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1.
Science ; 385(6713): eadi1650, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39236183

RESUMEN

Skin identity is controlled by intrinsic features of the epidermis and dermis and their interactions. Modifying skin identity has clinical potential, such as the conversion of residual limb and stump (nonvolar) skin of amputees to pressure-responsive palmoplantar (volar) skin to enhance prosthesis use and minimize skin breakdown. Greater keratin 9 (KRT9) expression, higher epidermal thickness, keratinocyte cytoplasmic size, collagen length, and elastin are markers of volar skin and likely contribute to volar skin resiliency. Given fibroblasts' capacity to modify keratinocyte differentiation, we hypothesized that volar fibroblasts influence these features. Bioprinted skin constructs confirmed the capacity of volar fibroblasts to induce volar keratinocyte features. A clinical trial of healthy volunteers demonstrated that injecting volar fibroblasts into nonvolar skin increased volar features that lasted up to 5 months, highlighting a potential cellular therapy.


Asunto(s)
Refuerzo Biomédico , Bioimpresión , Dermis , Epidermis , Fibroblastos , Queratinocitos , Adulto , Femenino , Humanos , Masculino , Amputados , Diferenciación Celular , Colágeno/metabolismo , Dermis/citología , Dermis/metabolismo , Elastina/metabolismo , Epidermis/metabolismo , Fibroblastos/citología , Fibroblastos/trasplante , Mano , Queratina-9/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Refuerzo Biomédico/métodos
2.
Vaccine ; 42(24): 126251, 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39226786

RESUMEN

This phase 1 trial assessed the safety and immunogenicity of an investigational tetanus/diphtheria/acellular pertussis vaccine combined with CpG 1018 adjuvant 1500 µg (Tdap-1018 1500 µg) or 3000 µg (Tdap-1018 3000 µg) in adults and adolescents. In this randomized, active-controlled, multicenter, dose-escalation trial, healthy participants aged 10 to 22 years received 1 dose of Tdap-1018 1500 µg, Tdap-1018 3000 µg, or Boostrix. Geometric mean concentrations (GMCs) and booster response rates (BRRs) for antibodies against pertussis (pertussis toxin, filamentous hemagglutinin, pertactin), tetanus, and diphtheria antigens, and neutralizing antibodies against pertussis toxin were assessed 4 weeks after vaccination. Safety and tolerability were assessed for solicited post-injection reactions within 7 days after vaccination and unsolicited adverse events up to 12 weeks after vaccination. Of 117 enrolled participants, 80 adults (92%) and 30 adolescents (100%) completed the study. Both Tdap-1018 formulations were generally well tolerated, with no vaccine-related serious adverse events. Frequency and severity in post-injection reactions after Tdap-1018 administration were similar to Boostrix except for higher proportions of moderate pain for Tdap-1018. In adults at week 4, ratio of GMCs and BRRs for all antigens in the 3000-µg group were similar to or higher than Boostrix, with significantly higher GMC ratios for anti-pertussis toxin (2.1 [1.5-3.0]) and anti-tetanus (1.8 [1.1-2.9]) and significantly higher BRRs for anti-pertussis toxin (difference [95% CI]: 34.5% [13.4-54.6]), anti-pertactin (19.2% [4.4-38.1]), and anti-tetanus (30.0% [3.6-52.7]) antibodies. For adolescents, in the 3000-µg group, ratio of GMCs and BRRs were similar to or higher than Boostrix for all antigens. Both Tdap-1018 formulations showed acceptable safety and tolerability profiles. Tdap-1018 3000 µg induced similar or higher immune responses than Boostrix. ACTRN12620001177943 (Australian New Zealand Clinical Trials Registry; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12620001177943p).


