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1.
Arch Plast Surg ; 51(3): 295-303, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38737838

RESUMO

Background Dupuytren's disease decreases quality of life significantly and often requires surgical treatment, nevertheless there is no actual gold standard. The aim of this study was to introduce the use of minimally invasive pull-through technique. Methods From 2016 to 2020, 52 patients suffering from Dupuytren's contracture were treated with the minimally invasive pull-through technique. We evaluated the improvement in range of motion, pain, disability, and quality of life in the long term. Total extension deficit, quick disabilities of the arm, shoulder, and hand (QuickDASH), and EuroQol five dimensions-five levels index were systematically scored before each surgical intervention and reevaluated after 24 months. Results Fourteen patients (26.9%) had already received a previous intervention (percutaneous needle aponeurotomy or collagenase Clostridium histolyticum ). The mean preoperative total active extension deficit was 84.0 ± 23.3 degrees (55-130 degrees). Mean follow-up was 36 months. There were no cases of tendon rupture or neurovascular injury. Total active extension deficit at the final follow-up was 3.4 ± 2.3 degrees (0-12 degrees). The mean active range of motion of the MCP and PIP joints were, respectively, 90.5 ± 3.3 degrees (85-96 degrees) and 82.7 ± 2.5 degrees (80-87 degrees). At 24 months after cord excision, a mean 10.7 points improvement in the QuickDASH questionnaire was registered ( p < 0.001). Pull-through technique was equally effective both on patients with a primary or a recurrent disease. Eight patients (15.4%) had a recurrence of disease in the metacarpophalangeal joint or proximal interphalangeal joint. Conclusion The pull-through technique is a simple, accessible, and effective technique for the treatment of Dupuytren's contracture. The use of palmar mini-incisions combined with minimal dissection has a low risk of iatrogenic injury to the neurovascular bundles and tendons, and has a low risk of recurrence rate. This study reflects level of evidence IV.

3.
Med Sci Monit ; 30: e942507, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217285

RESUMO

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).


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Adulto Jovem , Fumar/efeitos adversos , Temperatura Alta , Estresse Oxidativo , Lipídeos , Saliva/metabolismo
4.
Microsurgery ; 44(1): e31123, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37788091

RESUMO

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.


Assuntos
Linfedema , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Linfedema/cirurgia , Linfonodos/cirurgia , Extremidades/cirurgia , Abdome
6.
Life (Basel) ; 13(12)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38137866

RESUMO

Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare primary skin cancer, with an annual incidence of 1/100,000 and about 85 cases published in the literature. It is considered the cutaneous counterpart of undifferentiated nasopharyngeal carcinoma (UNC, Schmincke-Regaud tumor) but has no association with EBV. We present an interesting case with features of LELCS in a 93-year-old man, right frontal-orbital region, diagnosed histologically and with immunohistochemical features. We also emphasize contrasting morphologic features for correct nosographic classification and address current issues, suggesting potential insights. Finally, we briefly reviewed other cases described in the literature.

7.
J Environ Manage ; 346: 119015, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37738718

RESUMO

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.

8.
Aesthetic Plast Surg ; 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37605018

RESUMO

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 .

9.
J Clin Med ; 12(14)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37510702

RESUMO

(1) Background: Extravasation injuries in pediatric patients can lead to significant harm if they are not promptly diagnosed and treated. However, evidence-based standardization on extravasation management remains limited, particularly for extensive wound necrosis. This case report presents the management of an 8-week-old premature patient with an extensive extravasation injury involving the right forearm and dorsum of the hand. (2) Methods: The patient was evaluated by a multidisciplinary team in our Neonatal Intensive Care Unit. Surgical intervention involved the debridement of necrotic tissues, followed by temporary coverage with an acellular dermal matrix. Definitive coverage was achieved through Meek micrografting after three weeks. Physical therapy was provided with pre- and post-rehabilitation range of motion assessed using goniometric measurements. Scar quality was evaluated using the Vancouver Scar Scale. (3) Results: The engraftment rate of the Meek micrografts was 93%, with 16 out of 226 micrografts lost. The patient achieved a Vancouver Scar Scale score of 6, indicating a moderate degree of scarring. Significant improvements in elbow, wrist, and finger joint range of motion were observed at a 1-year follow-up. (4) Conclusions: Close observation and heightened awareness of extravasation risks by trained personnel are crucial. Meek micrografting combined with dermal substitute coverage represents an innovative approach to managing extravasation wounds in pediatric patients.

