Irreversible electroporation (IRE) ablation is gaining popularity over the last decade as a nonthermal alternative to thermal ablation technologies such as radiofrequency ablation (RFA) and Microwave ablation (MWA). This review serves as a practical guide for applying IRE to colorectal cancer liver metastases (CRLM) for interventional radiologists, oncologists, surgeons, and anesthesiologists. It covers patient selection, procedural technique, anesthesia, imaging, and outcomes.
Introduction: Bonding to crystalline zirconia is currently a challenge. Properly cured adhesives are crucial to optimize this bond, and that in turn is influenced by the initial mobility of the system, as well as by the reactivity of the initiators. Aim: This study aimed to characterize adhesives containing monomer mixtures of different viscosities and double and triple photoinitiator systems; and to evaluate the bonding to Y-TZP zirconia, when adhesives were light-activated with monowave or polywave light-curing units (LCU). Materials and methods: Adhesives were formulated at a 1:1 weight proportion of Bis-GMA/TEGDMA or Bis-GMA/Bis-EMA. To these mixtures 0.5 wt% of CQ, 0.5-1.0 wt% of DABE, 0.5-1.0 wt% of DPIHP, or 0.5-1.0 wt% of TAS-Sb were added and used as photoinitiator systems. A total of ten adhesives were prepared. Resin composite cylinders were cemented on zirconia slices and 6000 thermal cycles were performed. Degree of conversion (DC), sorption (SO) and solubility (SL) after 7 days of water storage, and microshear bond strength (µSBS) were evaluated. Data were analyzed with three-way ANOVA and Tukey's HSD (α = 0.05). Results: Bis-GMA/Bis-EMA combined with either CQ/DABE or CQ/DABE/TAS-Sb presented the highest DC, and no significant differences were observed for LCUs (p = .298). CQ/DABE < CQ/DABE/TAS-Sb ≈ CQ/DABE/DPIHP and the polywave LCU showed smaller overall SO (p < .05). Bis-GMA/TEGDMA with CQ/DABE cured with the polywave LCU presented the lowest SO. SL varied as follows: CQ/DABE/TAS-Sb < CQ/DABE/DPIHP < CQ/DABE (p < .001). For µSBS, only the factor photoinitiator system was significant (p = .045). All mean values were above 30 MPa, with higher values being observed for BIS-GMA/TEGDMA and CQ/DABE. Conclusion: It can be concluded that the adhesive containing CQ/DABE/TAS-Sb as coinitiator of Bis-GMA/Bis-EMA mixtures produced a material with higher DC and lower SL, while bond strength values were similar to the ones obtained by CQ/DABE.
Previous research has identified unexpectedly strong associations between dyspnea and pain, but the reasons remain unclear. Ascertaining the underlying biological and psychological mechanisms might enhance the understanding of the experience of both conditions, and suggest novel treatments. We sought to elucidate whether demographic factors, disease severity, psychological symptoms and biomarkers might account for the association between pain and dyspnea in individuals with COPD. We analyzed data from 301 patients with COPD who were followed in a prospective longitudinal observational study over 2 years. Measures included self-reported dyspnea and pain, pulmonary function tests, serum levels of inflammatory cytokines, measures of physical deconditioning, and scales for depression and anxiety. Analyses involved cross-sectional and longitudinal linear regression models. Pain and dyspnea were strongly correlated cross-sectionally (r = 0.77, 95% CI 0.72-0.82) and simultaneously across time (r = 0.42, 95% CI 0.28-0.56). Accounting for any of the other health factors only slightly mitigated the associations. Symptoms of pain and dyspnea thus may be fundamentally linked in COPD, rather than being mediated by common biological, psychological, or functional factors. From the patient's perspective, pain and dyspnea may be part of the same essential experience. It is possible that treatments for one condition would improve the other.
