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Ebola virus disease (EVD) is a potentially fatal infectious disease, easily transmitted through direct contact with infected body fluids. Children exhibit a range of nonspecific clinical signs that mirror common [...]

Ebola virus disease (EVD) has ranked among the deadliest of all infectious diseases since its documented emergence during 1976 in Zaire (now the Democratic Republic of the Congo; DRC) (2). [...]

Background Although multiple prognostic models exist for Ebola virus disease mortality, few incorporate biomarkers, and none has used longitudinal point-of-care serum testing throughout Ebola treatment center care. Methods This retrospective study evaluated adult patients with Ebola virus disease during the 10th outbreak in the Democratic Republic of Congo. Ebola virus cycle threshold (Ct; based on reverse transcriptase polymerase chain reaction) and point-of-care serum biomarker values were collected throughout Ebola treatment center care. Four iterative machine learning models were created for prognosis of mortality. The base model used age and admission Ct as predictors. Ct and biomarkers from treatment days 1 and 2, days 3 and 4, and days 5 and 6 associated with mortality were iteratively added to the model to yield mortality risk estimates. Receiver operating characteristic curves for each iteration provided period-specific areas under curve with 95% CIs. Results Of 310 cases positive for Ebola virus disease, mortality occurred in 46.5%. Biomarkers predictive of mortality were elevated creatinine kinase, aspartate aminotransferase, blood urea nitrogen (BUN), alanine aminotransferase, and potassium; low albumin during days 1 and 2; elevated C-reactive protein, BUN, and potassium during days 3 and 4; and elevated C-reactive protein and BUN during days 5 and 6. The area under curve substantially improved with each iteration: base model, 0.74 (95% CI,.69–.80); days 1 and 2, 0.84 (95% CI,.73–.94); days 3 and 4, 0.94 (95% CI,.88–1.0); and days 5 and 6, 0.96 (95% CI,.90–1.0). Conclusions This is the first study to utilize iterative point-of-care biomarkers to derive dynamic prognostic mortality models. This novel approach demonstrates that utilizing biomarkers drastically improved prognostication up to 6 days into patient care. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate maternal, fetal, and perinatal outcomes during the 2018–2020 Ebola outbreak in Democratic Republic of Congo (DRC). Methods: Mortality between pregnant and non-pregnant women of reproductive age admitted to DRC's Mangina Ebola treatment center (ETC) were compared using propensity score matching. Propensity scores were calculated using age, initial Ebola viral load, Ebola vaccination status, and investigational therapeutic. Additionally, fetal and perinatal outcomes of pregnancies were also described. Results: Twenty-seven pregnant women were admitted to the Mangina ETC during December 2018—January 2020 among 162 women of childbearing age. We found no evidence of increase mortality among pregnant women compared to non-pregnant women (relative risk:1.0, 95%CI: 0.58–1.72). Among surviving mothers, pregnancy outcomes were poor with at least 58% (11/19) experiencing loss of pregnancy while 16% (3/19) were discharged with viable pregnancy. Two mothers with viable pregnancies were vaccinated, and all received investigational therapeutics. Two live births occurred, with one infant surviving after the infant and mother received an investigational post-exposure prophylaxis and Ebola therapeutic respectively. Conclusions: Pregnancy was not associated with increased mortality among women with EVD in the Mangina ETC. Fetal and perinatal outcomes remained poor in pregnancies complicated by EVD, though novel therapeutics may have potential for improving these outcomes. [ABSTRACT FROM AUTHOR]

