RESUMO
BACKGROUND: Mixed reality (MR), a form of virtual reality (VR), provides an immersive and interactive experience for the user. Given VR's benefits in patients undergoing needle insertion procedures, MR's usability, impact on anxiety, and safety were evaluated in the blood donation setting. STUDY DESIGN AND METHODS: Whole blood donors ≥18 years old (yo) were enrolled at two blood centers and provided a MR headset with independently developed software to wear during blood donation. Pre- and post-donation questionnaires were conducted, and reaction data were reviewed. A post-study questionnaire was also completed by staff who assisted donors with MR. Descriptive statistics, bivariate analyses, and multinomial logistic regression were performed, and p values determined statistical significance between variables. RESULTS: A total of 282 donors completed the study. 84% wanted to try MR because it seemed fun/different/cool/interesting, and most staff (69%) and donors (68%) found MR easy to use. Baseline subjective anxiety, reported by 50.3% (more often in females, first-time donors, and donors <20 yo), was reduced by MR in 68.4% of donors, and there was a 3.6 times higher odds of anxiety reduction with MR. 54% of donors with baseline anxiety would use MR again with the highest future interest in young donors. Donor reactions while using MR were mild and included pre-faint reactions and hematomas. CONCLUSION: This study demonstrates the potential of MR in reducing donor anxiety, its feasibility during blood donation, and its safety in blood donors. MR is an innovative technology that holds promise to increase donor engagement, satisfaction, and retention.
Assuntos
Realidade Aumentada , Feminino , Humanos , Adolescente , Doadores de Sangue , Ansiedade/etiologia , Síncope , AgulhasRESUMO
PURPOSE: Significant time and resources are devoted to conducting orthopaedic biomechanics research; however, it is not known how these studies relate to their subsequent clinical studies. The purpose of the present study was to determine whether biomechanically superior treatments were associated with improved clinical outcomes as determined by analogous randomized controlled trials (RCTs). METHODS: A systematic review was conducted to find RCTs that tested a research question based on a prior biomechanical study. PubMed and SCOPUS databases were queried for orthopaedic randomized controlled trials, and full text articles were reviewed to find RCTs which cited biomechanical studies with analogous comparison groups. A random-effects multi-level logistic regression model was conducted examining the association between RCT outcome and biomechanics outcome, adjusting for multiple outcomes nested within study. RESULTS: In total, 20,261 articles were reviewed yielding 21 RCTs citing a total of 43 analogous biomechanical studies. In 7 instances (16.2%), the RCT and a cited biomechanical study showed concordant results (i.e. the superior treatment in the RCT was also the superior construct in the biomechanical study). RCT outcome was not associated with biomechanical outcome (ß = -1.50, standard error = 0.78, p = .05). CONCLUSION: This study assessed 21 orthopaedic RCTs with 43 corresponding biomechanical studies and found no association between superior biomechanical properties of a given orthopaedic treatment and improved clinical outcomes. Favourable biomechanical properties alone should not be the primary reason for selecting one treatment over another. Furthermore, RCTs based on biomechanical studies should be carefully designed to maximize the chance of providing clinically relevant insights.
Assuntos
Ortopedia , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Pertussis is a respiratory disease caused by the Gram-negative pathogen, Bordetella pertussis. The transition from a whole-cell pertussis vaccine (wP and DTP) to an acellular pertussis vaccine (aP, DTaP, and Tdap) correlates with an increase in pertussis cases, despite widespread vaccine implementation and coverage, and it is now appreciated that the protection provided by aP rapidly wanes. To recapitulate the localized immunity observed from natural infection, mucosal vaccination with aP was explored using the coughing rat model of pertussis. Overall, our goal was to evaluate the route of vaccination in the coughing rat model of pertussis. Immunity induced by both oral gavage and intranasal vaccination of aP in B. pertussis challenged rats over a 9-day infection was compared to intramuscular wP (IM-wP)- and IM-aP-immunized rats that were used as positive controls. Our data demonstrate that mucosal immunization of aP resulted in the production of anti-B. pertussis IgG antibody titers similar to IM-wP- and IM-aP-vaccinated controls postchallenge. IN-aP also induced anti-B. pertussis IgA antibodies in the nasal cavity. Immunization with IM-wP, IM-aP, IN-aP, and OG-aP immunization protected against B. pertussis-induced cough, whereas OG-aP immunization did not protect against respiratory distress. Mucosal immunization by both intranasal and oral gavage administration protected against acute inflammation and decreased bacterial burden in the lung compared to mock-vaccinated challenge rats. The data presented in this study suggest that mucosal vaccination with aP can induce a mucosal immune response and provide protection against B. pertussis challenge. This study highlights the potential benefits and uses of the coughing rat model of pertussis; however, further questions regarding waning immunity still require additional investigation.