Asunto(s)
Adyuvantes Inmunológicos , Anticuerpos Antibacterianos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Inmunización Secundaria , Oligodesoxirribonucleótidos , Tos Ferina , Humanos , Adolescente , Femenino , Masculino , Anticuerpos Antibacterianos/sangre , Inmunización Secundaria/métodos , Adulto , Adulto Joven , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Niño , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/inmunología , Tos Ferina/prevención & control , Tos Ferina/inmunología , Anticuerpos Neutralizantes/sangre , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Tétanos/prevención & control , Tétanos/inmunología , Voluntarios Sanos , Inmunogenicidad Vacunal
3.
Plast Reconstr Surg Glob Open ; 12(8): e6101, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39188965

RESUMEN

The T-line hernia mesh is a synthetic, polypropylene mesh with mesh suture extensions designed to prevent anchor point failure by evenly distributing tension across the soft tissue. Previous studies have demonstrated the success of onlay ventral hernia repair with T-line hernia mesh, but retrorectus applications of the mesh have not yet been characterized. This technique article illustrates technical descriptions and clinical applications of the T-line hernia mesh in the retrorectus plane.

4.
JTCVS Tech ; 26: 86-88, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39161544
5.
J Cardiothorac Surg ; 19(1): 466, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054519

RESUMEN

BACKGROUND: Lung transplantation (LT) represents a high-risk procedure for end-stage lung diseases. This study describes the outcomes of patients undergoing LT that require massive transfusions as defined by the universal definition of perioperative bleeding (UDPB). METHODS: Adult patients who underwent bilateral LT at a single academic center were surveyed retrospectively. Patients were grouped by insignificant, mild, or moderate perioperative bleeding (insignificant-to-moderate bleeders) and severe or massive perioperative bleeding (severe-to-massive bleeders) based on the UDPB classification. Outcomes included 1-year survival and primary graft dysfunction (PGD) of grade 3 at 72 h postoperatively. Multivariable models were adjusted for recipient age, sex, body mass index (BMI), Lung allocation score (LAS), preoperative hemoglobin (Hb), preoperative extracorporeal membrane oxygenation (ECMO) status, transplant number, and donor status. An additional multivariable model was created to find preoperative and intraoperative predictors of severe-to-massive bleeding. A p-value less than 0.05 was selected for significance. RESULTS: A total of 528 patients were included, with 357 insignificant-to-moderate bleeders and 171 severe-to-massive bleeders. Postoperatively, severe-to-massive bleeders had higher rates of PGD grade 3 at 72 h, longer hospital stays, higher mortality rates at 30 days and one year, and were less likely to achieve textbook outcomes for LT. They also required postoperative ECMO, reintubation for over 48 h, tracheostomy, reintervention, and dialysis at higher rates. In the multivariate analysis, severe-to-massive bleeding was significantly associated with adverse outcomes after adjusting for recipient and donor factors, with an odds ratio of 7.73 (95% CI: 4.27-14.4, p < 0.001) for PGD3 at 72 h, 4.30 (95% CI: 2.30-8.12, p < 0.001) for 1-year mortality, and 1.75 (95% CI: 1.52-2.01, p < 0.001) for longer hospital stays. Additionally, severe-to-massive bleeders were less likely to achieve textbook outcomes, with an odds ratio of 0.07 (95% CI: 0.02-0.16, p < 0.001). Preoperative and intraoperative predictors of severe/massive bleeding were identified, with White patients having lower odds compared to Black patients (OR: 041, 95% CI: 0.22-0.80, p = 0.008). Each 1-unit increase in BMI decreased the odds of bleeding (OR: 0.89, 95% CI: 0.83-0.95, p < 0.001), while each 1-unit increase in MPAP increased the odds of bleeding (OR: 1.04, 95% CI: 1.02-1.06, p < 0.001). First-time transplant recipients had lower risk (OR: 0.16, 95% CI: 0.06-0.36, p < 0.001), whereas those with DCD donors had a higher risk of severe-to-massive bleeding (OR: 3.09, 95% CI: 1.63-5.87, p = 0.001). CONCLUSION: These results suggest that patients at high risk of massive bleeding require higher utilization of hospital resources. Understanding their outcomes is important, as it may inform future decisions to transplant comparable patients.