Populations affected by humanitarian crises and emerging infectious disease outbreaks may have unique concerns and experiences that influence their perceptions toward vaccines. In March 2021, we conducted a survey to examine the perceptions toward COVID-19 vaccines and identify the factors associated with vaccine intention among 631 community members (CMs) and 438 healthcare workers (HCWs) affected by the 2018–2020 Ebola Virus Disease outbreak in North Kivu, Democratic Republic of the Congo. A multivariable logistic regression was used to identify correlates of vaccine intention. Most HCWs (81.7%) and 53.6% of CMs felt at risk of contracting COVID-19; however, vaccine intention was low (27.6% CMs; 39.7% HCWs). In both groups, the perceived risk of contracting COVID-19, general vaccine confidence, and male sex were associated with the intention to get vaccinated, with security concerns preventing vaccine access being negatively associated. Among CMs, getting the Ebola vaccine was associated with the intention to get vaccinated (RR 1.43, 95% CI 1.05–1.94). Among HCWs, concerns about new vaccines' safety and side effects (OR 0.72, 95% CI 0.57–0.91), religion's influence on health decisions (OR 0.45, 95% CI 0.34–0.61), security concerns (OR 0.52, 95% CI 0.37–0.74), and governmental distrust (OR 0.50, 95% CI 0.35–0.70) were negatively associated with vaccine perceptions. Enhanced community engagement and communication that address this population's concerns could help improve vaccine perceptions and vaccination decisions. These findings could facilitate the success of vaccine campaigns in North Kivu and similar settings. [ABSTRACT FROM AUTHOR]

Background: Ebola Virus Disease (EVD) causes high case fatality rates (CFRs) in young children, yet there are limited data focusing on predicting mortality in pediatric patients. Here we present machine learning-derived prognostic models to predict clinical outcomes in children infected with Ebola virus. Methods: Using retrospective data from the Ebola Data Platform, we investigated children with EVD from the West African EVD outbreak in 2014–2016. Elastic net regularization was used to create a prognostic model for EVD mortality. In addition to external validation with data from the 2018–2020 EVD epidemic in the Democratic Republic of the Congo (DRC), we updated the model using selected serum biomarkers. Findings: Pediatric EVD mortality was significantly associated with younger age, lower PCR cycle threshold (Ct) values, unexplained bleeding, respiratory distress, bone/muscle pain, anorexia, dysphagia, and diarrhea. These variables were combined to develop the newly described EVD Prognosis in Children (EPiC) predictive model. The area under the receiver operating characteristic curve (AUC) for EPiC was 0.77 (95% CI: 0.74–0.81) in the West Africa derivation dataset and 0.76 (95% CI: 0.64–0.88) in the DRC validation dataset. Updating the model with peak aspartate aminotransferase (AST) or creatinine kinase (CK) measured within the first 48 hours after admission increased the AUC to 0.90 (0.77–1.00) and 0.87 (0.74–1.00), respectively. Conclusion: The novel EPiC prognostic model that incorporates clinical information and commonly used biochemical tests, such as AST and CK, can be used to predict mortality in children with EVD. Author summary: Although case fatality rates remain high, there are limited data on predicting mortality in children with Ebola Virus Disease (EVD). Furthermore, challenges in predicting EVD outcomes using clinical and laboratory data highlight the need for the development and validation of pediatric predictive models. The novel EVD Prognosis in Children (EPiC) model uses clinical and biochemical information, such as AST and CK, to predict mortality in infected children. While few prognostic models or scoring systems have been developed to predict clinical outcomes of EVD, the majority of them were limited in geographical and temporal scope having been derived using data from one location. As such, the EPiC model is the first externally validated model for the prognosis of pediatric EVD using diverse datasets from geographically and temporally separate outbreaks. This model can be easily applied by bedside clinicians to assess pediatric patients at risk for death and help to allocate resources accordingly. [ABSTRACT FROM AUTHOR]

Vaccine hesitancy among displaced populations is associated with inequitable access to services and mistrust of authorities, among other factors. This study evaluated variations in attitudes toward COVID-19 vaccines and factors associated with vaccine acceptance among refugees and Lebanese nationals accessing 60 International Medical Corps-supported health facilities through two cross-sectional surveys pre- (n = 3927; Survey 1) and post- (n = 4174; Survey 2) vaccine rollout. Logistic regression was used to assess predictors of vaccine acceptance using the health beliefs model. Refugees comprised 52.9% (Survey 1) and 54.2% (Survey 2) of respondents. Vaccine acceptance was low among both groups in Survey 1 (25.9% refugees vs. 23.1% Lebanese nationals), but higher in Survey 2 in Lebanese (57.6%) versus refugees (32.9%). Participants reported greater perceived benefits of vaccination, higher perceived COVID-19 susceptibility, and lower perceived vaccination barriers in Survey 2 versus Survey 1. Post-vaccine rollout, refugees had lower odds of vaccine acceptance compared to Lebanese (OR 0.50, 95%CI 0.41–0.60), while older age (OR 1.37, 95%CI 1.06–1.78, ≥51 years vs. 18–30 years) was associated with greater vaccine acceptance. Health beliefs model variables were associated with vaccine acceptance in both surveys. Tailored strategies to respond dynamically to changes in vaccine attitudes among vulnerable groups in Lebanon are essential for equitable vaccine uptake. [ABSTRACT FROM AUTHOR]