Background: Addressing the opioid crisis requires an understanding of how to train both health professional students and practicing clinicians on medications for opioid use disorder (mOUD). We designed a robust evaluation instrument to assess the impact of training on perceived clinical knowledge in these different categories of learners. Methods: We enrolled 3rd and 4th year medical, physician assistant (PA), and nurse practitioner (NP) students, as well as practicing PAs, NPs, and physicians to undertake the Drug Addiction Treatment Act (DATA) Waiver Training for mOUD. We designed and implemented a cross-sectional survey to assess perceived change in clinical knowledge as a result of training in opioid use disorder and satisfaction with training. Results: Twenty-one MD/DO and 45 NP/PA students, and 24 practicing MD/DO and 27 NP/PAs completed the survey. Among health professional students (n = 66) and practicing clinicians (n =51), perceived clinical knowledge scores increased significantly (p < 0.001) for all 13 variables. Program evaluation scores for the buprenorphine waiver training were high with no statistical differences between students and practicing clinicians. Overall, the majority of participants indicated they would recommend the training to a colleague (Students' score = 4.84; practicing clinician scores = 4.53; scale = strongly disagree = 1 to strongly agree = 5). Conclusions: Our novel instrument allowed us to determine that the implementation of buprenorphine waiver trainings for health professional students and practicing clinicians leads to significant increases in perceived knowledge, interest and confidence in diagnosing and treating OUD. Although the buprenorphine waiver can now be obtained without training, many waivered providers still do not prescribe buprenorphine; integrating training into medical, NP, and PA curriculum for students and offering the training to practicing clinicians may increase confidence and uptake of mOUD.
Most cardiac imaging conferences have adopted social media as a means of disseminating conference highlights to a global audience well beyond the confines of the conference location. A deliberate and thoughtful social media campaign has the potential to increase the reach of the conference and allow for augmented engagement. The coronavirus disease 2019 (COVID-19) pandemic triggered a radical transformation in not just the delivery of healthcare but also the dissemination of science within the medical community. In the past, in-person medical conferences were an integral annual tradition for most medical professionals to stay up to date with the latest in the field. Social distancing requirements of the COVID-19 pandemic resulted in either cancelling medical conferences or shifting to a virtual format. Following suit, for the first time in its history, the 2021 Society for Cardiovascular Magnetic Resonance (SCMR) annual meeting was an all-virtual event. This called for a modified social media strategy which aimed to re-create the sociability of an in-person conference whilst also promoting global dissemination of the science being presented. This paper describes the employment of social media as well as the evolution through the SCMR scientific sessions for 2020 and 2021 that serves as a model for future cardiovascular conferences.
Background COVID-19 pandemic has a devastating impact on the economies and health care system of sub-Saharan Africa. Healthcare workers (HWs), the main actors of the health system, are at higher risk because of their occupation. Serology-based estimates of SARS-CoV-2 infection among HWs represent a measure of HWs’ exposure to the virus and could be used as a guide to the prevalence of SARS-CoV-2 in the community and valuable in combating COVID-19. This information is currently lacking in Ethiopia and other African countries. This study aimed to develop an in-house antibody testing assay, assess the prevalence of SARS-CoV-2 antibodies among Ethiopian high-risk frontline HWs. Methods We developed and validated an in-house Enzyme-Linked Immunosorbent Assay (ELISA) for specific detection of anti-SARS-CoV-2 receptor binding domain immunoglobin G (IgG) antibodies. We then used this assay to assess the seroprevalence among HWs in five public hospitals located in different geographic regions of Ethiopia. From consenting HWs, blood samples were collected between December 2020 and February 2021, the period between the two peaks of COVID-19 in Ethiopia. Socio-demographic and clinical data were collected using questionnaire-based interviews. Descriptive statistics and bivariate and multivariate logistic regression were used to determine the overall and post-stratified seroprevalence and the association between seropositivity and potential risk factors. Results Our successfully developed in-house assay sensitivity was 100% in serum samples collected 2- weeks after the first onset of symptoms whereas its specificity in pre-COVID-19 pandemic sera was 97.7%. Using this assay, we analyzed a total of 1997 sera collected from HWs. Of 1997 HWs who provided a blood sample, and demographic and clinical data, 51.7% were females, 74.0% had no symptoms compatible with COVID-19, and 29.0% had a history of contact with suspected or confirmed patients with SARS-CoV-2 infection. The overall seroprevalence was 39.6%. The lowest (24.5%) and the highest (48.0%) seroprevalence rates were found in Hiwot Fana Specialized Hospital in Harar and ALERT Hospital in Addis Ababa, respectively. Of the 821 seropositive HWs, 224(27.3%) of them had a history of symptoms consistent with COVID-19 while 436 (> 53%) of them had no contact with COVID-19 cases as well as no history of COVID-19 like symptoms. A history of close contact with suspected/confirmed COVID-19 cases is associated with seropositivity (Adjusted Odds Ratio (AOR) = 1.4, 95% CI 1.1–1.8; p = 0.015). Conclusion High SARS-CoV-2 seroprevalence levels were observed in the five Ethiopian hospitals. These findings highlight the significant burden of asymptomatic infection in Ethiopia and may reflect the scale of transmission in the general population.
