold, high heart rate (HR) and atrial fibrillation may affect image quality. Moreover, radiation exposure is still a matter of some concern. A scanner combining 0.23-mm spatial resolution, new iterative reconstruction and fast gantry rotation time has been recently introduced in the clinical field. The aims of our study were to evaluate interpretability, radiation exposure and diagnostic accuracy of CCTA performed with the latest generation of cardiac-CT scanners compared to invasive coronary angiography (ICA) in the assessment of bypass grafts, and non-grafted and post-anastomotic native coronary arteries., Methods and Results: We prospectively enrolled 300 patients undergoing clinically indicated CCTA with a 16-cm z-axis coverage, 256-detector rows, and 0.28-sec gantry rotation time scanner. Coronary artery and graft interpretability, image quality and effective dose (ED) were assessed in all patients and diagnostic accuracy was evaluated in a subgroup of 100 patients who underwent ICA. Mean HR during the scan was 69.6 ± 10.8. Sinus rhythm was present in 118 patients with HR < 75 bpm and in 112 patients with HR ≥ 75 bpm, while 70 patients had atrial fibrillation. CABG interpretability was 100%. Compared to ICA, CCTA was able to correctly detecting occlusions or significant stenoses of all CABG segments. Overall interpretability of native coronary segments was 95.6%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of coronary arteries were 98.3%, 97.4%, 93.1%, 99.3% and 96.5%, respectively. The diagnostic accuracy in a patient based analysis was 95.2%. Mean ED was 3.14 ± 1.7 mSv., Conclusions: The novel whole-heart coverage CT scanner allows to evaluating CABG and native coronary arteries with excellent interpretability and low radiation exposure even in the presence of unfavorable heart rhythm., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

The COVID-19 virus is severely testing the Italian healthcare system, as the requests for intensive treatment are greater than the real capacity of the system to receive patients. Given this emergency situation, it follows that citizens are limited in their freedom of movement in order to limit infection, and that in hospitals a significant number of critical situations must be faced. This brief contribution aims to offer a reflection on the public and clinical role of the bioethicist: a figure able to promote dialogue between the world of medicine and the community, and to face ethical dilemmas even in emergent clinical settings., (Copyright 2020 The Journal of Clinical Ethics. All rights reserved.)

Background: Vascularized lymph node transfer (VLNT) is an emerging surgical treatment for lymphedema. However, literature-comparing outcomes of upper limb lymphedema (ULL) and lower limb lymphedema (LLL) is limited. Hence, the aim of this study is to compare the long-term clinical outcomes on ULL versus LLL in patients treated with VLNT., Methods: A retrospective study retrieving data from patients with International Society of Lymphology (ISL) stages II-III who underwent different VLNTs from July 2010 to July 2016 in our institution was performed. Demographics preoperatively, and clinical data (limb circumference, infectious episodes, lymphoscintigraphic studies) preoperatively and postoperatively were recorded. Clinical outcomes by extremity were also analyzed., Results: A total of 83 patients with lymphedema (ULL: n = 30, LLL: n = 53) were included. Mean follow-up time was 32.8 months (range 24-49 months). Mean circumference reduction was higher in patients with ULL compared to with LLL (28.6 ± 8.6 vs. 22.3 ± 10.1, p < .001), and for patients with secondary lymphedema (24.8 ± 9.6, p < .001) than for patients with primary lymphedema (18.9 ± 14, p > .05). Infectious episodes per year preoperative and postoperative showed that LLL patients had higher reduction on infection rate compared with ULL patients (2.4 ± 1.1 vs. 1.9 ± 1.2, p < .001)., Conclusion: VLNT is a promising surgical treatment option for patients with lymphedema. This study suggests that VLNT may have a more beneficial outcome in patients with ULL and with secondary lymphedema., (© 2019 Wiley Periodicals, Inc.)