Conflict and mass displacement into Protection of Civilian (POCs) sites in South Sudan led to the breakdown of community and family structures, increasing women and girls' vulnerability to gender-based violence and exacerbating already poor sexual and reproductive health outcomes. As one component of a study on post-abortion care, this study explores community perceptions of unintended pregnancy and abortion in a POC in Juba. Four focus group discussions were conducted with 36 women and married men aged 18–45 living in the POC. Although initial reactions to induced abortion were generally negative, participants discussed that unintended pregnancy and induced abortion appeared to have increased during the current conflict. Their discussion of abortion became less condemnatory as they described changes in people's situation due to war, including instability and poverty, transactional sex, disruption of marital norms, rape, and low contraceptive use. This is one of the first studies to investigate community perceptions and practices related to unintended pregnancy and abortion in South Sudan. Despite the beliefs that these are taboo topics, the discussions provide an opening to reduce abortion stigma. To ensure lasting stigma reduction, investment in women and girls to improve gender equity is needed. [ABSTRACT FROM AUTHOR]

Background: In the aftermath of the devastating 2015 earthquakes in Nepal, three non-governmental organizations collaborated to develop a program responding to the immediate mental health and psychosocial support (MHPSS) needs in three severely affected districts: Dhading, Gorkha, and Sindhuli. The program was implemented between April 2015 and February 2017 and aimed to (i) strengthen health worker capacity to provide integrated MHPSS services; and (ii) increase access to mental health services. This paper describes the program's implementation and the results of a pragmatic evaluation of the program's overall reach, effectiveness, and lessons learned. Methods: The mixed-methods evaluation used routine program data, quantitative data from pre- and post-tests conducted with trainees and service users, and qualitative data from stakeholder interviews and focus group discussions. Results: A total of 1041 health workers received MHPSS training and supervision. Participants demonstrated significant improvements in skills, knowledge, and self-rated perceived competency. Trainees went on to provide MHPSS services to 3422 people. The most commonly identified presenting problems were epilepsy (29%) and depression (26%). A total of 67% of service users reported being 'completely satisfied' with the services received and 83% of those experiencing severe functional impairments on enrollment demonstrated improvement after receiving services. Conclusions: Despite operational challenges, the program successfully engaged both laypeople and health workers to provide MHPSS in the aftermath of the crisis. Lessons learned can inform the planning and implementation of future training and integration programs to provide large-scale MHPSS efforts in humanitarian settings. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between oral third-generation cephalosporin antibiotic treatment and mortality in Ebola virus disease (EVD).Methods: This retrospective cohort studied EVD-infected patients admitted to five Ebola Treatment Units in Sierra Leone and Liberia during 2014-15. Empiric treatment with cefixime 400 mg once daily for five days was the clinical protocol; however, due to resource variability, only a subset of patients received treatment. Data on sociodemographics, clinical characteristics, malaria status and Ebola viral loads were collected. The primary outcome was mortality compared between cases treated with cefixime within 48 h of admission to those not treated within 48 h. Propensity scores were derived using clinical covariates. Mortality between treated and untreated cases was compared using propensity-matched conditional logistic regression and bootstrapped log-linear regression analyses to calculate an odds ratio (OR) and relative risk (RR), respectively, with associated 95% confidence intervals (CI).Results: Of 424 cases analysed, 360 (84.9%) met the cefixime treatment definition. The mean age was 30.5 years and 40.3% were male. Median cefixime treatment duration was 4 days (IQR: 3, 5). Among cefixime-treated patients, mortality was 54.7% (95% CI: 49.6-59.8%) vs. 73.4% (95% CI: 61.5-82.7%) in untreated patients. In conditional logistic regression, mortality likelihood was significantly lower among cases receiving cefixime (OR = 0.48, 95% CI: 0.32-0.71; P = 0.01). In the bootstrap analysis, a non-significant risk reduction was found with cefixime treatment (RR = 0.82, 95% CI: 0.64-1.16, P = 0.11).Conclusion: Early oral cefixime may be associated with reduced mortality in EVD and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background Intravenous fluid (IVF) is a frequently recommended intervention in Ebola virus disease (EVD), yet its impact on patient outcomes remains unclear. Methods This retrospective cohort study evaluated patients with EVD admitted to 5 Ebola treatment units (ETUs) in West Africa. The primary outcome was the difference in 28-day survival between cases treated and not treated with IVF. To control for demographic and clinical factors related to both IVF exposure and survival, cases were compared using propensity score matching. To control for time-varying patient and treatment factors over the course of ETU care, a marginal structural proportional hazards model (MSPHM) with inverse probability weighting was used to assess for 28-day survival differences. Results Among 424 EVD-positive cases with data for analysis, 354 (83.5%) were treated with IVF at some point during their ETU admission. Overall, 146 (41.3%) cases treated with IVF survived, whereas 31 (44.9%) cases not treated with any IVF survived (P =.583). Matched propensity score analysis found no significant difference in 28-day survival between cases treated and not treated with IVF during their first 24 and 48 hours of care. Adjusted MSPHM survival analyses also found no significant difference in 28-day survival for cases treated with IVF (27.3%) compared to those not treated with IVF (26.9%) during their entire ETU admission (P =.893). Conclusions After adjustment for patient- and treatment-specific time-varying factors, there was no significant difference in survival among patients with EVD treated with IVF as compared to those not treated with IVF. [ABSTRACT FROM AUTHOR]