10.
NPJ Vaccines ; 8(1): 100, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443176

RESUMO

The pediatric population receives the majority of vaccines globally, yet there is a paucity of studies on the transcriptional response induced by immunization in this special population. In this study, we performed a systems-level analysis of immune responses to the trivalent inactivated influenza vaccine adjuvanted with MF-59 in children (15-24 months old) and in young, healthy adults. We analyzed transcriptional responses elicited by vaccination in peripheral blood, as well as cellular and antibody responses following primary and booster vaccinations. Our analysis revealed that primary vaccination induced a persistent transcriptional signature of innate immunity; booster vaccination induced a transcriptional signature of an enhanced memory-like innate response, which was consistent with enhanced activation of myeloid cells assessed by flow cytometry. Furthermore, we identified a transcriptional signature of type 1 interferon response post-booster vaccination and at baseline that was correlated with the local reactogenicity to vaccination and defined an early signature that correlated with the hemagglutinin antibody titers. These results highlight an adaptive behavior of the innate immune system in evoking a memory-like response to secondary vaccination and define molecular correlates of reactogenicity and immunogenicity in infants.

11.
Trends Immunol ; 44(6): 424-434, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37137805

RESUMO

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.


Assuntos
COVID-19 , Humanos , Enzima de Conversão de Angiotensina 2/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Evasão da Resposta Imune , Pandemias , Ligação Proteica , SARS-CoV-2/metabolismo
12.
Medicina (Kaunas) ; 59(4)2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37109707

RESUMO

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.


Assuntos
Cárie Dentária , Resinas Sintéticas , Humanos , Cor , Resinas Sintéticas/uso terapêutico , Espectrofotometria , Emprego , Cárie Dentária/terapia
13.
Plast Reconstr Surg ; 152(6): 1359-1364, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37092978

RESUMO

SUMMARY: Achilles tendon rupture represents one of the most common tendon ruptures. Although primary repair remains the treatment of choice, surgical complications, such as secondary rupture and tendon exposure, require salvage procedures. This article aims to present the authors' orthoplastic approach for the functional reconstruction of composite secondary Achilles tendon defects. Seven patients with chronic open-wound and large Achilles tendon defects (Kuwada type IV) underwent one-stage reconstruction between October of 2018 and October of 2020. The size of the average soft-tissue defect was 126.2 cm 2 (range, 86.1 to 175.9 cm 2 ), with a tendon gap of 8.2 cm (range, 7.1 to 10.3 cm). A combined team of orthoplastic surgeons performed the reconstructive procedure, using a turndown gastrocnemius fascial flap and a fascia lata autograft for the tendon reconstruction and a free fasciocutaneous anterolateral thigh flap for soft-tissue coverage (graft and flap). Subjective evaluation and quality-of-life measures were obtained preoperatively and 12 months postoperatively using the American Orthopedic Foot and Ankle Score and 36-Item Short-Form Health Survey questionnaire. Mean follow-up was 18.3 months (range, 12 to 24 months). The flap survival rate was 100%. Overall range of motion of the reconstructed side was 87% of the unaffected side (54 degrees versus 62 degrees). The American Orthopedic Foot and Ankle Score and 36-Item Short-Form Health Survey scores of all patients improved significantly ( P < 0.005) at 12 months of follow-up. A microsurgical approach combined with orthopedic techniques can solve complex cases of Achilles tendon secondary rupture, providing a reconstructed tendon that achieves satisfactory anatomic shape and function. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Tendão do Calcâneo , Retalhos de Tecido Biológico , Lesões dos Tecidos Moles , Traumatismos dos Tendões , Humanos , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/lesões , Lesões dos Tecidos Moles/cirurgia , Traumatismos dos Tendões/cirurgia , Ruptura/cirurgia , Fascia Lata/transplante , Resultado do Tratamento
14.
Plast Reconstr Surg ; 152(5): 904e-912e, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36940155