Assuntos
Bordetella pertussis/imunologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Imunidade nas Mucosas , Coqueluche/prevenção & controle , Animais , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno/imunologia , Imunização , Ratos , Ratos Sprague-Dawley , Coqueluche/imunologiaRESUMO
Bordetella pertussis is a highly contagious bacterium that is the causative agent of whooping cough (pertussis). Currently, acellular pertussis vaccines (aP, DTaP, and Tdap) are used to prevent pertussis disease. However, it is clear that the aP vaccine efficacy quickly wanes, resulting in the reemergence of pertussis. Furthermore, recent work performed by the CDC suggest that current circulating strains are genetically distinct from strains of the past. The emergence of genetically diverging strains, combined with waning aP vaccine efficacy, calls for reevaluation of current animal models of pertussis. In this study, we used the rat model of pertussis to compare two genetically divergent strains Tohama 1 and D420. We intranasally challenged 7-week-old Sprague-Dawley rats with 108 viable Tohama 1 and D420 and measured the hallmark signs/symptoms of B. pertussis infection such as neutrophilia, pulmonary inflammation, and paroxysmal cough using whole-body plethysmography. Onset of cough occurred between 2 and 4 days after B. pertussis challenge, averaging five coughs per 15 min, with peak coughing occurring at day 8 postinfection, averaging upward of 13 coughs per 15 min. However, we observed an increase of coughs in rats infected with clinical isolate D420 through 12 days postchallenge. The rats exhibited increased bronchial restriction following B. pertussis infection. Histology of the lung and flow cytometry confirm both cellular infiltration and pulmonary inflammation. D420 infection induced higher production of anti-B. pertussis IgM antibodies compared to Tohama 1 infection. The coughing rat model provides a way of characterizing disease manifestation differences between B. pertussis strains.
Assuntos
Bordetella pertussis/fisiologia , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno , Coqueluche/etiologia , Animais , Biomarcadores , Bordetella pertussis/patogenicidade , Modelos Animais de Doenças , Ratos , Coqueluche/metabolismo , Coqueluche/patologiaRESUMO
Cirrhosis and hepatic encephalopathy (HE) is associated with an altered gut-liver-brain axis. Fecal microbial transplant (FMT) after antibiotics improves outcomes in HE, but the impact on brain function is unclear. The aim of this study is to determine the effect of colonization using human donors in germ-free (GF) mice on the gut-liver-brain axis. GF and conventional mice were made cirrhotic using carbon tetrachloride and compared with controls in GF and conventional state. Additional GF mice were colonized with stool from controls (Ctrl-Hum) and patients with cirrhosis (Cirr-Hum). Stools from patients with HE cirrhosis after antibiotics were pooled (pre-FMT). Stools from the same patients 15 days after FMT from a healthy donor were also pooled (post-FMT). Sterile supernatants were created from pre-FMT and post-FMT samples. GF mice were colonized using stools/sterile supernatants. For all mice, frontal cortex, liver, and small/large intestines were collected. Cortical inflammation, synaptic plasticity and gamma-aminobutyric acid (GABA) signaling, and liver inflammation and intestinal 16s ribosomal RNA microbiota sequencing were performed. Conventional cirrhotic mice had higher degrees of neuroinflammation, microglial/glial activation, GABA signaling, and intestinal dysbiosis compared with other groups. Cirr-Hum mice had greater neuroinflammation, microglial/glial activation, and GABA signaling and lower synaptic plasticity compared with Ctrl-Hum mice. This was associated with greater dysbiosis but no change in liver histology. Pre-FMT material colonization was associated with neuroinflammation and microglial activation and dysbiosis, which was reduced significantly with post-FMT samples. Sterile pre-FMT and post-FMT supernatants did not affect brain parameters. Liver inflammation was unaffected. Conclusion: Fecal microbial colonization from patients with cirrhosis results in higher degrees of neuroinflammation and activation of GABAergic and neuronal activation in mice regardless of cirrhosis compared with those from healthy humans. Reduction in neuroinflammation by using samples from post-FMT patients to colonize GF mice shows a direct effect of fecal microbiota independent of active liver inflammation or injury.