Coronary computed tomography angiography (CCTA) is at the frontline of the diagnostic strategies to detect coronary artery disease (CAD). Anatomical information have proven to be insufficient to detect hemodynamic significant epicardial stenosis. In the present invited review we discuss on FFR CT and stress CTP, emerging technologies for an accurate and comprehensive evaluation of patients with suspected CAD, offering both anatomical (i.e. luminal and plaque) and functional assessment in one single technique., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: The emerging role of coronary computed tomography angiography (CCTA) as a non-invasive tool for atherosclerosis evaluation is supported by data reporting a good correlation between CCTA and intravascular ultrasound (IVUS) for plaque volume quantification. Aim of the present study was to evaluate whether a last generation CT-scanner may improve coronary plaque volume assessment using IVUS as standard-of-reference., Methods and Results: From a registry of 1915 consecutive, all-comers, patients who underwent a clinically indicated IVUS evaluation we enrolled 59 patients who underwent CCTA with a 64-slice CT (Group 1) and 59 patients who underwent CCTA with whole-heart coverage CT scanner (Group 2). Patients who underwent CCTA with unfavourable heart rhythm were not excluded from the analysis. Image quality (4-point Likert scale) focused on plaque analysis was evaluated. Plaque volume quantification by CCTA was compared to IVUS. No difference in clinical characteristics was found between Group 1 and Group 2. Plaque volume quantification by CCTA was considered not feasible in 11 plaques of Group 1 and in 4 plaques of Group 2 (P = 0.09). Higher correlation for plaque volume quantification by CCTA vs. IVUS was demonstrated in Group 2 when compared with Group 1 (r = 0.9888 vs. 0.9499; P < 0.0001). The Bland-Altman analysis showed plaque volume overestimation by CCTA of 11.9 mm3 in Group 1 and 4 mm2 in Group 2 (P < 0.001). Effective radiation dose of CCTA was significantly lower in Group 2 vs. Group 1 (2.7 ± 0.9 vs. 8.1 ± 3.6 mSv, respectively; P < 0.001)., Conclusions: CCTA using a new scanner generation showed to be an accurate non-invasive tool to assess and quantify coronary plaque volume., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Skin cancer is the most common malignant cancer with an incidence of 1 million cases/year. It is well known that exposure to UV radiation from sunlight leads the most frequent risk factors for several skin disorders including skin cancer. Sunscreen filters represent a valid protection against dangerous effects derived from UV radiation, and they can be divided in organic and inorganic UV filters. Adding, at the product formulation, molecules with booster effect, or also substances that can increase the protecting effectiveness via synergic mechanisms, can further enhance their protection activity. Moreover, this approach leads to develop formulations with high SPF (Sun Protection Factor) with a reduced content of UV filters, this is in line with the recent decisions of yet a few countries (Palau, Thailand, Philippines, and Hawaii) to ban some sunscreen filters to preserve marine environments (i.e., reef). In this work, a new class of sunscreen UV filters has been synthesized, by means the combination of physical filter and Oxisol, an antioxidant molecule with booster effect. In this study, the synthesis of new physical multifunctional ingredients is reported, by means the direct surface functionalization of inorganic filters (in particular TiO 2 ) with Oxisol. In this study, the full characterization of these multifunctional ingredients is also reported, in addition to the cytotoxicity tests, the photocatalytic activity and the rheological properties involved on skin application., Competing Interests: The authors declare no conflict of interest.

: Human papillomavirus (HPV) persistent infections are associated with cervical cancer and other HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently available HPV vaccines is important. A total of 149 female subjects vaccinated with Cervarix or Gardasil participated to the study and they were stratified according to age (10-12-year-old and 16-20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memory B cells were analyzed after an average of 4-6 years from the third immunization. The humoral responses against HPV-16 and HPV-18 (and HPV-6 and HPV-11 for Gardasil) were high in both age groups and vaccines up to six years from the third dose. However, Cervarix induced significantly higher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memory B cells against HPV-16 and HPV-18. Moreover, the percentage of subjects with vaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individuals with circulating antibodies, but undetectable memory B cells were found. Finally, a higher proportion of Cervarix-vaccinated subjects displayed cross-neutralizing responses against non-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differently affect long-lasting humoral immunity from both the quantitative and qualitative point of view., Competing Interests: The authors declare no conflict of interest.

Introduction: Reconstruction of abdominal wall defects with enterocutaneous fistulas (ECF) remains challenging. The purpose of this report is to describe a single-stage approach using combined microscopic enterolysis, pedicle seromuscular bowel flaps, mesh, fasciocutaneous, and myocutaneous flaps., Methods: Between 1990 and 2016 a retrospective review identified a total of 18 patients with an average age of 39 years (ranging 26-59 years). Thirteen cases were associated with trauma, four were complication of previous mesh repair, and one was after an aortic dissection. Average diameter of defect size was 22 cm (ranging 20-24 cm). Surgical technique involved enterolysis using microscope magnification, a pedicle seromuscular bowel flap to reinforce the bowel anastomosis, mesh, musculocutaneous, and fasciocutaneous flaps to reconstruct the abdominal wall., Results: Fifteen patients required rotational flaps with an average skin paddle area of 442.7 cm 2 (ranging 440 cm 2 -260 cm 2 ) and 10 patients required a serosal patch with an average length of 5 cm (ranging 4-6 cm). Complications included three wound dehiscence and one abdominal wall bulging. Flap survival was 100%. The majority of patients (12 out of 18) were able to resume normal activities, and the remaining (n = 6) were able to resume most activities. Functional outcome as assessed by 36-Item Short Form Survey (SF-36) physical function component questionnaire at 18-24 months follow up was 67.8% (ranging from 59 to 72%). Mean length of hospital stay was 2.2 weeks (ranging 1.4-2.7 weeks). Mean follow-up was 24 months (ranging 22-26 months) with clinical examination., Conclusion: Microscopically assisted intra-abdominal dissection with resection of diseased bowel, replacement with well-vascularized tissue at the anastomosis site in, and reinforcement with mesh combined with pedicle musculocutaneous and fasciocutaneous flaps may be an alternative when other local reconstructive options have failed., (© 2018 Wiley Periodicals, Inc.)

During the Renaissance period, hands were as important a focus of attention as the face was, because they were the only other visible area of the body. Hence, representation of the position of the hands became a decorative element that was almost as important as the face. Thus, given its high visibility, hand gestures in portraits and paintings have been one of the most effective ways of conveying secrets, codes and messages. From the historical and religious perspective, hand signs in visual art may provide clues about the underlying iconographical symbols. This paper will examine the eventual hidden meanings behind a peculiar hand gesture that has been widely used by several painters. (www.actabiomedica.it).

