RESUMO
Many community- and hospital-acquired bacterial infections are caused by antibiotic-resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) predisposes humans to invasive infections that are difficult to eradicate. We designed a closed-loop gene network programming mammalian cells to autonomously detect and eliminate bacterial infections. The genetic circuit contains human Toll-like receptors as the bacterial sensor and a synthetic promoter driving reversible and adjustable expression of lysostaphin, a bacteriolytic enzyme highly lethal to S. aureus. Immunomimetic designer cells harboring this genetic circuit exhibited fast and robust sense-and-destroy kinetics against live staphylococci. When tested in a foreign-body infection model in mice, microencapsulated cell implants prevented planktonic MRSA infection and reduced MRSA biofilm formation by 91%. Notably, this system achieved a 100% cure rate of acute MRSA infections, whereas conventional vancomycin treatment failed. These results suggest that immunomimetic designer cells could offer a therapeutic approach for early detection, prevention, and cure of pathogenic infections in the post-antibiotic era.
Assuntos
Biomimética/métodos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Infecções Estafilocócicas/prevenção & controle , Fosfatase Alcalina/sangue , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Feminino , Células HEK293 , Humanos , Receptores de Lipopolissacarídeos/genética , Lisostafina/metabolismo , Lisostafina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Plasmídeos/genética , Plasmídeos/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/veterinária , Receptor 1 Toll-Like/genética , Receptor 2 Toll-Like/genética , Receptor 6 Toll-Like/genética , Fator de Transcrição AP-1/metabolismoRESUMO
The cochlear implant (CI) is considered the most successful neuroprosthesis as it enables speech comprehension in the majority of the million otherwise deaf patients. In hearing by electrical stimulation of the auditory nerve, the broad spread of current from each electrode acts as a bottleneck that limits the transfer of sound frequency information. Hence, there remains a major unmet medical need for improving the quality of hearing with CIs. Recently, optogenetic stimulation of the cochlea has been suggested as an alternative approach for hearing restoration. Cochlear optogenetics promises to transfer more sound frequency information, hence improving hearing, as light can conveniently be confined in space to activate the auditory nerve within smaller tonotopic ranges. In this review, we discuss the latest experimental and technological developments of optogenetic hearing restoration and outline remaining challenges en route to clinical translation.
Assuntos
Implantes Cocleares , Optogenética , Optogenética/métodos , Humanos , Animais , Perda Auditiva/fisiopatologia , Audição/fisiologia , Cóclea/fisiologiaRESUMO
Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects-including peri-implant toxicity, aseptic loosening, and pseudotumor-as well as systemic toxic effects-including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo (t1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint.
Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Prótese de Quadril/efeitos adversos , Ácido Hialurônico , Dimercaprol , Terapia por Quelação , Falha de Prótese , Artroplastia de Quadril/efeitos adversos , Metais , Cobalto , Quelantes/uso terapêutico , ÍonsRESUMO
Hearing is critical to spoken language, cognitive, and social development. Little is known about how early auditory experiences impact the brain structure of children with bilateral sensorineural hearing loss. This study examined the influence of hearing aid use and residual hearing on the auditory cortex of children with severe to profound congenital sensorineural hearing loss. We evaluated cortical preservation in 103 young pediatric cochlear implant candidates (55 females and 48 males) by comparing their multivoxel pattern similarity of auditory cortical structure with that of 78 age-matched children with typical hearing. The results demonstrated that early-stage hearing aid use preserved the auditory cortex of children with bilateral congenital sensorineural hearing loss. Children with less residual hearing experienced a more pronounced advantage from hearing aid use. However, this beneficial effect gradually diminished after 17 months of hearing aid use. These findings support timely fitting of hearing aids in conjunction with early implantation to take advantage of neural preservation to maximize auditory and spoken language development.