Asunto(s)
Trasplante de Pulmón , Humanos , Estudios Retrospectivos , Masculino , Femenino , Trasplante de Pulmón/efectos adversos , Persona de Mediana Edad , Adulto , Hemorragia Posoperatoria/epidemiología , Factores de Riesgo , Transfusión Sanguínea/estadística & datos numéricos , Resultado del Tratamiento
6.
Iran J Otorhinolaryngol ; 36(3): 475-482, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38745683

RESUMEN

Introduction: COVID-19 infection was accompanied by otologic symptoms, a pattern that was captured early by Google Trends. The objective of this study is to investigate searches for otologic symptoms and identify correlations with the pandemic onset. Materials and Methods: Search interest for otologic symptoms was gathered using Google Trends from two years before and two years following the pandemic start date. A two-tailed Mann-Whitney U test was used to identify significant changes and effect size. Results: In total, search interest for 14 terms was collected, with significant changes identified in 11. Six terms showed increased search interest, with the most significant rises observed for headache (r=0.589, p<0.001), dizziness (r=0.554, p<0.001), and tinnitus (r=0.410, p<0.001). Search interest decreased for five terms, with the most notable declines found in searches for migraine headache (r=0.35, p<0.001) and phonophobia (r=0.22, p=0.002). No significant changes were seen in ear pressure (p=0.142), neck pain (p=0.935), and sudden hearing loss (p=0.863) searches. Conclusion: COVID-19 infection is often accompanied otologic symptoms and holds a diagnostic role. Fluctuating search interest may be attributed to a true increase in cases, media trends, or people's desires to stay informed. Google Trends robustly captured trends in search interest and presented itself as a valuable epidemiological tool.

7.
ACS Appl Mater Interfaces ; 16(20): 26613-26623, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38728055

RESUMEN

Strain gauges, particularly for wearable sensing applications, require a high degree of stretchability, softness, sensitivity, selectivity, and linearity. They must also steer clear of challenges such as mechanical and electrical hysteresis, overshoot behavior, and slow response/recovery times. However, current strain gauges face challenges in satisfying all of these requirements at once due to the inevitable trade-offs between these properties. Here, we present an innovative method for creating strain gauges from spongy Ag foam through a steam-etching process. This method simplifies the traditional, more complex, and costly manufacturing techniques, presenting an eco-friendly alternative. Uniquely, the strain gauges crafted from this method achieve an unparalleled gauge factor greater than 8 × 103 at strains exceeding 100%, successfully meeting all required attributes without notable trade-offs. Our work includes systematic investigations that reveal the intricate structure-property-performance relationship of the spongy Ag foam with practical demonstrations in areas such as human motion monitoring and human-robot interaction. These breakthroughs pave the way for highly sensitive and selective strain gauges, showing immediate applicability across a wide range of wearable sensing applications.

8.
J Reconstr Microsurg ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38782026

RESUMEN

BACKGROUND: Reconstruction of upper extremity osseous diaphyseal defects often requires complex reconstructions. In this study, we characterized and summarized the available literature on free vascularized bone flap (VBF) reconstruction for upper extremity diaphyseal defects. METHODS: A scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews was conducted. A literature search of major electronic databases was conducted to identify journal articles relating to the management of VBF reconstruction of upper limb long bone defects. Articles with patient-level data were included. Descriptive statistics were performed using Python. RESULTS: Overall, 364 patients were included in this study. The most common indications for VBFs included atrophic nonunion (125, 34.3%), postoncologic resection (125, 34.3%), septic nonunion (56, 15.4%), and trauma (36, 9.9%). Mean defect size was 8.53 ± 5.14 cm. A total of 67 (18.4%) cases had defects < 6 cm, and 166 cases (45.6%) had defects > 6 cm. The fibula was the most utilized VBF (272, 74.73%), followed by the medial femoral condyle flap (69, 18.96%). Overall, primary union rate was 87.1%. Subsequent flap fracture rate was 3.3%. There were only two (0.6%) VBF losses reported in the included cases, and donor-site complications were similarly rare (17, 4.7%). CONCLUSION: VBF reconstruction is often utilized for postoncologic defects and recalcitrant nonunions. The fibula is the most utilized VBF, but the medial femoral condyle flap is used frequently for smaller defects. VBF reconstruction demonstrates high union rates and low flap fracture rate across indications.