RESUMO

BACKGROUND: Vascularized lymph node transfer (VLNT) has proven to be a valuable treatment for patients with advanced stages of lymphedema. Although spontaneous neolymphangiogenesis has been advocated to explain the positive effects of VLNT, there is still a lack of supportive biological evidence. The aim of this study was to demonstrate the postoperative formation of new lymphatic vessels using histologic skin sections from the lymphedematous limb. METHODS: Patients with lymphedema of the extremities who had undergone gastroepiploic vascularized lymph node flap surgery between January of 2016 and December of 2018 were identified. Full-thickness 6-mm skin-punch biopsy specimens were obtained from patients at identical sites of the lymphedematous limb during the VLNT surgical procedure (T0) and 1 year later (T1). The histologic samples were immunostained with anti-podoplanin/gp36 antibody. RESULTS: A total of 14 patients with lymph node transfer were included. At the 12-month follow-up, the mean circumference reduction rate was 44.3 ± 4.4 at the above-elbow/above-knee level and 60.9 ± 7 at the below-elbow/below-knee level. Podoplanin expression values were, on average, 7.92 ± 1.77 vessels/mm 2 at T0 and 11.79 ± 3.38 vessels/mm 2 at T1. The difference between preoperative and postoperative values was statistically significant ( P = 0.0008). CONCLUSION: This study provides anatomic evidence that a neolymphangiogenic process is induced by the VLNT procedure because new functional lymphatic vessels can be detected in close proximity to the transferred lymph nodes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Linfonodos , Linfedema , Humanos , Linfedema/cirurgia , Linfedema/etiologia , Sistema Linfático , Extremidade Inferior , Retalhos Cirúrgicos
15.
Microsurgery ; 43(6): 546-554, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36805669

RESUMO

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.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Humanos , Pessoa de Meia-Idade , Retalho Perfurante/irrigação sanguínea , Estudos Retrospectivos , Reprodutibilidade dos Testes , Boca , Artérias
17.
Updates Surg ; 75(1): 235-243, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36401760

RESUMO

Aim of this study is to compare early post-operative outcomes and patient's satisfaction after skin-sparing and/or nipple-sparing mastectomy (SSM/SNSM) followed either by breast reconstruction with one-stage prepectoral implantation or two-stage technique for breast cancer (BC) or BRCA1/2 mutation.From January 2018 to December 2021, 96 patients (mean age of 51.12 ± 10.9) underwent SSM/SNSM and were divided into two groups: in group A (65 patients, 67.7%), mastectomy was followed by one-stage reconstruction; in group B (31 patients, 32.3%) by two-stage. Operative time was significantly longer in A vs. B (307.6 ± 95.7 vs. 254.4 ± 90.91; P < 0.05). Previous breast surgery was more common in B vs. A (29.0% vs. 7.7%; P < 0.05), while bilateral surgery was performed more frequently in A vs. B (40% vs. 6.5%; P = 0.001). All SSM/SNSM for BRCA1/2 mutation were followed by immediate prepectoral implantation. No significant differences were found between groups in terms of post-operative complications. At pathology, DCIS and invasive ST forms, such as multicentric/multifocal forms, were detected more frequently in B, while NST type in A (all P < 0.05). A multivariate analysis showed improved post-operative satisfaction at BREAST-Q survey in Group A (P = 0.001). Encouraging oncologic outcomes after SSM/SNSM for BC enabled the improvement of breast reconstructive techniques. One-stage reconstruction is characterized by better aesthetic outcomes and by greater patient's satisfaction. When SSM/SNSM is technically difficult to perform, as in multicentric/multifocal forms or previous breast surgery, mastectomy followed by two-stage reconstruction should be considered to achieve a radical surgery.


Assuntos
Neoplasias da Mama , Mamoplastia , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Mastectomia/métodos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Satisfação do Paciente , Estudos Retrospectivos , Mamoplastia/métodos
18.
Diagnostics (Basel) ; 12(11)2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36359557

RESUMO

Malignant melanoma (MM) is known to be the great mimic in dermatopathology. Over time, several variants have been described, not all of which have repercussions on the clinical/oncological management of the affected patient. The existence, however, of these alternative forms of MM is of great interest to the pathologist, as they are potentially capable of inducing diagnostic errors affecting the diagnostic-therapeutic care pathway (PDTC). In this paper, we present a very rare case of polymorphic MM, in which five different morphological aspects coexisted in the same lesion, confirmed by immunohistochemical investigation and by RT-PCR for mutation of the BRAF gene and discuss the importance of correct recognition of these different morphological features to avoid misdiagnosis.