The incidence of skin cancer is increasing both because of climate change and the increase in pollution than people's incorrect habits of sun exposure. In these regards, sunscreen and photoprotection are essential tools in consenting the benefits induced by safe solar light exposition and skin cancer prevention. In this work, a new class of sunscreen filter was synthesized by chemical combination of a physical filter (ZnO) and Oxisol (dihydroxyphenyl benzimidazole carboxylic acid), an antioxidant molecule with booster effect. In this work, a new class of filters with new properties was achieved by direct functionalization of particles surface. A full characterization of this multifunctional ingredient (ZnO-Ox) was conducted: Compared with the simple mixture, the new filter acts as a multifunctional molecule showing a higher Sun Protection Factor (SPF), a better cytotoxic profile (MTT and NRU assay), and anti-acne activity. A strong reduction of photocatalytic activity of ZnO was observed, also improving the safety profile.

Background: Lymphatic filariasis (LF) in advanced stage is a clinically challenging disability resulting in poor quality of life. In advanced stage of filariasis, medical management is seldom effective and few surgical procedures are beneficial. In this study, we assessed clinical efficacy of a surgical technique combining vascularized lymph node transfer (VLNT) and serial excision for patients affected by advanced LF. Patients and Methods: A total of 17 patients with grades 2 and 3 lower limb lymphedema after three consecutive humanitarian missions in India between 2014 and 2018 underwent excision of excessive soft tissue of leg and supraclavicular lymph node flap transferred to dorsum of foot. Recipient vessels were prepared and microanastomosis was performed. Lymphedema was assessed by measuring leg circumferences at different levels, episodes of infectious lymphangitis, and lymphoscintigraphy. Results: A significant decrease of lower limb circumference measurements at all levels was noted postoperatively. Postoperative lymphoscintigraphy revealed reduced lymph stasis. One patient suffered of a seroma on donor site. Six patients had partial loss of skin graft over the flap at recipient site and it was managed by regrafting. Data analysis observed statistically significant reduction in feeling of heaviness ( p  < 0.005) and episodes of acute lymphangitis after surgery. Conclusion: Advanced LF of leg is difficult to manage using traditional medical treatment. The combination of VLNT and surgical excision provided a safe and reliable approach to treat this debilitating disease.

The aim of this paper is to analyze an Intensive Care Unit case that required ethics consultation at a University Hospital in Northern Italy. After the case was resolved, a retrospective ethical analysis was performed by four clinical ethicists who work in different healthcare contexts (Italy, the United States, and Switzerland). Each ethicist used a different method to analyze the case; the four general approaches provide insight into how these ethicists conduct ethics consultations at their respective hospitals. Concluding remarks examine the similarities and differences among the various approaches and offer a reflection concerning the possibility of a shared resolution to the case. The authors' efforts to come to a tentative consensus may serve as an example for professionals working in medical contexts that reflect an increasing pluralism of values. This article aims to respond to some of these concerns by illustrating how different methods in clinical ethics would be used when considering a real case. The goal is not to establish the best model (if there is one) on a theoretical level, but to learn from actual practice in order to see if there are common elements in the different methods, and to validate their pertinence to clinical ethics consultation.

Objective: Minimally invasive direct coronary artery bypass for the left thoracic artery on the left anterior descending artery is a safe and less traumatic surgical technique. We retrospectively evaluated long-term outcomes in a large series of patients undergoing minimally invasive direct coronary artery bypass., Methods: From 1997 to 2016, 1060 patients underwent minimally invasive direct coronary artery bypass: 646 patients (61%) with isolated proximal left anterior descending disease and 414 patients (39%) with multivessel disease as a part of hybrid coronary revascularization or in association with medical therapy. Long-term follow-up, major cardiac and cerebral adverse events, and freedom from angina were analyzed., Results: Mean age of patients was 71 ± 12.5 years, and median European System for Cardiac Operative Risk Evaluation II was 3.2% (interquartile range, 0.6%-7.8%). Postoperative death occurred in 9 patients (0.8%), and perioperative stroke occurred in 3 patients (0.3%). An angiogram or computed tomography scan was performed and was available in patients within 10 years of follow-up (n = 696), demonstrating a 96.8% graft patency rate. At 13.9 ± 5.6 years of follow-up, no surgical reintervention was performed for left thoracic artery on left anterior descending artery graft failure, but 14 patients underwent left anterior descending or left thoracic artery on left anterior descending artery percutaneous coronary intervention. Kaplan-Meier survival curve shows 87.1% at 5 years (95% confidence interval, 81-92.5), 84.3% at 10 years (95% confidence interval, 77.1-91.4), and 79.8% at 15 years (95% confidence interval, 72.2-87.3). Survival freedom from major adverse events was 87.0% (95% confidence interval, 85.9-88.1) at 5 years and 70.5% (95% confidence interval, 66.4-74.6) at 15 years., Conclusions: Minimally invasive direct coronary artery bypass can be safely performed with low postoperative mortality and morbidity with excellent short- and long-term survival and freedom from major adverse events and angina with a reduced surgical invasiveness., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Chronic HCV infection is characterized by several immunological alterations, such as the accumulation of suppressor cells and of hyperactivated T lymphocytes. However, it is unclear whether direct-acting antiviral (DAA)-mediated HCV clearance restores immune dysfunctions. We performed a phenotypic characterization by flow cytometry of different immune cell subsets, including monocytic myeloid-derived suppressor cells (M-MDSCs) and T lymphocytes in 168 patients with persistent HCV infection not treated, under DAA therapies and sustained virological responders. Chronic HCV infection prompted the accumulation of M-MDSCs independently of patient and clinical characteristics, and altered their metabolic properties. HCV RNA was undetectable in the majority of patients just after few weeks of DAA therapy, whereas M-MDSC levels normalized only 6 months after therapy. In addition, HCV infection deeply perturbed the T cell compartment since a re-distribution of memory CD4 + and CD8 + T cells was observed at the expenses of naïve cells, and memory T lymphocytes displayed increased activation. Notably, these features were only partially restored by DAA therapies in the CD4, but not in the CD8, compartment as high immune activation levels persisted in the terminally differentiated memory CD8 + T cells even more than 1 year after sustained virological response. Together, these results suggest that successful DAA therapies do not lead to full immunological reconstitution as fast as viral clearance.