Background: Patients report that familial support can facilitate initiation and maintenance of antiretroviral therapy (ART) and medications for opioid use disorder (MOUD). However, providing such support can create pressure and additional burdens for families of people with opioid use disorder (OUD) and HIV. We examined perspectives of people with HIV receiving treatment for OUD in Vietnam and their family members. Methods: Between 2015 and 2018, we conducted face-to-face qualitative interviews with 44 patients and 30 of their family members in Hanoi, Vietnam. Participants were people living with HIV and OUD enrolled in the BRAVO study comparing HIV clinic-based buprenorphine with referral to methadone treatment at 4 HIV clinics and their immediate family members (spouses or parents). Interviews were professionally transcribed, coded in Vietnamese, and analyzed using a semantic, inductive approach to qualitative thematic analysis. Results: Family members of people with OUD and HIV in Vietnam reported financially and emotionally supporting MOUD initiation and maintenance as well as actively participating in treatment. Family members described the burdens of supporting patients during opioid use, including financial costs and secondary stigma. Conclusions: Describing the role of family support in the lives of people living with OUD and HIV in the context of Vietnam enriches our understanding of their experiences and will support future treatment efforts targeting the family unit.
Background: The drug-related overdose crisis worsened during the COVID-19 pandemic. Recent drug policy changes to increase access to medications for opioid use disorder (MOUD) during COVID-19 shifted some outpatient MOUD treatment into virtual settings to reduce the demand for in-person care. The objective of this study was to qualitatively explore what is gained and lost in virtual patient encounters for patients with opioid use disorder at a low-threshold, addiction treatment clinic that offers buprenorphine and harm reduction services. Methods: Patients were included in this study if they received care at the Harm Reduction and BRidges to Care (HRBR) clinic and utilized virtual visits between November 2019 and March 2021. The study was conceptualized using a health care access framework and prior studies of telemedicine acceptability. Semi-structured interviews were completed between March and April 2021. Interviews were dual-coded and analyzed using directed content analysis. Results: Nineteen interviews were conducted. The sample was predominantly White (84%) and stably housed (79%) with comparable gender (male, 53%) and employment status (employed, 42%). The majority (63%) of patients preferred virtual visits compared to in-person visits (16%) or a combination of access to both (21%). Two overarching tandem domains emerged: availability-accommodation and acceptability-appropriateness. Availability-accommodation reflected participants' desires for immediate services and reduced transportation and work or caregiving scheduling barriers, which was facilitated by virtual visits. The acceptable-appropriate domain articulated how participants felt connected to their providers, whether through in-person interactions or the mutual trust experienced during virtual visits. Conclusions: Virtual visits were perceived by participants as a valuable and critical option for accessing treatment for OUD. While many participants preferred virtual visits, some favored face-to-face visits due to relational and physical interactions with providers. Participants desired flexibility and the ability to have a choice of treatment modality depending on their needs.
Germline mutations in BRCA1 or BRCA2 exist in ~2–7% of breast cancer patients, which has led to the approval of PARP inhibitors in the advanced setting. We have previously reported a phase II neoadjuvant trial of single agent talazoparib for patients with germline BRCA pathogenic variants with a pathologic complete response (pCR) rate of 53%. As nearly half of the patients treated did not have pCR, better strategies are needed to overcome treatment resistance. To this end, we conducted multi-omic analysis of 13 treatment naïve breast cancer tumors from patients that went on to receive single-agent neoadjuvant talazoparib. We looked for biomarkers that were predictive of response (assessed by residual cancer burden) after 6 months of therapy. We found that all resistant tumors exhibited either the loss of SHLD2, expression of a hypoxia signature, or expression of a stem cell signature. These results indicate that the deep analysis of pre-treatment tumors can identify biomarkers that are predictive of response to talazoparib and potentially other PARP inhibitors, and provides a framework that will allow for better selection of patients for treatment, as well as a roadmap for the development of novel combination therapies to prevent emergence of resistance.
