Citations

Background: The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the available literature is needed to evaluate the efficacy of this approach. Methods: We comprehensively searched electronic databases using MeSH terms related to skull defects, bone marrow mesenchymal stem cells, and bone morphogenic proteins. Eligible studies included animal studies that used BMP therapy and mesenchymal stem cells to promote bone regeneration in calvarial defects. Reviews, conference articles, book chapters, and non-English language studies were excluded. Two independent investigators conducted the search and data extraction. Results: Twenty-three studies published between 2010 and 2022 met our inclusion criteria after a full-text review of the forty-five records found in the search. Eight of the 23 studies used mice as models, while 15 used rats. The most common mesenchymal stem cell was bone marrow-derived, followed by adipose-derived. BMP-2 was the most popular. Stem cells were embedded in Scaffold (13), Transduction (7), and Transfection (3), and they were delivered BMP to cells. Each treatment used 2 × 104–1 × 107 mesenchymal stem cells, averaging 2.26 × 106. Most BMP-transduced MSC studies used lentivirus. Conclusions: This systematic review examined BMP and MSC synergy in biomaterial scaffolds or alone. BMP therapy and mesenchymal stem cells in calvarial defects, alone, or with a scaffold regenerated bone. This method treats skull defects in clinical trials. The best scaffold material, therapeutic dosage, administration method, and long-term side effects need further study.

Background: Multiple myeloma (MM) is the second most common hematologic malignancy, with 34,470 estimated new cases in 2022. High-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) remains a standard treatment for MM even in the era of novel therapies. This is usually performed in hospital-based settings, either in the inpatient or outpatient units. Advanced Care at Home (ACH) represents a virtual hybrid hospital-at-home program that combines a virtual provider-staffed command center with a vendor-mediated supply chain capable of delivering high-acuity care in the comfort of the patients’ own homes. In our program, we used the existing ACH platform to deliver post-HCT care for recipients of auto-HCT. Patients and methods: Four patients (female = 2, 50%) with MM, with a median age of 60 (range, 40–74) years, were admitted to the inpatient Blood and Marrow Transplant (BMT) unit. The conditioning regimen consisted of melphalan 200 mg/m 2 , administered on day –2. All patients received stem cell infusion (day 0) in the inpatient setting, with a median dose of 3.64 (range, 2.92–8.22) × 10 6 /kg CD34 cells. Results: Patients were discharged to their homes after completing the infusion on day 0 or day +1 at the latest. Postinfusion care was provided by the ACH team in coordination with the BMT team. The median time intervals to absolute neutrophil count and platelet engraftment were 12 (range, 11–13) and 11 (range, 9–16) days, respectively. All patients were successfully discharged from the ACH program at a median of day +14 (range, day +14 to day +15). Conclusions: Our results highlight the feasibility of delivering post-HCT care for auto-HCT recipients in the home setting and confirm the generalizability of this approach.