Assuntos
Córtex Cerebral , Disbiose/complicações , Encefalite/microbiologia , Encefalite/terapia , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Cirrose Hepática/microbiologia , Cirrose Hepática/terapia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Nucleic acid persists after symptom resolution and infectivity for many viral infections via delayed clearance of nucleic acid fragments, non-infectious particles, or transmissible virus. For Coronavirus Disease 2019 (COVID-19), the relationship between nasopharyngeal (NP) swab positivity, the development of antibodies against COVID-19, and clinical history are unclear. STUDY DESIGN AND METHODS: Individuals who recovered from COVID-19 and volunteered to donate convalescent plasma (CP) were screened by NP swab PCR, responded to a questionnaire, and were tested for anti-COVID-19 antibodies. RESULTS: A proportion of 11.8% of individuals tested positive for SARS-CoV-2 by NP swab PCR greater than 14 days after the resolution of symptoms of active disease, including one donor who had asymptomatic disease and tested positive by NP swab 41 days after her initial diagnosis. Clinical history did not show a significant correlation with persistence of NP swab positivity. Also, NP swab positivity >14 days from symptom resolution did not correlate with anti-COVID-19 serology results. IgG anti-SARS-CoV-2 spike antibody strength correlated with hospitalization for COVID-19 using two different assays. Total anti-SARS-CoV-2 nucleocapsid antibody strength correlated with time from symptom resolution to sample collection and symptom duration. CONCLUSIONS: SARS-CoV-2 nucleic acid is detectable long after the resolution of symptoms in a significant percentage of previously diagnosed individuals, which is important to consider when interpreting PCR swab results. Persistence of PCR positivity does not correlate with antibody strength or symptoms of COVID-19. If anti-spike antibody is used to assess CP potency, individuals who suffered severe COVID-19 disease symptoms may represent better donors.
Assuntos
Doadores de Sangue , Teste de Ácido Nucleico para COVID-19 , COVID-19/terapia , COVID-19/virologia , Seleção do Doador , Nasofaringe/virologia , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/isolamento & purificação , Adulto , Idoso , Anticorpos Antivirais/sangue , COVID-19/sangue , Teste Sorológico para COVID-19 , Convalescença , Feminino , Humanos , Imunização Passiva , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Avaliação de Sintomas , Adulto Jovem , Soroterapia para COVID-19RESUMO
BACKGROUND: When the coronavirus pandemic caused widespread school and business closures in March 2020, blood drives were canceled and the supply of blood decreased suddenly in the United States (US). In response, hospital-based transfusion medicine physicians instituted policies to conserve blood and decrease blood product usage. These efforts were aided by the US Surgeon General recommendation to cancel all elective procedures. Nevertheless, the duration, severity, and impact of the pandemic on the national blood supply was uncertain. Hospitals with in-house donor programs had the opportunity not only to control demand, but also increase supply. STUDY DESIGN AND METHODS: A hospital-based blood donor center was rapidly mobilized to increase the supply of in-house collected blood, in order to counteract a sudden but potentially long-term depletion of the national blood supply during a pandemic. RESULTS: Collections increased approximately five-fold above baseline for whole blood units, while apheresis platelet units were maintained at the historical average for the blood donor center. Cancellation of elective procedures showed a modest, but not yet statistically significant decrease in average blood product usage per day, nevertheless the in-house collection rate was sufficient to meet demand. CONCLUSION: A hospital-based blood donor center can quickly increase collection volumes and capacity in the face of a national emergency or pandemic. The desire to collect units should be balanced with safety concerns, need for sustainability, and blood product demand.