Mitochondrial diseases are a group of rare, heterogeneous diseases caused by gene mutations in both nuclear and mitochondrial genomes that result in defects in mitochondrial function. They are responsible for significant morbidity and mortality as they affect multiple organ systems and particularly those with high energy-utilizing tissues, such as the nervous system, skeletal muscle, and cardiac muscle. Virtually no effective treatments exist for these patients, despite the urgent need. As the majority of these conditions are monogenic and caused by mutations in nuclear genes, gene replacement is a highly attractive therapeutic strategy. Adeno-associated virus (AAV) is a well-characterized gene replacement vector, and its safety profile and ability to transduce quiescent cells nominates it as a potential gene therapy vehicle for several mitochondrial diseases. Indeed, AAV vector-based gene replacement is currently being explored in clinical trials for one mitochondrial disease (Leber hereditary optic neuropathy) and preclinical studies have been published investigating this strategy in other mitochondrial diseases. This review summarizes the preclinical findings of AAV vector-based gene replacement therapy for mitochondrial diseases including Leigh syndrome, Barth syndrome, ethylmalonic encephalopathy, and others.
Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier : NCT00628745.
Background Despite demonstrated efficacy, medication treatment for opioid use disorder (MOUD) remain inaccessible to many patients, with barriers identified at the individual, clinic and system level. A wide array of implementation strategies have guided efforts to expand access to MOUD, with most centered around externally-facilitated approaches to practice change. While effective, such approaches may be inaccessible to those clinics and systems that lack the resources necessary to partner with an external team, suggesting a need to identify and describe change-processes that are internally developed and promoted. Methods Guided by the Consolidated Framework for Implementation Research (CFIR), we utilized qualitative interviews and ethnographic observation to investigate the planning, design and implementation of a locally-initiated process to expand access to MOUD within one health care system. All study documents were coded by a primary coder and secondary reviewer using a codebook designed for use with the CFIR. To analyze data, we reviewed text tagged by key codes, compared these textual excerpts both across and within documents, and organized findings into themes. Processes identified were mapped to established implementation science constructs and strategies. Results Interviews with clinicians and administrators (n = 9) and ethnographic observation of planning meetings (n = 3) revealed how a self-appointed local team developed, established broad support for, and successfully implemented a Primary Care-based Buprenorphine Clinic and E-Consult Service to expand access to MOUD to patients across the health care system. First, national and local policy changes—including altered clinical practice guidelines, performance pay incentives regarding opioid prescribing, and a directive from VA Central Office increased individual staff and administrators’ perception of the need for change and willingness to invest time and resources. Then, a self-appointed interdisciplinary team utilized cross-clinic meetings and information gathering to identify appropriate, and widely supported, models of care delivery and care consultation. Finally, the team increased staff investment in these change efforts by bringing them into the planning process and encouraging collaborative problem solving. Conclusions This study reveals how a local team developed and built widespread support for new processes of care that were tailored to local needs and well-positioned for sustainability over time.
Society for Cardiovascular Magnetic Resonance/European Society of Cardiovascular Imaging/American Society of Echocardiography/Society for Pediatric Radiology/North American Society for Cardiovascular Imaging Guidelines for the use of cardiovascular magnetic resonance in pediatric congenital and acquired heart disease: Endorsed by The American Heart Association
Cardiovascular magnetic resonance (CMR) has been utilized in the management and care of pediatric patients for nearly 40 years. It has evolved to become an invaluable tool in the assessment of the littlest of hearts for diagnosis, pre-interventional management and follow-up care. Although mentioned in a number of consensus and guidelines documents, an up-to-date, large, stand-alone guidance work for the use of CMR in pediatric congenital 36 and acquired 35 heart disease endorsed by numerous Societies involved in the care of these children is lacking. This guidelines document outlines the use of CMR in this patient population for a significant number of heart lesions in this age group and although admittedly, is not an exhaustive treatment, it does deal with an expansive list of many common clinical issues encountered in daily practice.