505 Background: Increased TILs are associated with better prognosis in triple-negative BC, including in patients (pts) age < 40. However, the role of TILs remains unclear in HR+/HER2- BC and little data exist in young pts, in whom immune microenvironment could be altered by age-related host/tumor differences. We assessed the extent and composition of immune infiltration in HR+ tumors of young women and correlated with clinicopathologic features and survival outcomes. Methods: From a prospective cohort study of women with BC diagnosed age ≤40, we identified those with stage I-III HR+/HER2- BC and available pre-treatment (tx) tumor tissue. Multiplexed immunofluorescence was used to quantify cytotoxic T (CD8+), T helper (Th, CD3+CD8-), T regulatory (Tregs, FOXP3+CD3+) and exhausted T (PD1+CD8+) cells in stroma and tumor. Univariate analyses tested associations between clinicopathologic variables and immune markers by high or low expression, divided based on median. High vs. low TILs were evaluated in Cox regression analyses for invasive breast cancer-free survival (iBCFS), distant disease-free survival (DDFS) and overall survival (OS). Results: In 390 pts, median age was 37 years (21-40), most had grade 2 (51%), T1 (65%), N0 (63%) tumors and 67% received adjuvant chemotherapy. Black pts (n = 17) had higher expression of stromal CD8+ ( P= .010), FOXP3+CD3+ ( P= .027) and PD1+CD8+ TILs ( P= .043); intratumoral TILs did not differ by race. Older age (36-40) was associated with high expression of CD8+ ( P= .033) and PD1+CD8+ TILs ( P= .031) within stroma and CD3+CD8- TILs within tumor ( P= .046). Grade 3 tumors had higher stromal and intratumoral expression of CD3+CD8- ( P= .002; P< .001) and FOXP3+CD3+ TILs ( P= .020; P< .001). No differences in TILs were seen according to recency of pregnancy, BRCA1/2 status or T/N stage. Over a median follow up of 8 years, 85 iBCFS events, 64 DDFS events and 37 deaths occurred. High stromal expression of CD3+CD8- TILs was associated with better iBCFS (HR 0.49, P= .002) and DDFS (HR 0.57, P= .046), which remained significant when adjusted for T/N stage, grade and chemotherapy (iBCFS HR 0.41, P< .001; DDFS HR 0.45, P= .008). High stromal expression of CD3+CD8- and FOXP3+CD3+ TILs was associated with better OS (HR 0.47, P= .038) and iBCFS (HR 0.58, P= .018), respectively, on adjusted analyses only. High intratumoral expression of CD3+CD8- and FOXP3+CD3+ TILs was associated with better iBCFS (HR 0.59, P= .025; HR 0.63, P= .043) after adjustment only. Conclusions: The distribution of TIL subtypes in young women’s HR+ BC varied according to race, age and grade. High stromal and intratumoral expression of Th and Tregs was associated with improved BC outcomes. Characterization of immune cell subsets could help refine the prognostic value of TILs in HR+ BC, particularly in young pts who may benefit from individualized escalated/de-escalated tx strategies.

In recent years, the endoscopic endonasal approach (EEA) for craniopharyngiomas has proven to be a safe option for extensive tumor resection, with minimal or no manipulation of the optic nerves and excellent visualization of the superior hypophyseal branches when compared to the Transcranial Approach (TCA). However, there is an ongoing debate regarding the criteria for selecting different approaches. To explore the current results of EEA and discuss its role in the management of craniopharyngiomas, we performed MEDLINE, Embase, and LILACS searches from 2012 to 2022. Baseline characteristics, the extent of resection, and clinical outcomes were evaluated. Statistical analysis was performed through an X2 and Fisher exact test, and a comparison between quantitative variables through a Kruskal–Wallis and verified with post hoc Bonferroni. The tumor volume was similar in both groups (EEA 11.92 cm3, -TCA 13.23 cm3). The mean follow-up in months was 39.9 for EEA and 43.94 for TCA, p = 0.76). The EEA group presented a higher visual improvement rate (41.96% vs. 25% for TCA, p < 0.0001, OR 7.7). Permanent DI was less frequent with EEA (29.20% vs. 67.40% for TCA, p < 0.0001, OR 0.2). CSF Leaks occurred more frequently with EEA (9.94% vs. 0.70% for TCA, p < 0.0001, OR 15.8). Recurrence rates were lower in the EEA group (EEA 15.50% vs. for TCA 21.20%, p = 0.04, OR 0.7). Our results demonstrate that, in selected cases, EEA for resection of craniopharyngiomas is associated with better results regarding visual preservation and extent of tumor resection. Postoperative CSF leak rates associated with EEA have improved compared to the historical series. The decision-making process should consider each person’s characteristics; however, it is noticeable that recent data regarding EEA justify its widespread application as a first-line approach in centers of excellence for skull base surgery.

AbstractCardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Pain assessment is a complex task largely dependent on the patient’s self-report. Artificial intelligence (AI) has emerged as a promising tool for automating and objectifying pain assessment through the identification of pain-related facial expressions. However, the capabilities and potential of AI in clinical settings are still largely unknown to many medical professionals. In this literature review, we present a conceptual understanding of the application of AI to detect pain through facial expressions. We provide an overview of the current state of the art as well as the technical foundations of AI/ML techniques used in pain detection. We highlight the ethical challenges and the limitations associated with the use of AI in pain detection, such as the scarcity of databases, confounding factors, and medical conditions that affect the shape and mobility of the face. The review also highlights the potential impact of AI on pain assessment in clinical practice and lays the groundwork for further study in this area.

Pain is a complex and subjective experience, and traditional methods of pain assessment can be limited by factors such as self-report bias and observer variability. Voice is frequently used to evaluate pain, occasionally in conjunction with other behaviors such as facial gestures. Compared to facial emotions, there is less available evidence linking pain with voice. This literature review synthesizes the current state of research on the use of voice recognition and voice analysis for pain detection in adults, with a specific focus on the role of artificial intelligence (AI) and machine learning (ML) techniques. We describe the previous works on pain recognition using voice and highlight the different approaches to voice as a tool for pain detection, such as a human effect or biosignal. Overall, studies have shown that AI-based voice analysis can be an effective tool for pain detection in adult patients with various types of pain, including chronic and acute pain. We highlight the high accuracy of the ML-based approaches used in studies and their limitations in terms of generalizability due to factors such as the nature of the pain and patient population characteristics. However, there are still potential challenges, such as the need for large datasets and the risk of bias in training models, which warrant further research.

Unnecessary ED visits and transfers to hand clinics raise treatment costs and patient burden at trauma centers. In the present COVID-19 pandemic, needless transfers can increase patients’ risk of viral exposure. Therefore, this review analyzes different aspects of the remote diagnosis and triage of traumatic hand injuries. The most common file was photography, with the most common devices being cell phone cameras. Treatment, triage, diagnosis, cost, and time outcomes were assessed, showing concordance between teleconsultation and face-to-face patient evaluations. We conclude that photography and video consultations are feasible surrogates for ED visits in patients with traumatic hand injuries. These technologies should be leveraged to decrease treatment costs and potentially decrease the time to definitive treatment after initial evaluation.

Background: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. Methods: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. Results: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70–11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower–middle versus high: odds ratio, 0.08 [95% CI, 0.04–0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07–5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84–4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70–9.42]) were significantly associated with increased odds of MTA. Conclusions: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country’s per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

Background Demographic characteristics are known to influence the treatment and outcomes of patients with invasive melanoma. Whether these characteristics influence treatment costs is unknown. We aimed to analyze whether patient demographics and tumor characteristics influence treatment costs for patients with invasive cutaneous melanoma in Florida. Methods This was a cross-sectional study in which the Florida Inpatient and Outpatient Dataset of the Agency for Health Care Administration was analyzed for patients with a diagnosis of invasive melanoma between January 1, 2013 and December 31, 2018. Categorical variables were assessed using Pearson χ2 tests, and continuous variables were evaluated using Kruskal-Wallis tests. Logistic regression analysis was conducted to identify the association between patient demographics and total costs. All analyses were done using SAS 9.4 statistical software (SAS Institute, Inc). Results Multivariate analysis showed that sex (P < 0.001), hospital setting (P < 0.001), race/ethnicity (P < 0.01), patient region (P < 0.01), Elixhauser Comorbidity Index score (P < 0.001), presence of metastasis (P < 0.01), total number of procedures (P < 0.001), and length of stay (P < 0.001) were correlated with the cost of treatment of invasive cutaneous melanoma. After stratification, the association between cost and race/ethnicity disappeared for inpatients but remained for Black patients in the outpatient setting (P < 0.001). The association between cost and patient residence regions also differed when the cohort was stratified. Conclusions Strategies addressing disparities in treatment cost of invasive melanoma should differ, depending on the hospital setting where the patient is being treated.