Assuntos
Betacoronavirus , Bancos de Sangue , Doadores de Sangue , Transfusão de Sangue , Infecções por Coronavirus/epidemiologia , Seleção do Doador , Pandemias , Pneumonia Viral/epidemiologia , COVID-19 , Feminino , Humanos , Masculino , SARS-CoV-2RESUMO
OBJECTIVES: Bone and joint infections caused by Staphylococcus aureus are becoming increasingly difficult to treat due to rising antibiotic resistance, resilient biofilms and intracellular survival of S. aureus. It has been challenging to identify and develop antimicrobial agents that can be used to kill extracellular and intracellular bacteria while having limited toxicity towards host cells. In addressing this challenge, this study investigates the antimicrobial efficacy and toxicity of silver nanoparticles (AgNPs). METHODS: Intracellular bacteria were generated using a co-culture model of human osteoblast cells and S. aureus. Extracellular and intracellular S. aureus were treated with AgNPs, antibiotics and their combinations, and numbers of colonies were quantified. Toxicity of AgNPs against human osteoblast cells was determined by quantifying the number of viable cells after treatment. RESULTS: AgNPs demonstrated excellent antimicrobial activity against extracellular S. aureus with a 100% killing efficacy at concentrations as low as 56 µM, along with a high intracellular killing efficacy of 76% at 371 µM. AgNPs were non-toxic or slightly toxic towards human osteoblasts at the concentrations studied (up to 927 µM). Moreover, smaller-sized (40 nm) AgNPs were more efficacious in killing bacteria compared with their larger-sized (100 nm) counterparts and synergistic antimicrobial effects against extracellular bacteria were observed when AgNPs were combined with gentamicin. CONCLUSIONS: AgNPs and their combination with antibiotics have demonstrated high extracellular and intracellular bacterial killing and presented unique aspects for potential clinical applications, especially for chronic and recurrent infections where intracellular bacteria may be the cause.
Assuntos
Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Osteoblastos , Compostos de Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/química , Linhagem Celular Tumoral , Técnicas de Cocultura , Humanos , Compostos de Prata/químicaRESUMO
PURPOSE: This study examined a palmar beak fracture model to determine which thumb carpometacarpal (CMC) joint ligament is the primary ligament relevant to the pattern of injury. METHODS: Six fresh-frozen cadaveric wrists were used. The radius, ulna, and first metacarpal were secured and tested with a materials testing system, holding the wrist in 20° extension, 20° ulnar deviation, and 30° palmar abduction of the first metacarpal. Testing consisted of preconditioning cycles followed by compressive loading at 100 mm/s. We confirmed fractures with fluoroscopy and dissected the specimens to examine the CMC joint ligaments. The metacarpal was stressed through a range of motion to determine which maneuvers reduced or displaced the fractures. RESULTS: Our model successfully created palmar beak fractures in all cadaveric specimens. All fractures were displaced and intra-articular. The anterior oblique ligament (AOL) was thin and partially attached to the palmar beak fracture fragment. The ulnar collateral ligament was attached in its entirety to the fracture fragment and represented a thicker, more robust ligament compared with the AOL. Radial abduction and pronation of the metacarpal reduced fracture displacement. Extension of the CMC joint or tensioning the AOL did not decrease fracture displacement. CONCLUSIONS: This model successfully created a reproducible and clinically relevant palmar beak fracture in a biomechanical setting. The primary ligament attached to the palmar beak fracture fragment was the ulnar collateral ligament, and not the AOL as previously described. These findings suggest that the AOL may not be a substantial contributor to palmar beak fracture morphology. CLINICAL RELEVANCE: A refined description of the ligamentous anatomy of the palmar break fracture enhances opportunities for improved reduction and treatment of this common hand injury.