9.
Ann Surg ; 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38482684

RESUMEN

OBJECTIVE: To evaluate whether a machine learning algorithm (i.e. the "NightSignal" algorithm) can be used for the detection of postoperative complications prior to symptom onset after cardiothoracic surgery. SUMMARY BACKGROUND DATA: Methods that enable the early detection of postoperative complications after cardiothoracic surgery are needed. METHODS: This was a prospective observational cohort study conducted from July 2021 to February 2023 at a single academic tertiary care hospital. Patients aged 18 years or older scheduled to undergo cardiothoracic surgery were recruited. Study participants wore a Fitbit watch continuously for at least 1 week preoperatively and up to 90-days postoperatively. The ability of the NightSignal algorithm-which was previously developed for the early detection of Covid-19-to detect postoperative complications was evaluated. The primary outcomes were algorithm sensitivity and specificity for postoperative event detection. RESULTS: A total of 56 patients undergoing cardiothoracic surgery met inclusion criteria, of which 24 (42.9%) underwent thoracic operations and 32 (57.1%) underwent cardiac operations. The median age was 62 (IQR: 51-68) years and 30 (53.6%) patients were female. The NightSignal algorithm detected 17 of the 21 postoperative events a median of 2 (IQR: 1-3) days prior to symptom onset, representing a sensitivity of 81%. The specificity, negative predictive value, and positive predictive value of the algorithm for the detection of postoperative events were 75%, 97%, and 28%, respectively. CONCLUSIONS: Machine learning analysis of biometric data collected from wearable devices has the potential to detect postoperative complications-prior to symptom onset-after cardiothoracic surgery.

10.
Head Neck ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38488221

RESUMEN

BACKGROUND: We analyzed online rating scores and comments of head and neck surgeons to understand factors that contribute to higher ratings. METHODS: Numerical ratings and comments for American Head and Neck Society physicians were extracted from Healthgrades, Vitals, RateMDs, and Yelp, with narrative comments categorized based on content. Physician practice location, education, and residency training were also compiled. RESULTS: Patient ratings were significantly higher with supportive staff and affable physician demeanor but showed significant drops with longer wait times and difficulties scheduling appointments or follow-ups. Physician education and postgraduate training did not significantly affect ratings. CONCLUSION: Online ratings and comments correlated to modifiable factors in clinical practice and may be informative in understanding patient needs.

11.
Plast Reconstr Surg Glob Open ; 12(3): e5668, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38510327

RESUMEN

Background: The T-line hernia mesh is a synthetic, polypropylene mesh specifically designed to prevent anchor point failure by evenly distributing tension through mesh suture extensions. This case series illustrates the first clinical application of the T-line mesh for umbilical hernia repair (UHR). Methods: This study is a retrospective, consecutive cases series of all adult patients presenting to a single surgeon with symptomatic umbilical hernia requiring surgical repair using the T-line hernia mesh. Patient demographics, surgical details, and 30-day postoperative complications were collected. Descriptive statistics were computed in Microsoft Excel (Redmond, Va.). Results: Three patients presented for UHR. All three patients were obese with mean body mass index of 37.5 ±â€…6.6. Two patients were former smokers, and two had presented after hernia recurrence. The average defect size was 80.1 cm2 ± 94.0 cm2. Two patients had UHR with onlay mesh placement, whereas one had a transversus abdominus release followed by retrorectus mesh placement. The average mesh size was 192.3 cm2 ± 82.5 cm2. All three cases were classified as clean. There were no intraoperative complications. No patients experienced 30-day postoperative complications or recurrence. Conclusions: We present a case series of three patients presenting with large, symptomatic umbilical hernias who underwent UHR with T-line hernia mesh reinforcement without short term complications or hernia recurrence at last follow-up.