Proteasome activity affects cell cycle progression as well as the immune response, and it is largely recognized as an attractive pharmacological target for potential therapies against several diseases. Herein we present the synthesis of a series of pseudodi/tripeptides bearing at the C-terminal position different α-ketoamide moieties as pharmacophoric units for the interaction with the catalytic threonine residue that sustains the proteolytic action of the proteasome. Among these, we identified the 1-naphthyl derivative 13c as a potent and selective inhibitor of the β5 subunit of the 20S proteasome, exhibiting nanomolar potency in vitro (β5 IC 50 = 7 nM, β1 IC 50 = 60 μM, β2 IC 50 > 100 μM). Furthermore, it significantly inhibited proliferation and induced apoptosis of the human colorectal carcinoma cell line HCT116., Competing Interests: The authors declare no competing financial interest.

DNA self-assembly is a powerful tool to arrange optically active components with high accuracy in a large parallel manner. A facile approach to assemble plasmonic antennas consisting of two metallic nanoparticles (40 nm) with a single colloidal quantum dot positioned at the hot spot is presented here. The design approach is based on DNA complementarity, stoichiometry, and steric hindrance principles. Since no intermediate molecules other than short DNA strands are required, the structures possess a very small gap (≈ 5 nm) which is desired to achieve high Purcell factors and plasmonic enhancement. As a proof-of-concept, the fluorescence emission from antennas assembled with both conventional and ultrasmooth spherical gold particles is measured. An increase in fluorescence is obtained, up to ≈30-fold, compared to quantum dots without antenna., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Lymphedema resulting from breast cancer treatment is a chronic condition that can significantly compromise quality of life. Several works have documented the efficacy of vascularized lymph node flap transfer (VLNT) for the treatment of advanced-stage lymphedema. Given that the axillary scar may contribute to the patient's existing lymphedema, the authors assumed that combining VLNT and scar release with fat graft could be an effective strategy of treatment. The purpose of this study is to compare the efficacy in the reduction of limb circumference and health-related quality of life between a combined strategy, namely, VLN transfer (VLNT) and axillary scar release with fat grafting, and only VLNT for patients affected by postmastectomy upper limb lymphedema. The idea., Materials and Methods: All patients with stage II and III breast cancer-related lymphedema operated between January 2012 and January 2016 were retrospectively identified, and only those treated by combined VLNT and scar release (Group A) or only VLNT (Group B) were included. The outcomes were assessed clinically by limb circumference measurement and radiologically by lymphoscintigraphy. Lymphedema-related quality of life was evaluated preoperatively and at 1 year follow-up through the LYMQOL questionnaire., Results: Thirty-nine patients met inclusion criteria (Group A = 18; Group B = 21). Mean follow-up was 29 months for Group A and 32 months for Group B. Flap survival rate was 100%, with no donor site morbidity in all patients. A statistically significant difference between the circumference reduction rates (RR) at above elbow level was observed at 3 and 6 months of follow-up comparing the two groups (p<0.00001), with higher values in Group A than in Group B. No significant difference was detected comparing RR values at above and below elbow at 12 and 24 months postoperatively. LYMQOL metrics showed significantly better scores (p<0.0001) in all domains at all follow-up appointments in Group A., Conclusions: Patients with postmastectomy upper limb lymphedema can benefit from combined lymph node transfer and axillary scar release with fat graft, as this approach seems to fasten the onset of improvement and to have a positive impact on patients' quality of life., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The medial thigh is a well-hidden area. The two most common flaps from this area are the transverse upper gracilis (TUG) and profunda artery perforator (PAP) flaps. Herein, we explored the applications of combined TUGPAP flap to reconstruct large and complex defects in different regions., Methods: Between November 2015 and May 2017, 28 patients who underwent reconstruction and extensive soft tissue coverage with the TUGPAP flap for the breasts, head and neck, and pelvi-perineal regions were included. The defects size ranged from 22 to 29 × 6-8 cm. All flaps were based on the two pedicles: the medial circumflex femoral artery for TUG flap and the profunda artery perforator for PAP flap. They were each anastomosed to a set of recipient vessels. A "Y"-shaped interposition vein graft (YVG) was used if only one recipient artery was available., Results: The harvested skin paddle had dimensions ranged from 20 to 30 × 6-9 cm and all flaps survived completely. Postoperative complications included one case each of donor and recipient site seroma, and one case of wound dehiscence. They were all successfully managed conservatively. During an average follow-up period of 12.7 months, one patient reported permanent paresthesia in the donor site and another developed hypertrophic scar. All patients were able to resume daily activity without major concerns., Conclusion: The combined TUGPAP flap is a safe, effective, and a good alternative to the common workhorse flaps as it offers the potential for a large skin paddle and decent soft tissue volume with low donor site morbidity in a well-concealed area., (© 2018 Wiley Periodicals, Inc.)