Assuntos
Fratura-Luxação , Fraturas Intra-Articulares , Ossos Metacarpais/lesões , Polegar/lesões , Cadáver , Fratura-Luxação/diagnóstico por imagem , Fratura-Luxação/patologia , Humanos , Fraturas Intra-Articulares/diagnóstico por imagem , Fraturas Intra-Articulares/patologia , Ligamentos Articulares/anatomia & histologia , Masculino , Ossos Metacarpais/diagnóstico por imagem , Ossos Metacarpais/patologia , Pessoa de Meia-Idade , Modelos Biológicos , Polegar/diagnóstico por imagem , Polegar/patologiaRESUMO
BACKGROUND: The early results of reverse shoulder arthroplasty (RSA) were influenced to some extent by the use of first-generation implants and surgeons' learning curves, resulting in relatively high reoperation rates. The purpose of this study was to quantify the burden of and identify the indications for reoperation after primary RSA using contemporary implants and techniques. METHODS: A retrospective review of 1649 primary RSAs implanted consecutively between 2009 and 2015 at a single institution was conducted. All arthroplasties were performed by 5 fellowship-trained shoulder surgeons at a tertiary referral center. Demographic characteristics, indications for primary RSA, and reoperations were analyzed and categorized for trends associated with each type of reoperation performed. RESULTS: A total of 39 reoperations (2.37%) were performed for a variety of indications. Overall, only a few patients with infection or instability required reoperation (0.55%). The most common indications for reoperation were related to the humeral component (1.03%); the majority of humeral component complications were related to a specific design flaw of 1 implant system. RSAs performed for proximal humeral fracture sequelae more commonly underwent reoperation owing to instability or humeral component-related issues; all 4 cases of aseptic humeral stem loosening occurred in the setting of proximal humeral fracture sequela treatment. Only 0.36% of all primary RSAs required reoperation because of glenoid complications. CONCLUSIONS: Primary RSA performed with contemporary implants and surgical techniques seems to be associated with a very low rate of reoperation. The most common reasons for reoperation were humeral component fracture for 1 particular implant, humeral loosening, dislocation, infection, and glenoid failure, each occurring at a rate under 1%.
Assuntos
Artroplastia do Ombro/instrumentação , Falha de Prótese/efeitos adversos , Reoperação/estatística & dados numéricos , Prótese de Ombro , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Ombro/métodos , Feminino , Humanos , Instabilidade Articular/cirurgia , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Infecções Relacionadas à Prótese/cirurgia , Estudos Retrospectivos , Fraturas do Ombro/cirurgia , Articulação do Ombro/cirurgia , Adulto JovemRESUMO
INTRODUCTION: The importance of imaging surveillance after treatment for lung cancer is not well characterized. We examined the association between initial guideline recommended imaging surveillance and survival among early-stage resected non-small-cell lung cancer (NSCLC) patients. METHODS: A retrospective study was conducted using Surveillance, Epidemiology, and End Results-Medicare data (1995-2010). Surgically resected patients, with stage I and II NSCLC, were categorized by imaging received during the initial surveillance period (4-8 mo) after surgery. Primary outcome was overall survival. Secondary treatment interventions were examined as intermediary outcomes. RESULTS: Most (88%) patients had at least one outpatient clinic visit, and 24% received an initial computerized tomography (CT) during the first surveillance period. Five-year survival by initial surveillance imaging was 61% for CT, 58% for chest radiography, and 60% for no imaging. After adjustment, initial CT was not associated with improved overall survival (hazard ratio [HR], 1.04; 95% confidence interval [CI] 0.96-1.14). On subgroup analysis, restricted to patients with demonstrated initial postoperative follow-up, CT was associated with a lower overall risk of death for stage I patients (HR, 0.85; 95% CI, 0.74-0.98), but not for stage II (HR, 1.01; 95% CI, 0.71-1.42). There was no significant difference in rates of secondary interventions predicted by type of initial imaging surveillance. CONCLUSIONS: Initial surveillance CT is not associated with improved overall or lung cancer-specific survival among early-stage NSCLC patients undergoing surgical resection. Stage I patients with early follow-up may represent a subpopulation that benefits from initial surveillance although this may be influenced by healthy patient selection bias.