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Mitochondrial research has influenced concepts in anthropology, human physiology and pathophysiology. We present here direct evidence that human recombinant viruses can localize in mitochondria to disrupt their integrity. This finding, while opening new perspectives in viral gene therapy, may provide new insights into the pathogenesis, prevention and treatment of viral diseases. In addition, it may advance the current understanding of cell evolution. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Experiments in vitro have shown that the drug amodiaquine may inhibit Ebola virus activity. During the Ebola virus disease (EVD) epidemic in West Africa in 2014–2016, 2 mass drug administrations (MDAs) of artesunate-amodiaquine (ASAQ) were implemented to decrease the burden of malaria. The objective of this study was to assess the effect of the ASAQ MDAs on the mortality of patients with EVD. Methods A retrospective cohort design was used to analyze mortality data for patients with EVD admitted to 5 Ebola treatment units in Liberia and Sierra Leone. Patients admitted to the ETUs during the time period of ASAQ's therapeutic effect from areas where the MDA was implemented were matched to controls not exposed to ASAQ, using a range of covariates, including malaria co-infection status, and a logistic regression analysis was performed. The primary outcome was Ebola treatment unit mortality. Results A total of 424 patients with EVD had sufficient data for analysis. Overall, the mortality of EVD patients was 57.5%. A total of 22 EVD patients were exposed to ASAQ during the MDAs and were found to have decreased risk of death compared with those not exposed in a matched analysis, but this did not reach statistical significance (relative risk, 0.63; 95% confidence interval, 0.37–1.07; P =.086). Conclusions There was a non–statistically significantly decreased risk of mortality in EVD patients exposed to ASAQ during the 2 MDAs as compared with EVD patients not exposed to ASAQ. Further prospective trials are needed to determine the direct effect of ASAQ on EVD mortality. [ABSTRACT FROM AUTHOR]