Immediate loading of maxillary denture prostheses in the context of severe bone atrophy is complicated by posterior implant placement, sometimes requiring a complex surgical approach as zygomatic or pterygoid implants. To overcome this complexity, the authors developed an extra-long (20-24 mm) 24-degree angulated platform. It was tested on 33 patients, with 24 patients immediately loaded (72.7%) for a total of 115 implants (46% nasal). All delayed loading implants osseointegrated. Eight bilateral and six unilateral sinus grafts were performed. There were no complications during the follow-up period., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pathogen recognition receptor (PRR) agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. Using an original in vitro approach to prime naive precursors from unfractionated human peripheral blood mononuclear cells, we assessed the influence of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), a ligand for the stimulator of interferon genes (STING), on the induction of antigen-specific CD8+ T cells. We found that 2'3'-cGAMP and 3'3'-cGAMP were especially potent adjuvants in this system, driving the expansion and maturation of functionally replete antigen-specific CD8+ T cells via the induction of type I IFNs. The biological relevance of these findings was confirmed in vivo using two mouse models, in which 2'3'-cGAMP-adjuvanted vaccination elicited protective antitumor or antiviral CD8+ T cell responses. These results identify particular isoforms of cGAMP as effective adjuvants that may find utility in the development of novel immunotherapies and vaccines.

Sandro Botticelli was one of the most renowned artists of the 15th century. He was based in Florence during the flourishing of the Renaissance, a time when anatomical knowledge of ancient times was reclaimed through cadaveric dissection. This report proposes that such knowledge enabled Botticelli to enhance the iconography of his masterpieces, Madonna of the Pomegranate, by incorporating a concealed image of the heart and cardiac anatomy within it., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The amount of time spent in dialysis waiting for a renal transplantation significantly affects its outcome. Hence, the timely planning of patients' transplant evaluation is crucial. According to data from the Nord Italia Transplant program (NITp), the average waiting time between the beginning of dialysis and the admission to the regional transplant waiting list in Lombardy is 20.2 months., Methods: A multicenter cross-sectional study was conducted in order to identify the causes of these delays and find solutions. Two questionnaires were administered to the directors of 47 Nephrology Units and to 106 patients undergoing dialysis in Lombardy respectively, during their first visit for admission to the transplant waiting list., Results: The comparative analysis of the results revealed that both patients (52%) and directors (75%) consider the time required for registering to the waiting list too long. Patients judge information about the transplant to be insufficient, especially regarding the pre-emptive option (63% of patients declare that they had not been informed about this opportunity). Patients report a significantly longer time for the completion of pre-transplantation tests (more than 1 year in 23% of the cases) compared to that indicated by the directors., Conclusions: The study confirmed the necessity of providing better and more timely information to patients regarding the different kidney transplantation options and highlighted the importance of creating target-oriented and dedicated pathways in all hospitals., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Background: End-stage lower extremity lymphedema (LEL) poses a particularly formidable challenge to surgeons as multiple pathological processes are at work. Because single modality treatment is often unsuccessful, we devised a comprehensive multimodal surgical treatment. The aim of this study is to share the technical considerations and examine the clinical outcomes of this combined approach., Methods: Between 2013 and 2017, patients with International Society of Lymphology stage III, who underwent the combination treatment of Charles,' Homan's procedure with toe management and vascularized lymph node transfer (CHAHOVA), were included in this retrospective study. Outcomes evaluated were limb size, number of infectious episodes, compression garment usage, and rate of complications., Results: A total of 68 patients were included. With a mean follow-up of 29 months, the overall circumference reduction rate for the upper thigh and the rest of the extremity was 67.4% (48.2-88.2%) and 98.1% (88-100%), respectively. During the follow-ups, 2 (2.9%) patients experienced episodes of cellulitis and the average number of yearly infections decreased from 4.2 to 1.2 episodes per person. All patients were able to discontinue compression therapy without recurrence of lymphedema. Nine (13.2%) patients reported minor complications., Conclusion: The combine CHAHOVA in a single-stage procedure is an effective and safe approach in the end-stage LEL., (© 2019 Wiley Periodicals, Inc.)