Assuntos
Córtex Auditivo , Auxiliares de Audição , Perda Auditiva Neurossensorial , Feminino , Masculino , Humanos , Criança , Perda Auditiva Neurossensorial/terapia , Audição , EncéfaloRESUMO
The onset of hearing loss can lead to altered brain structure and functions. However, hearing restoration may also result in distinct cortical reorganization. A differential pattern of functional remodeling was observed between post- and prelingual cochlear implant users, but it remains unclear how these speech processing networks are reorganized after cochlear implantation. To explore the impact of language acquisition and hearing restoration on speech perception in cochlear implant users, we conducted assessments of brain activation, functional connectivity, and graph theory-based analysis using functional near-infrared spectroscopy. We examined the effects of speech-in-noise stimuli on three groups: postlingual cochlear implant users (n = 12), prelingual cochlear implant users (n = 10), and age-matched individuals with hearing controls (HC) (n = 22). The activation of auditory-related areas in cochlear implant users showed a lower response compared with the HC group. Wernicke's area and Broca's area demonstrated differences network attributes in speech processing networks in post- and prelingual cochlear implant users. In addition, cochlear implant users maintain a high efficiency of the speech processing network to process speech information. Taken together, our results characterize the speech processing networks, in varying noise environments, in post- and prelingual cochlear implant users and provide new insights for theories of how implantation modes impact remodeling of the speech processing functional networks.
Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Percepção da Fala , Humanos , Fala , Surdez/cirurgia , Audição , Percepção da Fala/fisiologiaRESUMO
Liquid-transmission electron microscopy (liquid-TEM) provides exciting potential for capturing mineralization events at biomaterial interfaces, though it is largely unexplored. To address this, we established a unique approach to visualize calcium phosphate (CaP)-titanium (Ti) interfacial mineralization events by combining the nanofabrication of Ti lamellae by focused ion beam with in situ liquid-TEM. Multiphasic CaP particles were observed to nucleate, adhere, and form different assemblies onto and adjacent to Ti lamellae. Here, we discuss new approaches for exploring the interaction between biomaterials and liquids at the nanoscale. Driving this technology is crucial for understanding and controlling biomineralization to improve implant osseointegration and direct new pathways for mineralized tissue disease treatment in the future.
Assuntos
Materiais Biocompatíveis , Fosfatos de Cálcio , Microscopia Eletrônica de Transmissão , Titânio , Titânio/química , Materiais Biocompatíveis/química , Fosfatos de Cálcio/química , Microscopia Eletrônica de Transmissão/métodos , Propriedades de Superfície , Osseointegração , HumanosRESUMO
Owing to the presence of microbial biofilm on the implant, the eradication of biofilm-associated infections poses a challenge for antibiotic therapies. The study aimed to investigate the efficacy and safety of the novel antibiotic agent TNP-2092 in the context of implant infections. In vivo, rats with periprosthetic joint infection (PJI) treated with antibiotics showed an increase in body weight and decrease in swelling, temperature, and width of knee, compared with the control group. Meanwhile, inflammatory markers in synovium and serum were decreased in the TNP-2092 group, consistent with the pathological results. Moreover, TNP-2092 was effective in eliminating bacteria and disruption biofilm formation, and further alleviated the abnormal bone absorption and reactive bone changes around the prosthesis. In conclusion, intra-articular injection of TNP-2092 is safe and effective in treating knee PJI in a rat model. The study provides a foundation for the future utilization of TNP-2092 in the management of implant-related infections.