Introduction The use of the robot in general surgery has exploded in the last decade. The Veterans Health Administration presents a unique opportunity to study differences between surgical approaches due to the ability to control for health system and insurance variability. This study compares clinical outcomes between robot-assisted and laparoscopic or open techniques for three general surgery procedures. Methods A retrospective observational study using the Veterans Affair Surgical Quality Improvement Program database. Operative time, length of stay, and complications were compared for cholecystectomy (robot-assisted versus laparoscopic), ventral, and inguinal hernia repair (robot-assisted versus laparoscopic or open) from 2015 to 2019. Results More than 80,000 cases were analyzed (21,652 cholecystectomy, 9214 ventral hernia repairs, and 51,324 inguinal hernia repairs). Median operative time was longer for all robot-assisted approaches as compared to laparoscopic or open techniques with the largest difference seen between open and robot-assisted primary ventral hernia repair (unadjusted difference of 93 min, P < 0.001). Median length of stay was between 1 and 4 d and significantly for robot-assisted ventral hernia repairs (versus open, P < 0.01; versus lap for recurrent hernia, P < 0.05). Specific postoperative outcomes of interest were overall low with few differences between techniques. Conclusions While the robotic platform was associated with longer operative time, these findings must be interpreted in the context of a learning curve and indications for use (i.e., use of the robot for technically challenging cases). Our findings suggest that at the Veterans Health Administration, the robot is as safe a platform for common general surgery procedures as traditional approaches. Future studies should focus on patient-centered outcomes including pain and cosmesis.
Purpose Studies of early depth of sedation in mixed critically ill populations have suggested benefit to light sedation; however, the relationship of early depth of sedation with outcomes in patients with acute respiratory distress syndrome (ARDS) is unknown. Materials and methods We performed a propensity-score matched analysis of early light sedation (Richmond Agitation Sedation Scale Score, RASS 0 to −1 or equivalent) versus deep sedation (RASS −2 or lower) in patients enrolled in the non-intervention group of The Reevaluation of Systemic Early Neuromuscular Blockade trial. Primary outcome was 90 day mortality. Secondary outcomes included days free of mechanical ventilation, days not in ICU, days not in hospital at day 28. Results 137 of 486 participants (28.2%) received early light sedation. Vasopressor usage and Apache III scores significantly differed between groups. Prior to matching, 90-day mortality was higher in the early deep sedation (45.3%) compared to light sedation (34.2%) group. In the propensity score matched cohort, there was no difference in 90-day mortality (Odds Ratio (OR) 0.72, 95% CI 0.41, 1.27, p = 0.26) or secondary outcomes between the groups. Conclusions We did not find an association between early depth of sedation and clinical outcomes in this cohort of patients with moderate-to-severe ARDS.
Recent studies in cancer patients and animal models demonstrate that intestinal microbiota influence the therapeutic efficacy of cancer treatments, including immune checkpoint inhibition. However, no studies to-date have investigated relationships between gastrointestinal microbiota composition and response to checkpoint inhibition in advanced metastatic castrate resistant prostate cancer (mCRPC). We performed 16S rRNA gene sequencing of fecal DNA from 23 individuals with mCRPC progressing on enzalutamide and just prior to treatment with anti-PD-1 (pembrolizumab) to determine whether certain features of the microbiome are associated with treatment response (defined as serum PSA decrease >50% at any time on treatment or radiographic response per RECIST V.1.1). Global bacterial composition was similar between responders and non-responders, as assessed by multiple alpha and beta diversity metrics. However, certain bacterial taxa identified by sequencing across multiple 16S rRNA hypervariable regions were consistently associated with response, including the archetypal oral bacterium Streptococcus salivarius. Quantitative PCR (qPCR) of DNA extracts from fecal samples confirmed increased Streptococcus salivarius fecal levels in responders, whereas qPCR of oral swish DNA extracts showed no relationship between oral Streptococcus salivarius levels and response status. Contrary to previous reports in other cancer types, Akkermansia muciniphila levels were reduced in responder samples as assessed by both 16S rRNA sequencing and qPCR. We further analyzed our data in the context of a previously published “integrated index” describing bacteria associated with response and non-response to checkpoint inhibition. We found that the index was not reflective of response status in our cohort. Lastly, we demonstrate little change in the microbiome over time, and with pembrolizumab treatment. Our results suggest that the association between fecal microbiota and treatment response to immunotherapy may be unique to cancer type and/or previous treatment history.
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