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Pneumonectomia , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Programa de SEER , Análise de SobrevidaRESUMO
BACKGROUND: Despite recent advances in the investigation of myeloproliferative neoplasms (MPN), the impact of genetic heterogeneity on its molecular pathogenesis has not been fully elucidated. Thus, in this study, we aim to characterize the genetic complexity in Korean patients with polycythemia vera (PV) and essential thrombocythemia (ET). METHODS: We conducted association studies using 84 single-nucleotide polymorphisms (SNPs) in 229 patients (96 with PV and 133 with ET) and 170 controls. Further, whole-genome sequencing was performed in six patients (two with JAK2 V617F and four with wild-type JAK2), and putative somatic mutations were validated in a further 69 ET patients. Clinical and laboratory characteristics were also analyzed. RESULTS: Several germline SNPs and the 46 haplotype were significantly associated with PV and ET. Three somatic mutations in MPDZ, IQCH, and CALR genes were selected and validated. The frequency of the CALR mutation was 58.0% (40/69) in ET patients, who did not carry JAK2/MPL mutations. Moreover, compared with JAK2 V617F-positive patients, those with CALR mutations showed lower hemoglobin and hematocrit levels (P = 0.004 and P = 0.002, respectively), higher platelet counts (P =0.008), and a lower frequency of cytoreductive therapy (P = 0.014). CONCLUSION: This study was the first comprehensive investigation of the genetic characteristics of Korean patients with PV and ET. We found that somatic mutations and the 46 haplotype contribute to PV and ET pathogenesis in Korean patients.
Assuntos
Predisposição Genética para Doença/genética , Janus Quinase 2/genética , Policitemia Vera/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Trombopoetina/genética , Trombocitemia Essencial/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte/genética , Análise Mutacional de DNA , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Policitemia Vera/epidemiologia , República da Coreia/epidemiologia , Estatísticas não Paramétricas , Trombocitemia Essencial/epidemiologia , Adulto JovemRESUMO
To address a donor kidney shortage, marginal grafts have been applied in deceased donor kidney transplantation (DDKT). These grafts exhibit comparatively unfavorable outcomes, particularly when cold ischemia time (CIT) is prolonged. Hypothermic machine perfusion (HMP) has been investigated to mitigate the effects of prolonged CIT during graft transport. The present case involved successful management of the longest CIT recorded in Korea by employing HMP in DDKT. The donor was a 54-year-old man (Korean Kidney Donor Profile Index, 82%) with diabetes. The recipient, a 51-year-old man on peritoneal dialysis, had end-stage renal disease secondary to diabetic nephropathy. Following procurement, the left kidney was preserved using HMP. Inclement weather delayed graft transportation; consequently, the total CIT was 28 hours and 6 minutes, with the kidney preserved by HMP for 22 hours and 35 minutes. Postoperative graft function gradually recovered, and urine output was satisfactory. Delayed graft function was not observed, and the patient was discharged on postoperative day 13 without significant complications. Five months after surgery, his serum creatinine level was 1.7 mg/dL. Successful DDKT with a marginal donor graft via HMP, despite the longest CIT yet observed in Korea, underscores the usefulness of HMP in enhancing graft quality and preserving function.