Introduction: Composite and large head and neck defects requiring extensive skin-mucosa coverage are often reconstructed by combining flaps. Herein, we present a simple and reliable two-stage fibula osteocutaneous (FOC) flap technique to improve the survival of a large skin paddle for oromandibular reconstructions., Methods: From October 2011 to September 2016, 47 patients with through-and-through oromandibular defects were reconstructed using FOC flaps with large skin paddles. To ensure optimum survival of skin paddles, temporary orocutaneous fistula were left in place and closed during the second stage operation via de-epithelialization of the skin paddle and suturing of mucosa. Demographic data, operative details, and postoperative complications were recorded., Results: The skin paddle dimensions ranged from 20 to 31.5 cm in length and 12 to 17 cm in width with an average area of 430.4 cm 2 (range 300-504). The average time between the two stages and hospital stay were 10 days and 14 days, respectively. Complications at the donor site included wound dehiscence (n = 3, 6.4%), partial skin graft loss (n = 3, 6.4%) and hematoma (n = 2, 4.3%). Recipient site complications included two (4.3%) early postoperative venous congestions that resolved after elevation and three (6.4%) partial skin flap necrosis (less than 5% surface area). All complications resolved with bedside conservative management. There was only one take-back for evacuation of recipient site hematoma (2.1%) but no flap loss., Conclusion: Two-staged large skin paddle FOC flaps can simplify reconstruction of extensive oromandibular defects by improving the reliability of the sizable skin paddle and negating the need for a second flap., (© 2018 Wiley Periodicals, Inc.)

Background: Keloids are the result of abnormal wound healing and often are subject to infections and recurrent inflammation. We present a study conducted with a 1470 nm diode laser using an intralesional optical fiber device for the treatment of inflamed keloid scars. We evaluate its efficacy as a novel alternative method to decrease keloid infection and inflammation., Methods: The patients who underwent 1470 nm laser treatment from February 2016 to February 2018 at the plastic and reconstructive surgery department of the Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University with keloid accompanying serious local infection and fester were included. Patients took curative effect evaluation before and 1 year after the treatment. The test items included infection frequency in each year; pain, by visual analogue scale (VAS); itch, using VAS; quality of life (QOL), using QOL scale; and blood supply, using PeriCam PSI., Results: A total of 19 patients (mean age 35.21 years, range 11-66) with history of inflamed keloids with episodes of infection or abscess were enrolled. Patients underwent to a 1470 nm laser therapy for average of 1.16 times. After treatment, infection frequency and blood supply in keloids were reduced ( p  < 0.001). Pain, itching, and QOL were improved ( p  < 0.001)., Conclusion: The present study shows that 1470 nm fiber laser treatment could improve inflamed keloids fairly well by decreasing inflammation, and a relative stabilization of collagen composition. Therefore, it is an effective minimally invasive scar therapy, but further studies are essential to confirm the present results., Competing Interests: The study was conducted in accordance with the guidelines of the Declaration of Helsinki stated in 1964. The study protocol was agreed by the local ethics committee of the Jiao Tong University-Ninth People’s Hospital of Shanghai. Every patient signed written informed consent.All presentations of case reports in this article have consent for publication.The authors declare that they have no competing interests.

Lower eyelid malposition is the most frequent and severe complication after blepharoplasty and ectropion is observed in 1% of patients after surgery. This article describes a non-surgical method to treat lower eyelid cicatricial ectropion using a non-ablative laser as an alternative to surgery. Twelve patients with unilateral or bilateral lower lid cicatricial ectropion, following surgery or trauma, underwent laser therapy from 2012 to 2016. Laser therapy was performed with a fractional non-ablative laser emitting at a wavelength of 1540 nm. Ten patients had a full correction of their ectropion and two patients had a partial recovery after laser therapy at 6-month follow-up visit. No serious adverse events were reported. Non-ablative fractional laser resurfacing can successfully treat cicatricial ectropion by remodeling the periocular scar tissue and improving the scar texture, and as such may be considered as a valuable alternative to surgery in selected patients.

The present article analyses eleven paintings of Bronzino, one of the major painters of the late Italian Mannerism, in which the sitters are portrayed with deviating eyes. The reasons why Bronzino may have included a truant eye in his subjects are herein discussed. We consider the 'wandering' eye as a hallmark of Bronzino's style. The inclusion of strabismus may be part of the Mannerism tendency of using exaggerated hallmarks but pursuing at the same time an increasing realism that was typical of the 15th and 16th century movements.

Background: Life-saving technologies have completely changed the normal conception of medical treatments. Left Ventricular Assist Devices (LVAD) can prolong survival for patients who are not candidates for heart transplantation. In order to analyze the pre-implantation phase, which involves a shared-decision making process before activation of the device, attention should be paid to the criterion of "proportionality" in order to properly assess the risks and benefits of implantation., Aim: The aim of our analysis is to provide an useful tool for the assessment of LVAD proportionality during the physicians' decision making., Methods: The method of the "four boxes", developed by Jonsen et al, was chosen to analyze the notion of proportionality and the other main ethical issues regarding LVAD activation in adult patients., Results: Medical issues are not the sole factors, which influence the choice of implantation by patients. Indeed, patient preferences, his/her quality of life, and contextual features should be taken into consideration when proposing LVADs: these factors are as important as clinical issues where outcomes are concerned., Conclusions: In order to assess the proportionality of such a device, we present, discuss and examine, in the framework of the pre-implant phase, the content of each topic treated by the "four boxes method", that is, an essential tool for the assessment of the proportionality of the treatment for LVAD candidates.