Assuntos
Antibacterianos , Biofilmes , Staphylococcus aureus Resistente à Meticilina , Infecções Relacionadas à Prótese , Infecções Estafilocócicas , Animais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Ratos , Biofilmes/efeitos dos fármacos , Masculino , Injeções Intra-Articulares , Ratos Sprague-Dawley , Modelos Animais de DoençasRESUMO
BACKGROUND: Bone infections from Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to achieve high in situ antibiotic concentrations, which are otherwise challenging to achieve via systemic administration. Existing solutions have been shown to confer suboptimal drug release and distribution. Here we present and evaluate an injectable in situ-forming depot system termed CarboCell. The CarboCell technology provides sustained and tuneable release of local high-dose antibiotics. METHODS: CarboCell formulations of levofloxacin or clindamycin with or without antimicrobial adjuvants cis-2-decenoic acid or cis-11-methyl-2-dodecenoic acid were tested in experimental rodent and porcine implant-associated osteomyelitis models. In the porcine models, debridement and treatment with CarboCell-formulated antibiotics was carried out without systemic antibiotic administration. The bacterial burden was determined by quantitative bacteriology. RESULTS: CarboCell formulations eliminated S. aureus in infected implant rat models. In the translational implant-associated pig model, surgical debridement, and injection of clindamycin-releasing CarboCell formulations resulted in pathogen-free bone tissues and implants in 9/12, and full eradication in 5/12 pigs. CONCLUSIONS: Sustained release of antimicrobial agents mediated by the CarboCell technology demonstrated promising therapeutic efficacy in challenging translational models and may be beneficial in combination with the current standard of care.
RESUMO
Electrical stimulation of retinal ganglion cells (RGCs) with electronic implants provides rudimentary artificial vision to people blinded by retinal degeneration. However, current devices stimulate indiscriminately and therefore cannot reproduce the intricate neural code of the retina. Recent work has demonstrated more precise activation of RGCs using focal electrical stimulation with multielectrode arrays in the peripheral macaque retina, but it is unclear how effective this can be in the central retina, which is required for high-resolution vision. This work probes the neural code and effectiveness of focal epiretinal stimulation in the central macaque retina, using large-scale electrical recording and stimulation ex vivo The functional organization, light response properties, and electrical properties of the major RGC types in the central retina were mostly similar to the peripheral retina, with some notable differences in density, kinetics, linearity, spiking statistics, and correlations. The major RGC types could be distinguished by their intrinsic electrical properties. Electrical stimulation targeting parasol cells revealed similar activation thresholds and reduced axon bundle activation in the central retina, but lower stimulation selectivity. Quantitative evaluation of the potential for image reconstruction from electrically evoked parasol cell signals revealed higher overall expected image quality in the central retina. An exploration of inadvertent midget cell activation suggested that it could contribute high spatial frequency noise to the visual signal carried by parasol cells. These results support the possibility of reproducing high-acuity visual signals in the central retina with an epiretinal implant.SIGNIFICANCE STATEMENT Artificial restoration of vision with retinal implants is a major treatment for blindness. However, present-day implants do not provide high-resolution visual perception, in part because they do not reproduce the natural neural code of the retina. Here, we demonstrate the level of visual signal reproduction that is possible with a future implant by examining how accurately responses to electrical stimulation of parasol retinal ganglion cells can convey visual signals. Although the precision of electrical stimulation in the central retina was diminished relative to the peripheral retina, the quality of expected visual signal reconstruction in parasol cells was greater. These findings suggest that visual signals could be restored with high fidelity in the central retina using a future retinal implant.
Assuntos
Retina , Próteses Visuais , Animais , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Macaca , Próteses e Implantes , Estimulação Elétrica/métodos , Estimulação Luminosa/métodosRESUMO
Total joint arthroplasty is a commonly used surgical procedure in orthopedics. Revision surgeries are required in >10% of patients mainly because of prosthetic joint infection caused by bacteria or aseptic implant loosening caused by chronic inflammation. Encephalitozoon cuniculi is a microsporidium, an obligate intracellular parasite, capable of exploiting migrating proinflammatory immune cells for dissemination within the host. We used molecular detection methods to evaluate the incidence of E. cuniculi among patients who had total hip or knee arthroplasty revision. Out of 49 patients, E. cuniculi genotypes I, II, or III were confirmed in joint samples from 3 men and 2 women who had implant loosening. Understanding the risks associated with the presence of microsporidia in periprosthetic joint infections is essential for proper management of arthroplasty. Furthermore, E. cuniculi should be considered a potential contributing cause of joint inflammation and arthrosis.