RESUMO
Pulmonary delivery of antibiotics is an effective strategy in treating bacterial lung infection for cystic fibrosis patients, by achieving high local drug concentrations and reducing overall systemic exposure compared to systemic administration. However, the inherent anatomical lung defense mechanisms, formulation characteristics, and drug-device combination determine the treatment efficacy of the aerosol delivery approach. In this study, we prepared a new tobramycin (Tobi) dry powder aerosol using excipient enhanced growth (EEG) technology and evaluated the in vitro and in vivo aerosol performance. We further established a Pseudomonas aeruginosa-induced lung infection rat model using an in-house designed novel liquid aerosolizer device. Notably, novel liquid aerosolizer yields comparable lung infection profiles despite administering 3-times lower P. aeruginosa CFU per rat in comparison to the conventional intratracheal administration. Dry powder insufflator (e.g. Penn-Century DP-4) to administer small powder masses to experimental animals is no longer commercially available. To address this gap, we developed a novel rat air-jet dry powder insufflator (Rat AJ DPI) that can emit 68-70 % of the loaded mass for 2 mg and 5 mg of Tobi-EEG powder formulations, achieving a high rat lung deposition efficiency of 79 % and 86 %, respectively. Rat AJ DPI can achieve homogenous distribution of Tobi EEG powder formulations at both loaded mass (2 mg and 5 mg) over all five lung lobes in rats. We then demonstrated that Tobi EEG formulation delivered by Rat AJ DPI can significantly decrease CFU counts in both trachea and lung lobes at 2 mg (p < 0.05) and 5 mg (p < 0.001) loaded mass compared to the untreated P. aeruginosa-infected group. Tobi EEG powder formulation delivered by the novel Rat AJ DPI showed excellent efficiencies in substantially reducing the P. aeruginosa-induced lung infection in rats.
Assuntos
Antibacterianos , Inaladores de Pó Seco , Pós , Infecções por Pseudomonas , Pseudomonas aeruginosa , Ratos Sprague-Dawley , Tobramicina , Animais , Tobramicina/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Administração por Inalação , Antibacterianos/administração & dosagem , Ratos , Aerossóis , Pulmão/microbiologia , Masculino , Excipientes/químicaRESUMO
Effective hospital environmental cleaning requires proper technique and training. Highlight is a novel additive that colorizes bleach wipes to help visualize wiped surfaces and fades to colorless to confirm effective cleaning. In a 401-bed hospital study, Highlight reduced fluorescent marker removal failure rates from a baseline of 12.4% to 0.6%.
Assuntos
Anti-Infecciosos , Desinfetantes , Humanos , Desinfetantes/farmacologia , Desinfecção/métodos , Hospitais , Centros Médicos AcadêmicosRESUMO
Artificial intelligence (AI) applied to medicine offers immense promise, in addition to safety and regulatory concerns. Traditional AI produces a core algorithm result, typically without a measure of statistical confidence or an explanation of its biological-theoretical basis. Efforts are underway to develop explainable AI (XAI) algorithms that not only produce a result but also an explanation to support that result. Here we present a framework for classifying XAI algorithms applied to clinical medicine: An algorithm's clinical scope is defined by whether the core algorithm output leads to observations (eg, tests, imaging, clinical evaluation), interventions (eg, procedures, medications), diagnoses, and prognostication. Explanations are classified by whether they provide empiric statistical information, association with a historical population or populations, or association with an established disease mechanism or mechanisms. XAI implementations can be classified based on whether algorithm training and validation took into account the actions of health care providers in response to the insights and explanations provided or whether training was performed using only the core algorithm output as the end point. Finally, communication modalities used to convey an XAI explanation can be used to classify algorithms and may affect clinical outcomes. This framework can be used when designing, evaluating, and comparing XAI algorithms applied to medicine.