The tenth Ebola Virus Disease (EVD) outbreak (2018-2020, North Kivu, Ituri, South Kivu) in the Democratic Republic of the Congo (DRC) was the second-largest EVD outbreak in history. During this outbreak, Ebola vaccination was an integral part of the EVD response. We evaluated community perceptions toward Ebola vaccination and identified correlates of Ebola vaccine uptake among high-risk community members in North Kivu, DRC. In March 2021, a cross-sectional survey among adults was implemented in three health zones. We employed a sampling approach mimicking ring vaccination, targeting EVD survivors, their household members, and their neighbors. Outbreak experiences and perceptions toward the Ebola vaccine were assessed, and modified Poisson regression was used to identify correlates of Ebola vaccine uptake among those offered vaccination. Among the 631 individuals surveyed, most (90.2%) reported a high perceived risk of EVD and 71.6% believed that the vaccine could reduce EVD severity; however, 63.7% believed the vaccine had serious side effects. Among the 474 individuals who had been offered vaccination, 397 (83.8%) received the vaccine, 180 (45.3%) of those vaccinated received the vaccine after two or more offers. Correlates positively associated with vaccine uptake included having heard positive information about the vaccine (RR 1.30, 95% CI 1.06-1.60), the belief that the vaccine could prevent EVD (RR 1.23, 95% CI 1.09-1.39), and reporting that religion influenced all decisions (RR 1.13, 95% CI 1.02-1.25). Ebola vaccine uptake was high in this population, although mixed attitudes and vaccine delays were common. Communicating positive vaccine information, emphasizing the efficacy of the Ebola vaccine, and engaging religious leaders to promote vaccination may aid in increasing Ebola vaccine uptake during future outbreaks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Countries affected by armed conflict have higher maternal mortality than stable settings. South Sudan has one of the highest maternal mortality ratios in the world, with an estimated 789 maternal deaths per 100,000 live births. Long-term socio-political instability has contributed to significant challenges in its health system. To reduce maternal and newborn morbidity and mortality, South Sudan must increase the number of skilled midwives., Methods: A cross-sectional mixed methods study was conducted in 2022 to assess the midwifery education program at three schools receiving support from International Medical Corps in South Sudan, including in-depth interviews with 15 midwifery school graduates currently working as midwives, their supervisors, 16 school faculty (in dyads), and two Ministry of Health officials; and nine focus group discussions with women clients of graduate midwives., Results: Participants identified strengths of the schools, including being well equipped with trained and competent teaching staff, competency-based curriculum, including practical training which prepared graduate midwives to apply their skills in practice. Weaknesses of the program included its dependence on donor funding, inadequate mentorship and number of tutors, and insufficient practice for some services due to low client load at clinical sites. Additionally, participants identified challenges affecting midwives' ability to provide good quality care, including lack of equipment and supplies, low client load, low salaries, and insecurity due to conflict. Nevertheless, women in the community appreciated the immense work that midwives do. Midwives were respected by the community at large, and graduates expressed pride and satisfaction in their job, as well as the positive impact they have had in providing critical services to communities., Discussion: Overall, the quality of the midwifery education program appears to be strong, however gaps in the program and the provision of quality care remain. The findings highlight the need to ensure sustained funding for midwifery education, as well as health system strengthening to ensure midwives can practice their skills. Continued investment in midwifery education and training is critical to reduce high maternal mortality and morbidity in South Sudan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Perera, Isa, Sebushishe, Sundararaj, Piccirillo, Xia, Langaigne, Ali and Casey.)

Introduction: During the 2018-2020 Ebola virus disease (EVD) outbreak in the eastern part of the Democratic Republic of the Congo (DRC), prevention and control measures, such as Ebola vaccination were challenging by community mistrust. We aimed to understand perceptions regarding Ebola vaccination and identify determinants of Ebola vaccine uptake among HCWs., Methods: In March 2021, we conducted a cross-sectional survey among 438 HCWs from 100 randomly selected health facilities in three health zones (Butembo, Beni, Mabalako) affected by the 10th EVD outbreak in North Kivu, DRC. HCWs were eligible if they were ≥ 18 years and were working in a health facility during the outbreak. We used survey logistic regression to assess correlates of first-offer uptake (i.e., having received the vaccine the first time it was offered vs. after subsequent offers)., Results: Of the 438 HCWs enrolled in the study, 420 (95.8%) reported that they were eligible and offered an Ebola vaccine. Among those offered vaccination, self-reported uptake of the Ebola vaccine was 99.0% (95% confidence interval (CI) [98.5-99.4]), but first-offer uptake was 70.2% (95% CI [67.1, 73.5]). Nearly all HCWs (94.3%; 95% CI [92.7-95.5]) perceived themselves to be at risk of contracting EVD. The most common concern was that the vaccine would cause side effects (65.7%; 95% CI [61.4-69.7]). In the multivariable analysis, mistrust of the vaccine source or how the vaccine was produced decreased the odds of first-time uptake., Discussion: Overall uptake of the Ebola vaccine was high among HCWs, but uptake at the first offer was substantially lower, which was associated with mistrust of the vaccine source. Future Ebola vaccination efforts should plan to make repeated vaccination offers to HCWs and address their underlying mistrust in the vaccines, which can, in turn, improve community uptake., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Doshi, Garbern, Kulkarni, Perera, Fleming, Muhayangabo, Ombeni, Tchoualeu, Kallay, Song, Powell, Gainey, Glenn, Mutumwa, Hans Bateyi Mustafa, Earle-Richardson, Gao, Abad, Soke, Fitter, Hyde, Prybylski, Levine, Jalloh and Mbong.)