19.
Diagnostics (Basel) ; 12(8)2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36010322

RESUMO

The application of artificial intelligence (AI) algorithms in medicine could support diagnostic and prognostic analyses and decision making. In the field of dermatopathology, there have been various papers that have trained algorithms for the recognition of different types of skin lesions, such as basal cell carcinoma (BCC), seborrheic keratosis (SK) and dermal nevus. Furthermore, the difficulty in diagnosing particular melanocytic lesions, such as Spitz nevi and melanoma, considering the grade of interobserver variability among dermatopathologists, has led to an objective difficulty in training machine learning (ML) algorithms to a totally reliable, reportable and repeatable level. In this work we tried to train a fast random forest (FRF) algorithm, typically used for the classification of clusters of pixels in images, to highlight anomalous areas classified as melanoma "defects" following the Allen-Spitz criteria. The adopted image vision diagnostic protocol was structured in the following steps: image acquisition by selecting the best zoom level of the microscope; preliminary selection of an image with a good resolution; preliminary identification of macro-areas of defect in each preselected image; identification of a class of a defect in the selected macro-area; training of the supervised machine learning FRF algorithm by selecting the micro-defect in the macro-area; execution of the FRF algorithm to find an image vision performance indicator; and analysis of the output images by enhancing lesion defects. The precision achieved by the FRF algorithm proved to be appropriate with a discordance of 17% with respect to the dermatopathologist, allowing this type of supervised algorithm to be nominated as a help to the dermatopathologist in the challenging diagnosis of malignant melanoma.

20.
Front Immunol ; 13: 904415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990686

RESUMO

The neonatal immune system is distinct from the immune system of older individuals rendering neonates vulnerable to infections and poor responders to vaccination. Adjuvants can be used as tools to enhance immune responses to co-administered antigens. Antibody (Ab) persistence is mediated by long-lived plasma cells that reside in specialized survival niches in the bone marrow, and transient Ab responses in early life have been associated with decreased survival of plasma cells, possibly due to lack of survival factors. Various cells can secrete these factors and which cells are the main producers is still up for debate, especially in early life where this has not been fully addressed. The receptor BCMA and its ligand APRIL have been shown to be important in the maintenance of plasma cells and Abs. Herein, we assessed age-dependent maturation of a broad range of bone marrow accessory cells and their expression of the survival factors APRIL and IL-6. Furthermore, we performed a comparative analysis of the potential of 5 different adjuvants; LT-K63, mmCT, MF59, IC31 and alum, to enhance expression of survival factors and BCMA following immunization of neonatal mice with tetanus toxoid (TT) vaccine. We found that APRIL expression was reduced in the bone marrow of young mice whereas IL-6 expression was higher. Eosinophils, macrophages, megakaryocytes, monocytes and lymphocytes were important secretors of survival factors in early life but undefined cells also constituted a large fraction of secretors. Immunization and adjuvants enhanced APRIL expression but decreased IL-6 expression in bone marrow cells early after immunization. Furthermore, neonatal immunization with adjuvants enhanced the proportion of plasmablasts and plasma cells that expressed BCMA both in spleen and bone marrow. Enhanced BCMA expression correlated with enhanced vaccine-specific humoral responses, even though the effect of alum on BCMA was less pronounced than those of the other adjuvants at later time points. We propose that low APRIL expression in bone marrow as well as low BCMA expression of plasmablasts/plasma cells in early life together cause transient Ab responses and could represent targets to be triggered by vaccine adjuvants to induce persistent humoral immune responses in this age group.


Assuntos
Vacinas contra a Tuberculose , Tuberculose , Adjuvantes Imunológicos , Adjuvantes Farmacêuticos/metabolismo , Animais , Antígeno de Maturação de Linfócitos B/metabolismo , Medula Óssea , Sobrevivência Celular , Imunidade Humoral , Interleucina-6/metabolismo , Camundongos , Oligodesoxirribonucleotídeos/metabolismo , Plasmócitos , Toxoide Tetânico , Tuberculose/metabolismo
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