RESUMO
Pseudomonas aeruginosa is a common cause of hospital-acquired infections, including central line-associated bloodstream infections and ventilator-associated pneumonia. Unfortunately, effective control of these infections can be difficult, in part due to the prevalence of multi-drug resistant strains of P. aeruginosa. There remains a need for novel therapeutic interventions against P. aeruginosa, and the use of monoclonal antibodies (mAb) is a promising alternative strategy to current standard of care treatments such as antibiotics. To develop mAbs against P. aeruginosa, we utilized ammonium metavanadate, which induces cell envelope stress responses and upregulates polysaccharide expression. Mice were immunized with P. aeruginosa grown with ammonium metavanadate and we developed two IgG2b mAbs, WVDC-0357 and WVDC-0496, directed against the O-antigen lipopolysaccharide of P. aeruginosa. Functional assays revealed that WVDC-0357 and WVDC-0496 directly reduced the viability of P. aeruginosa and mediated bacterial agglutination. In a lethal sepsis model of infection, prophylactic treatment of mice with WVDC-0357 and WVDC-0496 at doses as low as 15 mg/kg conferred 100% survival against challenge. In both sepsis and acute pneumonia models of infection, treatment with WVDC-0357 and WVDC-0496 significantly reduced bacterial burden and inflammatory cytokine production post-challenge. Furthermore, histopathological examination of the lungs revealed that WVDC-0357 and WVDC-0496 reduced inflammatory cell infiltration. Overall, our results indicate that mAbs directed against lipopolysaccharide are a promising therapy for the treatment and prevention of P. aeruginosa infections.
Assuntos
Anticorpos Antibacterianos , Anticorpos Monoclonais , Lipopolissacarídeos , Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Feminino , Camundongos , Anticorpos Antibacterianos/imunologia , Anticorpos Monoclonais/imunologia , Aderência Bacteriana , Carga Bacteriana/imunologia , Convalescença , Mediadores da Inflamação/imunologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/imunologia , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/prevenção & controle , Pseudomonas aeruginosa/imunologia , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/prevenção & controle , Sepse/imunologia , Sepse/microbiologia , Sepse/prevenção & controleRESUMO
The rise of antimicrobial-resistant bacterial infections is a crucial health concern in the 21st century. In particular, antibiotic-resistant Pseudomonas aeruginosa causes difficult-to-treat infections associated with high morbidity and mortality. Unfortunately, the number of effective therapeutic interventions against antimicrobial-resistant P. aeruginosa infections continues to decline. Therefore, discovery and development of alternative treatments are necessary. Here, we present pre-clinical efficacy studies on an anti-P. aeruginosa therapeutic monoclonal antibody. Using hybridoma technology, we generated a monoclonal antibody and characterized its binding to P. aeruginosa in vitro using ELISA and fluorescence correlation spectroscopy. We also characterized its function in vitro and in vivo against P. aeruginosa. The anti-P. aeruginosa antibody (WVDC-5244) bound P. aeruginosa clinical strains of various serotypes in vitro, even in the presence of alginate exopolysaccharide. In addition, WVDC-5244 induced opsonophagocytic killing of P. aeruginosa in vitro in J774.1 murine macrophage, and complement-mediated killing. In a mouse model of acute pneumonia, prophylactic administration of WVDC-5244 resulted in an improvement of clinical disease manifestations and reduction of P. aeruginosa burden in the respiratory tract compared to the control groups. This study provides promising pre-clinical efficacy data on a new monoclonal antibody with therapeutic potential for P. aeruginosa infections.
Assuntos
Pneumonia , Infecções por Pseudomonas , Camundongos , Animais , Pseudomonas aeruginosa , Pneumonia/microbiologia , Anticorpos Monoclonais/uso terapêutico , Hibridomas/metabolismo , Proteínas do Sistema Complemento , Infecções por Pseudomonas/microbiologiaRESUMO
Fatty degeneration of chronically injured muscle is a commonly recognized consequence of massive rotator cuff tears. Current surgical treatments are unable to alter or reverse the progression of fatty degeneration and are associated with poor functional outcomes in these patients. Therefore, a better understanding of the pathophysiology of fatty degeneration is required. As such, recent discoveries in stem cell biology and new animal models have significantly advanced our understanding of the cellular and molecular basis of fatty degeneration. Future studies will facilitate development of novel treatments to prevent the progression of fatty degeneration and improve muscle regeneration in patients with massive rotator cuff tears.