Background: In the aftermath of the devastating 2015 earthquakes in Nepal, three non-governmental organizations collaborated to develop a program responding to the immediate mental health and psychosocial support (MHPSS) needs in three severely affected districts: Dhading, Gorkha, and Sindhuli. The program was implemented between April 2015 and February 2017 and aimed to (i) strengthen health worker capacity to provide integrated MHPSS services; and (ii) increase access to mental health services. This paper describes the program's implementation and the results of a pragmatic evaluation of the program's overall reach, effectiveness, and lessons learned., Methods: The mixed-methods evaluation used routine program data, quantitative data from pre- and post-tests conducted with trainees and service users, and qualitative data from stakeholder interviews and focus group discussions., Results: A total of 1041 health workers received MHPSS training and supervision. Participants demonstrated significant improvements in skills, knowledge, and self-rated perceived competency. Trainees went on to provide MHPSS services to 3422 people. The most commonly identified presenting problems were epilepsy (29%) and depression (26%). A total of 67% of service users reported being 'completely satisfied' with the services received and 83% of those experiencing severe functional impairments on enrollment demonstrated improvement after receiving services., Conclusions: Despite operational challenges, the program successfully engaged both laypeople and health workers to provide MHPSS in the aftermath of the crisis. Lessons learned can inform the planning and implementation of future training and integration programs to provide large-scale MHPSS efforts in humanitarian settings., Competing Interests: None., (© The Author(s) 2021.)

[¹³¹I]meta-iodobenzylguanidine ([¹³¹I]MIBG) is the most commonly used treatment for metastatic pheochromocytoma and paraganglioma. It enters the chromaffin cells via the membrane norepinephrine transporter; however, its success has been modest. We studied the ability of histone deacetylase (HDAC) inhibitors to enhance [¹²³I]MIBG uptake by tumors in a mouse metastatic pheochromocytoma model. HDAC inhibitors are known to arrest growth, induce differentiation and apoptosis in various cancer cells, and further inhibit tumor growth. We report the in vitro and in vivo effects of two HDAC inhibitors, romidepsin and trichostatin A, on the uptake of [(3)H]norepinephrine, [¹²³I]MIBG, and [(18)F]fluorodopamine in a mouse model of metastatic pheochromocytoma. The effects of both inhibitors on norepinephrine transporter activity were assessed in mouse pheochromocytoma (MPC) cells by using the transporter-blocking agent desipramine and the vesicular-blocking agent reserpine. HDAC inhibitors increased [(3)H]norepinephrine, [¹²³I]MIBG, and [(18)F]fluorodopamine uptake through the norepinephrine transporter in MPC cells. In vivo, inhibitor treatment resulted in significantly increased uptake of [(18)F]fluorodopamine positron emission tomography (PET) in pheochromocytoma liver metastases (19.1 ± 3.2% injected dose per gram of tumor (%ID/g) compared to liver metastases in pretreatment scans 5.9 ± 0.6%; P<0.001). Biodistribution analysis after inhibitors treatment confirmed the PET results. The uptake of [(123)I]MIBG was significantly increased in liver metastases 9.5 ± 1.1% compared to 3.19 ± 0.4% in untreated control liver metastases (P<0.05). We found that HDAC inhibitors caused an increase in the amount of norepinephrine transporter expressed in tumors. HDAC inhibitors may enhance the therapeutic efficacy of [(131)I]MIBG treatment in patients with advanced malignant pheochromocytoma and paraganglioma.