12.
Work ; 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38306085

RESUMEN

BACKGROUND: The COVID-19 pandemic caused notable shifts in healthcare behavior, influenced by remote work policies. This study examines the impact of Work from Home (WFH) policies on public interest in ankle-related orthopaedic surgeries, utilizing Google search trends. Understanding these trends is crucial for healthcare providers, enabling them to adapt services and communication to evolving patient needs during challenging times. OBJECTIVE: To comprehend variations in search volume and trends for ankle-related queries due to WFH policies during the COVID-19 pandemic. METHODS: Ankle-related terms accessible to laypersons were analyzed using Google Trends data from March 2018 to March 2022 in the United States. Data were divided into pre-pandemic (March 2018-March 2020) and post-pandemic (March 2020-March 2022) periods. Weekly search interest data for 20 terms were analyzed using a Mann-Whitney U test. The study aimed to identify significant changes in search interest, providing insights into public information-seeking behavior concerning ankle surgeries. RESULTS: Among the 20 terms analyzed, 11 exhibited significant changes. Ankle arthritis and ankle bursitis showed increased interest, suggesting heightened concern during the pandemic. Conversely, post-pandemic interest decreased for terms 9 terms, including ankle pain and ankle tendonitis, indicating reduced worry. Moderate declines were noted for ankle gout, Achilles tendonitis, and heel bursitis, reflecting shifting patient priorities. Some terms, including ankle fracture and ankle arthroplasty, showed stable information-seeking behavior despite the pandemic. CONCLUSIONS: The study underscores the nuanced impact of WFH policies on public interest in ankle-related orthopaedic surgeries. Varied search trends highlight changing patient concerns. Healthcare providers can use these insights to tailor services effectively, meeting evolving patient needs and enhancing communication strategies.

13.
Radiother Oncol ; 192: 110090, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38224916

RESUMEN

BACKGROUND AND PURPOSE: The SOFT trial is a prospective, multicenter, phase 2 trial investigating magnetic resonance (MR)-guided stereotactic ablative radiotherapy (SABR) for abdominal, soft tissue metastases in patients with oligometastatic disease (OMD) (clinicaltrials.gov ID NCT04407897). We present the primary endpoint analysis of 1-year treatment-related toxicity (TRAE). MATERIALS AND METHODS: Patients with up to five oligometastases from non-hematological cancers were eligible for inclusion. A risk-adapted strategy prioritized fixed organs at risk (OAR) constraints over target coverage. Fractionation schemes were 45-67.5 Gy in 3-8 fractions. The primary endpoint was grade ≥ 4 TRAE within 12 months post-SABR. The association between the risk of gastrointestinal (GI) toxicity and clinical and dosimetric parameters was tested using a normal tissue complication probability model. RESULTS: We included 121 patients with 147 oligometastatic targets, mainly located in the liver (41 %), lymph nodes (35 %), or adrenal glands (14 %). Nearly half of all targets (48 %, n = 71) were within 10 mm of a radiosensitive OAR. No grade 4 or 5 TRAEs, 3.5 % grade 3 TRAEs, and 43.7 % grade 2 TRAEs were reported within the first year of follow-up. We found a significant association between grade ≥ 2 GI toxicity and the parameters GI OAR D0.1cc, D1cc, and D20cc. CONCLUSION: In this phase II study of MR-guided SABR of oligometastases in the infra-diaphragmatic region, we found a low incidence of toxicity despite half of the lesions being within 10 mm of a radiosensitive OAR. GI OAR D0.1cc, D1cc, and D20cc were associated with grade ≥ 2 GI toxicity.