The possibility to determine death based on cardiocirculatory criteria in controlled cases, namely when there is a request to withhold treatment-or, more frequently, withdraw it-specifically recalls the recent Italian law on advance treatment directives and leaves the following question unanswered: Under what conditions is the patient's request legally and ethically acceptable? We present three ethical proportionality criteria for supporting physicians' decision-making facing patients' requests of treatment withdrawal, namely: 1. irreversible pathology with an ominous and worsening prognosis; 2. within an evaluation considering both clinical data and the patient's history; and 3. facing burdens that are no longer bearable. We finally argue that reflection over controlled donor may be a model for giving medicine the chance to responsibly deal with broader end-of-life issues., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Characterization of the intracellular biochemical processes that regulate the generation and maintenance of effector and memory CD8 + T-cells from naïve precursors is essential for our understanding of adaptive immune responses and the development of immunotherapies. However, the metabolic determinants of antigen-driven activation and differentiation remain poorly defined, especially in humans. Methods: We used a variety of different approaches, including gene expression profiling and measurements of nutrient flux, to characterize the basal and activation-induced energetic requirements of naïve and phenotypically-defined subsets of human memory CD8 + T-cells. Findings: Profound metabolic differences were apparent as a function of differentiation status, both at rest and in response to stimulation via the T cell receptor (TCR). Of particular note, resting naïve CD8 + T cells were largely quiescent, but rapidly upregulated diverse energetic pathways after ligation of surface-expressed TCRs. Moreover, autophagy and the mechanistic target of rapamycin (mTOR)-dependent glycolytic pathway were identified as critical mediators of antigen-driven priming in the naïve CD8 + T cell pool, the efficiency of which was dampened by the presence of neutral lipids and fatty acids. Interpretation: These observations provide a metabolic roadmap of the CD8 + T-cell compartment in humans and reveal potentially selective targets for novel immunotherapies.

Background: Recent advances in wearable technology make continuous cardiorespiratory monitoring possible, with potential applications in assessment of cardiopulmonary patients, healthy subjects and athletes. The aim of the present study was to qualitatively and quantitatively evaluate a new wearable device (Learn Inspire Free Entertain = L.I.F.E.) by embedding in a compression shirt a 12‑lead ECG system and 5 respiratory sensors., Methods: Thirty cardiorespiratory patients and ten healthy subjects were studied for 24 h during their usual life activities. In 8 healthy subjects, simultaneous measurements of the device and of an ergo-spirometer were performed during different levels of ventilation in five different body positions. The quality of ECG signals in terms of measurability of heart rate, P wave, QRS complex and ST segment, was analyzed by four expert cardiologists/respiratory physiologists using an arbitrary 1-5 scale. The sum of the respiratory signals was used to calculate the respiratory rate, inspiratory time and relative changes of tidal volume. These parameters were compared to ergo-spirometer measurements., Results: Median quality value was >3 for heart rate, QRS complex, ST segment and P wave (except in L3, aVL, aVF, V1 and V2 leads). Median quality of respiratory traces was >4 in patients and between 3 and 4 in healthy subjects. The respiratory monitoring of respiratory rate and inspiratory time was accurate in all body positions. Tidal volumes were underestimated due to a high level of ventilation., Conclusions: The L.I.F.E. device provides an accurate continuous monitoring of cardiorespiratory signals during the 24 h both in normal subjects and cardiorespiratory patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cytotoxic CD8 + T-cells are key players of the immune responses against viruses. During the priming of a CD8 + T-cell response, the activation of a naïve T-cell by a professional antigen presenting cell (APC) involves the induction of various intracellular and metabolic pathways. The modulation of these pathways at the level of APCs or T-cells offers great potential to enhance the induction of robust effector cells and the generation of long-lived memory cells. On the one hand, signaling through pathogen recognition receptors (PRRs) expressed by APCs can greatly influence T-cell priming, and the potential of several PRR ligands as adjuvants are being studied. On the other hand, the engagement of several metabolic processes, at play in APCs and T-cells upon stimulation, implies that modulating cellular metabolism can impact on priming efficacy. Here, we review recent efforts to understand the interplay between PRR mediated signaling and metabolic pathway modulation in this context, through three examples: interplay between TLR4 and fatty acid metabolism, between TLR9 and IDO, and between STING and autophagy. These initial works highlight the potential for harnessing the induction of antiviral CD8 + T-cell responses using synergistic modulation of metabolic and PRR pathways.