Assuntos
Encephalitozoon cuniculi , Encefalitozoonose , Microsporídios , Masculino , Humanos , Feminino , Microsporídios/genética , Encephalitozoon cuniculi/genética , República Tcheca/epidemiologia , Encefalitozoonose/epidemiologia , InflamaçãoRESUMO
Type 2 diabetes (T2D) is on a notable rise worldwide, which leads to unfavorable outcomes during implant treatments. Surface modification of implants and exosome treatment have been utilized to enhance osseointegration. However, there has been insufficient approach to improve adverse osseointegration in T2D conditions. In this study, we successfully loaded TNF-α-treated mesenchymal stem cell (MSC)-derived exosomes onto micro/nano-network titanium (Ti) surfaces. TNF-α-licensed exosome-integrated titanium (TNF-exo-Ti) effectively enhanced M2 macrophage polarization in hyperglycemic conditions, with increased secretion of anti-inflammatory cytokines and decreased secretion of pro-inflammatory cytokines. In addition, TNF-exo-Ti pretreated macrophage further enhanced angiogenesis and osteogenesis of endothelial cells and bone marrow MSCs. More importantly, TNF-exo-Ti markedly promoted osseointegration in T2D mice. Mechanistically, TNF-exo-Ti activated macrophage autophagy to promote M2 polarization through inhibition of the PI3K/AKT/mTOR pathway, which could be abolished by PI3K agonist. Thus, this study established TNF-α-licensed exosome-immobilized titanium surfaces that could rectify macrophage immune states and accelerate osseointegration in T2D conditions.
Assuntos
Autofagia , Diabetes Mellitus Tipo 2 , Exossomos , Macrófagos , Camundongos Endogâmicos C57BL , Osseointegração , Titânio , Fator de Necrose Tumoral alfa , Titânio/química , Titânio/farmacologia , Animais , Exossomos/metabolismo , Autofagia/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Osseointegração/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Camundongos , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Polaridade Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismoRESUMO
PURPOSE: Implant-based breast reconstruction (IBR) is being increasingly performed with implant placed above the pectoral muscle (pre-pectoral), instead of below the pectoral muscle (sub-pectoral). Currently, there is a lack of comparative data on clinical and patient-perceived outcomes between pre- vs. sub-pectoral IBR. We investigated whether this difference in surgical approach influenced clinical or patient-perceived outcomes. METHODS: This prospective non-randomised longitudinal cohort study (ClinicalTrials.gov identifier: NCT04842240) recruited patients undergoing immediate IBR at the Leeds Breast Unit (Sep 2019-Sep 2021). Data collection included patient characteristics and post-operative complications. Patient-Reported Outcome Measures were collected using the BREAST-Q questionnaire at baseline, 2 weeks, 3- and 12-months post-surgery. RESULTS: Seventy-eight patients underwent IBR (46 patients pre-pectoral; 59% vs. 32 patients sub-pectoral; 41%). Similar complication rates were observed (15.2% pre-pectoral vs. 9.4% sub-pectoral; p = 0.44). Overall implant loss rate was 3.8% (6.5% pre-pectoral vs. 0% sub-pectoral; p = 0.13). Respective median Breast-Q scores for pre- and sub-pectoral IBR at 3 months were: breast satisfaction (58 vs. 48; p = 0.01), psychosocial well-being (60 vs. 57; p = 0.9), physical well-being (68 vs. 76; p = 0.53), and Animation Q scores (73 vs. 76; p = 0.45). Respective Breast-Q scores at 12 months were: breast satisfaction (58 vs. 53; p = 0.3), psychosocial well-being (59 vs. 60; p = 0.9), physical well-being (68 vs. 78; p = 0.18), and Animation Q scores (69 vs. 73; p = 0.4). CONCLUSIONS: This study demonstrates equivalent clinical and patient-perceived outcomes between pre- and sub-pectoral IBR. The study findings can be utilised to aid informed decision making regarding either surgical option.