Asunto(s)
Neoplasias , Radiocirugia , Humanos , Estudios Prospectivos , Fraccionamiento de la Dosis de Radiación , Radiocirugia/efectos adversos
14.
Pain Pract ; 24(1): 76-81, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37606504

RESUMEN

INTRODUCTION: Kyphoplasty is a minimally invasive treatment for chronic refractory pain secondary to spinal compression fracture. This study investigates racial and socioeconomic disparities in kyphoplasty among the Medicare population. MATERIALS AND METHODS: This study utilized data from the Medicare Limited Data Sets (LDS), a CMS administrative claims database. Patients aged 18 and older with ICD code consistent with spinal pathology and compression fractures were included. Outcome was defined as kyphoplasty by race and socioeconomic status (SES) with low SES defined by dual enrollment in Medicare/Medicaid. RESULTS: There was a total of 215,502 patients gathered from CMS data, and 717 (0.33%) of these patients underwent kyphoplasty during the study period. Of these patients, 458 (63.8%) were female, the average age was 76.5 years old, 655 (91.3%) were White, 20 (2.7%) were Black, 9 (1.3%) were Hispanic, and 98 (13.7%) were Medicare/Medicaid dual eligible. White patients (32,317/157,177 [20.6%]) were less likely to be dual enrollment eligible in Medicare and Medicaid than Black (5407/13,522 [39.9%]), Hispanic (2833/3675 [77.1%]), Asian (2087/3312 [63.0%]), or North American Native patients (778/1578 [49.1%]). Multivariate regression (MVR) analysis was performed and showed that Blacks were less likely than Whites to have a kyphoplasty performed (OR 0.46 [95% CI: 0.29-0.72], p-value <0.001). Although Hispanics (OR 0.95 [0.49-1.86]), North American Native (OR 0.82 [0.3-2.19]), and unknown race had a decreased odd of undergoing kyphoplasty, it was not statistically significant. CONCLUSION: Our study showed after adjustment for pertinent comorbidities, Medicare/Medicaid dual-eligible patients and Black patients were significantly less likely to receive kyphoplasty than White patients with Medicare.


Asunto(s)
Cifoplastia , Medicare , Grupos Raciales , Disparidades Socioeconómicas en Salud , Anciano , Femenino , Humanos , Masculino , Medicaid , Estados Unidos/epidemiología
15.
Radiother Oncol ; 191: 110064, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38135187

RESUMEN

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity. MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose10 [BED10] = 100 Gy). Elective coverage was optional. Surgery and chemotherapy were permitted after SMART. RESULTS: Mean age was 65.7 years (range, 36-85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively. CONCLUSIONS: Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted.


Asunto(s)
Neoplasias Pancreáticas , Radiocirugia , Humanos , Anciano , Neoplasias Pancreáticas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Planificación de la Radioterapia Asistida por Computador , Radiocirugia/efectos adversos
16.
J Thorac Cardiovasc Surg ; 167(1): 350-364.e17, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37473997