Detecting small sequences of RNA in biological samples such as microRNA or viral RNA demands highly sensitive and specific methods. Here, a reconfigurable DNA origami template has been used where a chiral arrangement of gold nanorods on the structure can lead to the generation of strong circular dichroism (CD). Switching of the cross-like DNA structure is achieved by the addition of nucleic acid sequences, which arrests the structure in one of the possible chiral states by specific molecular recognition. A specific sequence can thus be detected through the resulting changes in the plasmonic CD spectrum. We show the sensitive and selective detection of a target RNA sequence from the hepatitis C virus genome. The RNA binds to a complementary sequence that is part of the lock mechanism, which leads to the formation of a defined state of the plasmonic system with a distinct optical response. With this approach, we were able to detect this specific RNA sequence at concentrations as low as 100 pm., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vascularized lymph node transfer has demonstrated promising results for the treatment of extremity lymphedema. In an attempt to find the ideal donor site, several vascularized lymph nodes have been described. Each has a common goal of decreasing morbidity and avoiding iatrogenic lymphedema while obtaining good clinical results. Herein, we present the preliminary clinical outcomes of an intra-abdominal lymph node flap option based on the appendicular artery and vein used for the treatment of extremity lymphedema. A 62 year-old woman with moderate lower extremity lymphedema, on chronic antibiotics because of recurrent infections and unsatisfactory outcomes after conservative treatment underwent a vascularized appendicular lymph node (VALN) transfer. At a follow-up of 6 months, the reduction rate of the limb circumference was 17.4%, 15.1%, 12.0% and 9% above the knee, below the knee, above the ankle and foot respectively. In addition, no further episodes of infection or other complications were reported after VALN transfer. Postoperative lymphoscintigraphy demonstrated that the VALN flap was able to improve the lymphatic drainage of the affected limb. According to our findings, the use of VALN transfer minimizes donor-site morbidity, avoids iatrogenic lymphedema and may provide a strong clearance of infection because of the strong immunologic properties of the appendiceal lymphatic tissue in selected patients. Despite these promising results, further research with larger number of patients and longer follow- up is needed., (© 2016 Wiley Periodicals, Inc.)

Introduction: There is an increased need for evidence-based practices in male-to-female (MtF) transgender vaginoplasty. Although there are a multitude of surgical techniques, there is a paucity of data comparing these procedures. A systematic review of retrospective studies on the outcomes of MtF vaginoplasty was conducted to minimize surgical complications and improve patient outcomes for transgender patients., Methods: Applying the Preferred Reporting Items for Systematic Review and Meta-Analysis, a comprehensive search of several databases from 1985 to November 7, 2017, was conducted. The databases included PubMed, Ovid MEDLINE Epub Ahead of Print, Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Web of Science. The resulting publications were screened, and those that met our specified inclusion/exclusion criteria were analyzed. The DerSimonian and Laird random-effects model was used to pool complications and patient-reported outcomes., Results: A total of 471 articles were initially identified, of which 46 met our eligibility criteria. A total of 3716 cases were analyzed. Overall incidence of complications included the following: 2% (1%-6%) fistula, 14% (10%-18%) stenosis and strictures, and 1% (0%-6%) tissue necrosis, and 4% (2%-10%) prolapse (upper and lower limits of the 95% confidence interval). Patient-reported outcomes included a satisfaction rate of 93% (79%-100%) with overall results, 87% (75%-96%) with functional outcomes, and 90% (79%-98%) with esthetic outcomes. Ability to have orgasm was reported in 70% (54%-84%) of patients. The regret rate was 1% (0%-3%). The length of the vaginal cavity was 12.5 cm (6.3-4.4 cm)., Conclusions: Multiple surgical techniques have demonstrated safe and reliable means of MtF vaginoplasty with low overall complication rates and with a significant improvement in the patient's quality of life. Studies using different techniques in a similar population and standardized patient-reported outcomes are required to further analyze outcomes among the different procedures and to establish best-practice guidelines.

Vascularized lymph node transfer is a quite innovative physiological surgical procedure for the lymphedema treatment. Although is gaining more popularity due to its promising results, there are some concerns regarding difficult to harvest it and the potential risk of iatrogenic lymphedema. Here, we present alternative vascular constructs of lymph node flap for the treatment of lymphedema, which provide the benefits of a technically easier dissection and physiological reconstruction of the damaged lymphatics. Furthermore, we introduce a classification based on the flap vascular supply including six types of flaps and we provide the details of the surgical technique., (© 2018 Wiley Periodicals, Inc.)

Objective: HIV infection is characterized by several immune dysfunctions, such as chronic activation of the immune system, premature aging and loss of CD4 T cells, in particular within the naïve compartment. The Tat protein of HIV is released extracellularly and enters neighboring cells affecting their functionality, for instance impacting on CD8 T-cell programs and activity. As the presence and/or induction of anti-Tat immune responses is associated with reduced T-cell dysfunction and CD4 T-cell loss, we investigated whether Tat impacts human resting or activated CD4 T cells., Methods: Purified CD4 T cells were activated by T cell receptor engagement in the presence or absence of Tat. Cytokine production, surface phenotype and expression of transcription factors important for T-cell programing were measured. Purified naïve CD4 T cells were cultured in nonpolarizing conditions in the presence or absence of Tat and their proliferation and differentiation was evaluated., Results: Tat favors the secretion of IL2, IFNγ and TNFα in CD4 T cells, as well as the upregulation of T-bet and Eomes expression. Naïve CD4 T cells cultured in the presence of Tat showed enhanced expansion and differentiation toward memory phenotype, showing in particular recruitment into the effector memory T-cell pool., Conclusion: Tat affects the programing and functionality of CD4 T lymphocytes favoring the differentiation of naïve CD4 T cells.