RESUMO
PURPOSE: There has been a UK national directive to ensure that patients are offered reconstructive surgical options. We aimed to assess any change in oncoplastic practice over a 10-year period. METHODS: The surgical management of 7019 breast cancers was retrospectively assessed at Nightingale Breast Centre, Manchester University UK, from 2010 to 2019. The procedures were categorised into breast conservative surgery (BCS) and mastectomy ± immediate reconstruction. The data were analysed using inclusion and exclusion criteria. RESULTS: The overall rates of BCS and mastectomy were 60.1% and 39.9% respectively. No statistically significant change in the overall rates of BCS or mastectomy was observed over the last decade (p = 0.08). The rate of simple wide local excision (WLE) decreased from 98.7% to 89.3% (p < 0.001), whilst the rate of therapeutic mammoplasty (TM) increased from 1.3% to 8% (p < 0.01). The rate of chest wall perforator flaps (CWPF) changed from zero to account for 2.7% of all BCS by 2019. The overall rate of immediate breast reconstruction (IBR) did not significantly change over the study period, but it consistently remained above the national average of 27%. The rate of implant-based IBR increased from 61.3% to 76.5% (p = 0.012), whilst the rate of Latissimus Dorsi (LD) reconstruction decreased from 26.7% to 5.1% (p < 0.05). Additionally, the rate of nipple-sparing mastectomy significantly increased from 5.2% to 24%. CONCLUSION: No significant changes in the overall rates of BCS was observed, the rates of advanced breast conservation techniques, nipple-sparing mastectomy, and implant-based IBR all have increased, whilst the use of LD reconstruction decreased.
Assuntos
Neoplasias da Mama , Mamoplastia , Mastectomia , Humanos , Feminino , Mamoplastia/tendências , Mamoplastia/métodos , Mamoplastia/estatística & dados numéricos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/epidemiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Mastectomia/métodos , Mastectomia/estatística & dados numéricos , Mastectomia/tendências , Adulto , Idoso , Mastectomia Segmentar/métodos , Mastectomia Segmentar/estatística & dados numéricos , Reino Unido/epidemiologiaRESUMO
Foreign body reaction (FBR) is a prevalent yet often overlooked pathological phenomenon, particularly within the field of biomedical implantation. The presence of FBR poses a heavy burden on both the medical and socioeconomic systems. This review seeks to elucidate the protein "fingerprint" of implant materials, which is generated by the physiochemical properties of the implant materials themselves. In this review, the activity of macrophages, the formation of foreign body giant cells (FBGCs), and the development of fibrosis capsules in the context of FBR are introduced. Additionally, the relationship between various implant materials and FBR is elucidated in detail, as is an overview of the existing approaches and technologies employed to alleviate FBR. Finally, the significance of implant components (metallic materials and non-metallic materials), surface CHEMISTRY (charge and wettability), and physical characteristics (topography, roughness, and stiffness) in establishing the protein "fingerprint" of implant materials is also well documented. In conclusion, this review aims to emphasize the importance of FBR on implant materials and provides the current perspectives and approaches in developing implant materials with anti-FBR properties.
Assuntos
Reação a Corpo Estranho , Próteses e Implantes , Reação a Corpo Estranho/etiologia , Humanos , Próteses e Implantes/efeitos adversos , Animais , Materiais Biocompatíveis/química , Propriedades de Superfície , Células Gigantes de Corpo Estranho/patologiaRESUMO
Bioinspired nanotopography is a promising approach to generate antimicrobial surfaces to combat implant-associated infection. Despite efforts to develop bactericidal 1D structures, the antibacterial capacity of 2D structures and their mechanism of action remains uncertain. Here, hydrothermal synthesis is utilized to generate two 2D nanoflake surfaces on titanium (Ti) substrates and investigate the physiological effects of nanoflakes on bacteria. The nanoflakes impair the attachment and growth of Escherichia coli and trigger the accumulation of intracellular reactive oxygen species (ROS), potentially contributing to the killing of adherent bacteria. E. coli surface appendages type-1 fimbriae and flagella are not implicated in the nanoflake-mediated modulation of bacterial attachment but do influence the bactericidal effects of nanoflakes. An E. coli ΔfimA mutant lacking type-1 fimbriae is more susceptible to the bactericidal effects of nanoflakes than the parent strain, while E. coli cells lacking flagella (ΔfliC) are more resistant. The results suggest that type-1 fimbriae confer a cushioning effect that protects bacteria upon initial contact with the nanoflake surface, while flagella-mediated motility can lead to elevated membrane abrasion. This finding offers a better understanding of the antibacterial properties of nanoflake structures that can be applied to the design of antimicrobial surfaces for future medical applications.