RESUMEN

OBJECTIVE: The study objective was to identify whether the results of JCOG0802 could be generalized to US clinical settings. METHODS: Patients diagnosed with clinical stage IA (≤2 cm) non-small cell lung cancer who underwent segmentectomy versus lobectomy (2004-2017) in the National Cancer Database were identified. Overall survival of patients in the National Cancer Database was assessed using propensity score-matched analysis. A separate analysis of the Surveillance Epidemiology End Results database was conducted to evaluate treatment patterns of second primary lung cancers among patients who underwent segmentectomy versus lobectomy for a first primary lung cancer. RESULTS: Of the 23,286 patients in the National Cancer Database meeting inclusion criteria, 1397 (6.0%) underwent segmentectomy and 21,889 (94.0%) underwent lobectomy. In a propensity score-matched analysis of all patients in the study cohort, there were no significant differences in overall survival between patients undergoing segmentectomy versus lobectomy (5-year overall survival: 79.9% [95% CI, 76.7%-82.0%] vs 81.8% [95% CI, 78.7%-84.4%], log-rank: P = .72). In subgroup analyses by tumor grade and histologic subtype, segmentectomy was associated with similar overall survival compared with lobectomy in all subgroups evaluated. In a propensity score-matched analysis of patients in the Surveillance Epidemiology End Results database, there were no significant differences in treatment patterns of second primary lung cancers between patients who underwent segmentectomy and patients who underwent lobectomy for their first primary lung cancer. CONCLUSIONS: In this national analysis of US patients diagnosed with stage IA (≤2 cm) non-small cell lung cancer, there were no significant differences in overall survival between segmentectomy and lobectomy in the overall cohort or in subgroup analyses by tumor grade or histologic subtype.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Primarias Secundarias , Humanos , Estados Unidos/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Neumonectomía/métodos , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/cirugía , Neoplasias Primarias Secundarias/patología , Estudios Retrospectivos
17.
Semin Radiat Oncol ; 34(1): 129-134, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38105087

RESUMEN

The introduction of MR-guided treatment machines into the radiation oncology clinic has provided unique challenges for the radiotherapy QA program. These MR-linac systems require that existing QA procedures be adapted to verify linac performance within the magnetic field environment and that new procedures be added to ensure acceptable image quality for the MR system. While both high and low-field MR-linac options exist, this chapter is intended to provide a structure for implementing a QA program within the low-field MR environment. This review is divided into three sections. The first section focuses on machine QA tasks including mechanical and dosimetric verification. The second section is concentrated on the procedures implemented for imaging QA. Finally, the last section covers patient specific QA tasks including special considerations related to the performance of patient specific QA within the framework of online adaptive radiotherapy.


Asunto(s)
Aceleradores de Partículas , Radioterapia Guiada por Imagen , Humanos , Imagen por Resonancia Magnética/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Radiometría
18.
J Biol Chem ; 299(12): 105435, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37944620

RESUMEN

Copper is essential for all eukaryotic cells but many details of how it is trafficked within the cell and how it is homeostatically regulated remain uncertain. Here, we characterized the copper content of cytosol and mitochondria using liquid chromatography with ICP-MS detection. Chromatograms of cytosol exhibited over two dozen peaks due to copper proteins and coordination complexes. Yeast cells respiring on minimal media did not regulate copper import as media copper concentration increased; rather, they imported copper at increasing rates while simultaneously increasing the expression of metallothionein CUP1 which then sequestered most of the excessive imported copper. Peak intensities due to superoxide dismutase SOD1, other copper proteins, and numerous coordination complexes also increased, but not as drastically. The labile copper pool was unexpectedly diverse and divided into two groups. One group approximately comigrated with copper-glutathione, -cysteine, and -histidine standards; the other developed only at high media copper concentrations and at greater elution volumes. Most cytosolic copper arose from copper-bound proteins, especially CUP1. Cytosol contained an unexpectedly high percentage of apo-copper proteins and apo-coordination complexes. Copper-bound forms of non-CUP1 proteins and complexes coexisted with apo-CUP1 and with the chelator BCS. Both experiments suggest unexpectedly stable-binding copper proteins and coordination complexes in cytosol. COX17Δ cytosol chromatograms were like those of WT cells. Chromatograms of soluble mitochondrial extracts were obtained, and mitoplasting helped distinguish copper species in the intermembrane space versus in the matrix/inner membrane. Issues involving the yeast copperome, copper homeostasis, labile copper pool, and copper trafficking are discussed.