Assuntos
Escherichia coli , Propriedades de Superfície , Titânio , Titânio/química , Titânio/farmacologia , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Espécies Reativas de Oxigênio/metabolismo , Nanoestruturas/química , Aderência Bacteriana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Fímbrias Bacterianas/efeitos dos fármacos , Fímbrias Bacterianas/metabolismoRESUMO
BACKGROUND: One of the main factors for the osseointegration of dental implants is the development of an adequate soft tissue barrier, mainly composed by collagen, which protects the implant from bacterial development. The structural features of the peri-implant collagen are influenced by the implant components and, in particular, by the type of the surface. In the clinical practice, healing abutments are characterized by smooth surfaces, named machined. Recently, a new laser technique, Synthegra, has been developed to obtain a topography-controlled surface with micrometric regular pores that seems reducing the risk of peri-implantitis. Based on this background, this study aims investigating the structural organization and spatial distribution of collagen surrounding healing abutments characterized by laser-treated and machined surfaces. METHODS: Gingiva portions surrounding custom-made healing abutments (HA), characterized by alternated laser-treated and machined surfaces, were collected and analyzed by combining Fourier Transform InfraRed Imaging (FTIRI) spectroscopy, a non-invasive and high-resolution bidimensional analytical technique, with histological and multivariate analyses. RESULTS: Masson's trichrome staining, specific for collagen, highlighted a massive presence of collagen in all the analyzed samples, evidencing a surface-related spatial distribution. The nature of collagen, investigated by the FTIRI spectroscopy, appeared more abundant close to the laser-treated surface, with a perpendicular disposition of the bundles respect to the HA; conversely, a parallel distribution was observed around the machined surface. A different secondary structure was also found, with a higher amount of triple helices and a lower quantity of random coils in collagen close to the laser treated surfaces. CONCLUSIONS: FTIRI spectroscopy demonstrates that the use of a laser treated transmucosal surface can improve the morphological organization of the peri-implant collagen, which presents a distribution more similar to that of natural teeth. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov Identifier: (Registration Number: NCT05754970). Registered 06/03/2023, retrospectively registered, https://clinicaltrials.gov/show/NCT05754970 .
Assuntos
Implantes Dentários , Colágeno , Gengiva/patologia , Lasers , Osseointegração , Propriedades de Superfície , HumanosRESUMO
BACKGROUND: Breast cancer is the world's most prevalent cancer, and many breast cancer patients undergo mastectomy as the choice of treatment, often with post-mastectomy breast reconstruction. Acellular dermal matrix (ADM) use has become a method to improve outcomes of reconstruction for these patients. We aimed to compare postoperative complications and patient-reported outcomes, which are still poorly characterized, between groups utilizing acellular dermal matrix during reconstruction and those without. MATERIALS AND METHODS: We searched electronic databases from inception to 16 June 2022 for randomized controlled trials and prospective cohort studies comparing the outcomes of patients who have and have not received acellular dermal matrix in implant-based breast reconstruction. The results were quantitatively combined and analyzed using random-effects models. RESULTS: A total of nine studies were included, representing 3161 breasts. There was no significant difference in postoperative outcomes, such as seroma formation (p = 0.51), hematomas (p = 0.20), infections (p = 0.21), wound dehiscence (p = 0.09), reoperations (p = 0.70), implant loss (p = 0.27), or skin necrosis (p = 0.21). Only two of the studies included evaluated patient-reported outcomes between the use and non-use of ADM in implant-based breast reconstruction using BREAST-Q questionnaire, as well as self-reported pain. There was no reported significant difference in BREAST-Q or pain scores. CONCLUSIONS: This meta-analysis shows comparable short- and long-term outcomes between ADM and non-ADM breast reconstruction, suggesting that the use of ADM may not be necessary in all cases given their additional cost. However, there is a paucity of data for patient-reported outcomes, and further research is required to determine whether ADM use affects patient-reported outcomes.
Assuntos
Derme Acelular , Implante Mamário , Implantes de Mama , Neoplasias da Mama , Mamoplastia , Humanos , Feminino , Mastectomia/métodos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/complicações , Estudos Prospectivos , Implantes de Mama/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Mamoplastia/métodos , Complicações Pós-Operatórias/etiologia , Dor/etiologia , Implante Mamário/efeitos adversos , Implante Mamário/métodos , Estudos RetrospectivosRESUMO
BACKGROUND: Minimal access breast surgery improves cosmetic outcomes over conventional breast surgery but still faces barriers in becoming standard procedure for breast reconstruction. This report introduces a novel technique of transaxillary reverse-sequence endoscopic nipple-sparing mastectomy (R-E-NSM) followed by direct-to-implant prepectoral breast reconstruction (DTI-PBR) and describes its clinical outcomes. METHODS: This prospective study enrolled patients who underwent R-E-NSM and DTI-PBR from March 2021 to December 2021 at a single institution. Perioperative data, surgical complications, oncologic outcomes, and patient- and surgeon-reported cosmetic results were noted. RESULTS: The 60 patients in this study who underwent 68 R-E-NSM and DTI-PBR had a mean age was 40.4 ± 10.3 years. The average durations of uni- and bilateral operations were 156.5 ± 48.3 min and 191.3 ± 36.1 min, respectively. The overall surgical complication rate was 13.3%, including 10.0% of patients with minor complications and 3.3% of patients with major complications. The study had one case (1.7%) of implant loss and one case (1.7%) of skin flap necrosis treated by reoperation. During the median follow-up period of 24 months, one patient (1.7%) who discontinued chemotherapy for myelosuppression experienced liver metastases 5 months postoperatively, and one patient experienced new-onset contralateral ductal carcinoma in situ 24 months postoperatively. The preoperative and 18-month postoperative Breast-Q scores for satisfaction with breasts, psychosocial well-being, sexual well-being, and chest well-being did not differ significantly, and the Scar-Q was 81.2 ± 14.5 points. The good-to-excellent rate in surgeon-reported cosmetic results reached 90%. CONCLUSIONS: Transaxillary R-E-NSM followed by DTI-PBR is a safe and efficient technique with high cosmetic outcomes and reliable medium-term oncologic results.