Asunto(s)
Complejos de Coordinación , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Cobre/metabolismo , Complejos de Coordinación/metabolismo , Proteínas Portadoras/metabolismo , Homeostasis , Metalotioneína/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
19.
Transl Vis Sci Technol ; 12(10): 18, 2023 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-37889504

RESUMEN

Glaucoma is the leading cause of irreversible blindness worldwide, currently affecting around 80 million people. Glaucoma prevalence is rapidly rising in the United States due to an aging population. Despite recent advances in the diagnosis and treatment of glaucoma, significant disparities persist in disease detection, management, and outcomes among the diverse patient populations of the United States. Research on disparities is critical to identifying, understanding, and addressing societal and healthcare inequalities. Disparities research is especially important and impactful in the context of irreversible diseases such as glaucoma, where earlier detection and intervention are the primary approach to improving patient outcomes. In this article, we first review recent studies identifying disparities in glaucoma care that affect patient populations based on race, age, and gender. We then review studies elucidating and furthering our understanding of modifiable factors that contribute to these inequities, including socioeconomic status (particularly age and education), insurance product, and geographic region. Finally, we present work proposing potential strategies addressing disparities in glaucoma care, including teleophthalmology and artificial intelligence. We also discuss the presence of non-modifiable factors that contribute to differences in glaucoma burden and can confound the detection of glaucoma disparities. Translational Relevance: By recognizing underlying causes and proposing potential solutions, healthcare providers, policymakers, and other stakeholders can work collaboratively to reduce the burden of glaucoma and improve visual health and clinical outcomes in vulnerable patient populations.


Asunto(s)
Glaucoma , Oftalmología , Telemedicina , Humanos , Estados Unidos/epidemiología , Anciano , Inteligencia Artificial , Glaucoma/diagnóstico , Glaucoma/epidemiología , Glaucoma/terapia , Disparidades en Atención de Salud
20.
J Cardiovasc Electrophysiol ; 34(11): 2225-2232, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37702135

RESUMEN

INTRODUCTION: The need for pacemaker is a common complication after transcatheter aortic valve replacement (TAVR). We previously described the Emory Risk Score (ERS) to predict the need for new pacemaker implant (PPM) after TAVR. Metrics included in the score are a history of syncope, pre-existing RBBB, QRS duration ≥140 ms, and prosthesis oversizing ≥16%. To prospectively validate the previously described risk score. METHODS: We prospectively evaluated all patients without pre-existing pacemakers, ICD, or pre-existing indications for pacing undergoing TAVR with the Edwards SAPIEN 3 prosthesis at our institution from March 2019 to December 2020 (n = 661). Patients were scored prospectively; however, results were blinded from clinical decision-making. The primary endpoint was PPM at 30 days after TAVR. Performance of the ERS was evaluated using logistic regression, a calibration curve to prior performance, and receiver operating characteristic (ROC) analysis. RESULTS: A total of 48 patients (7.3%) had PPM after TAVR. A higher ERS predicted an increased likelihood of PPM (OR 2.61, 95% CI: 2.05-3.25 per point, p < 0.001). There was good correlation between observed and expected values on the calibration curve (slope = 1.04, calibration at large = 0.001). The area under the ROC curve was 0.81 (95% CI [0.74-0.88], p < 0.001). CONCLUSIONS: The ERS prospectively predicted the need for PPM in a serial, real-world cohort of patients undergoing TAVR with a balloon-expandable prosthesis, confirming findings previously described in retrospective cohorts. Notably, the prospective performance of the score was comparable with that of the initial cohorts. The risk score could serve as a framework for preprocedural risk stratification for PPM after TAVR.


Asunto(s)
Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Marcapaso Artificial , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Estudios Retrospectivos , Estimulación Cardíaca Artificial/efectos adversos , Estimulación Cardíaca Artificial/métodos , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Resultado del Tratamiento , Factores de Riesgo , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía
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