Assuntos
Implantes de Mama , Neoplasias da Mama , Mamoplastia , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Mastectomia/métodos , Estudos Prospectivos , Mamilos/cirurgia , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the safety and intraocular pressure (IOP)-lowering efficacy of 2 models of the travoprost intraocular implant (fast-eluting [FE] and slow-eluting [SE] types) from 1 of 2 phase 3 trials (the GC-010 trial). DESIGN: Multicenter, randomized, double-masked, sham-controlled, noninferiority trial. PARTICIPANTS: Patients with open-angle glaucoma or ocular hypertension having an unmedicated baseline mean diurnal IOP (average of 8 am, 10 am, and 4 pm time points) of ≥ 21 mmHg, and IOP of ≤ 36 mmHg at each of the 8 am, 10 am, and 4 pm timepoints at baseline. METHODS: Study eyes were randomized to the travoprost intraocular implant (FE implant [n = 200] or SE implant [n = 197] model) or to timolol ophthalmic solution 0.5% twice daily (n = 193). MAIN OUTCOME MEASURES: The primary outcome was mean change from baseline IOP in the study eye at 8 am and 10 am, at each of day 10, week 6, and month 3. Safety outcomes included adverse events (AEs) and ophthalmic assessments. RESULTS: Mean IOP reduction from baseline over the 6 time points ranged from 6.6 to 8.4 mmHg for the FE implant group, from 6.6 to 8.5 mmHg for the SE implant group, and from 6.5 to 7.7 mmHg for the timolol group. The primary efficacy end point was met; the upper limit of the 95% confidence interval of the difference between the implant groups and the timolol group was < 1 mmHg at all 6 time points. Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2%, and 10.8% of patients in the FE implant, SE implant, and timolol groups, respectively. The most common AEs included iritis (FE implant, 0.5%; SE implant, 5.1%), ocular hyperemia (FE implant, 3.0%; SE implant, 2.6%), reduced visual acuity (FE implant, 1.0%; SE implant, 4.1%; timolol, 0.5%), and IOP increased (FE implant, 3.5%; SE implant, 2.6%; timolol, 2.1%). One serious study eye AE occurred (endophthalmitis). CONCLUSIONS: The travoprost intraocular implant demonstrated robust IOP reduction over the 3-month primary efficacy evaluation period after a single administration. The IOP-lowering efficacy in both implant groups was statistically and clinically noninferior to that in the timolol group, with a favorable safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Assuntos
Anti-Hipertensivos , Implantes de Medicamento , Glaucoma de Ângulo Aberto , Pressão Intraocular , Hipertensão Ocular , Tonometria Ocular , Travoprost , Humanos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/fisiopatologia , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Travoprost/uso terapêutico , Travoprost/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Feminino , Masculino , Método Duplo-Cego , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Acuidade Visual/fisiologia , Timolol/administração & dosagem , Timolol/uso terapêutico , Timolol/efeitos adversos , Soluções Oftálmicas , Idoso de 80 Anos ou mais , AdultoRESUMO
PURPOSE: To report long-term results from a phase 1/2a clinical trial assessment of a scaffold-based human embryonic stem cell-derived retinal pigmented epithelium (RPE) implant in patients with advanced geographic atrophy (GA). DESIGN: A single-arm, open-label phase 1/2a clinical trial approved by the United States Food and Drug Administration. PARTICIPANTS: Patients were 69-85 years of age at the time of enrollment and were legally blind in the treated eye (best-corrected visual acuity [BCVA], ≤ 20/200) as a result of GA involving the fovea. METHODS: The clinical trial enrolled 16 patients, 15 of whom underwent implantation successfully. The implant was administered to the worse-seeing eye with the use of a custom subretinal insertion device. The companion nonimplanted eye served as the control. The primary endpoint was at 1 year; thereafter, patients were followed up at least yearly. MAIN OUTCOME MEASURES: Safety was the primary endpoint of the study. The occurrence and frequency of adverse events (AEs) were determined by scheduled eye examinations, including measurement of BCVA and intraocular pressure and multimodal imaging. Serum antibody titers were collected to monitor systemic humoral immune responses to the implanted cells. RESULTS: At a median follow-up of 3 years, fundus photography revealed no migration of the implant. No unanticipated, severe, implant-related AEs occurred, and the most common anticipated severe AE (severe retinal hemorrhage) was eliminated in the second cohort (9 patients) through improved intraoperative hemostasis. Nonsevere, transient retinal hemorrhages were noted either during or after surgery in all patients as anticipated for a subretinal surgical procedure. Throughout the median 3-year follow-up, results show that implanted eyes were more likely to improve by > 5 letters of BCVA and were less likely to worsen by > 5 letters compared with nonimplanted eyes. CONCLUSIONS: This report details the long-term follow-up of patients with GA to receive a scaffold-based stem cell-derived bioengineered RPE implant. Results show that the implant, at a median 3-year follow-up, is safe and well tolerated in patients with advanced dry age-related macular degeneration. The safety profile, along with the early indication of efficacy, warrants further clinical evaluation of this novel approach for the treatment of GA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.