bluuebunny/crossref_metadata_2025 huggingface dataset:
Personality and Hearing Acuity: Evidence From the Health and Retirement Study and the English Longitudinal Study of Ageing
Authors: Stephan Yannick , Sutin Angelina R. , Caille Pauline , Terracciano Antonio
Published: July 2019

Objective

Several determinants of age-related hearing impairment have been identified, but little is known about the predictive value of psychological factors. The present study examined whether five-factor model personality traits are prospectively associated with hearing acuity in middle-aged and older adults.

Methods

Participants were adults aged 50 to 97 years (N > 10,000) drawn from the Health and Retirement Study (2012–2016) and the English Longitudinal Study of Ageing (2010–2014). In each sample, personality, demographic factors, health-related behaviors, body mass index, and memory function were assessed at baseline, and objective hearing acuity was measured 4 years later.

Results

In both samples, higher conscientiousness and openness were associated with better hearing acuity and lower risk of impairment, whereas neuroticism was associated with a higher risk of hearing impairment. In the Health and Retirement Study and English Longitudinal Study of Ageing, respectively, 1 standard deviation (1-SD) higher conscientiousness, 1-SD higher openness, and 1-SD lower neuroticism were related to 13% to 10%, 8% to 6%, and 10% to 13% lower likelihoods of hearing impairment, respectively. In both samples, additional analyses revealed that physical activity and memory mediated the association between personality and hearing.

Conclusions

The present study provides robust evidence for an association between personality traits and hearing function. The findings broaden knowledge on risk and mitigating factors for age-related hearing impairment, which has implications for the quality of life of middle-aged and older adults.
Brief Report: No Evidence for an Association Between Statin Use and Lower Biomarkers of HIV Persistence or Immune Activation/Inflammation During Effective ART
Authors: Bedimo Roger J. , Mar Hanna , Bosch Ronald J. , Drechsler Henning , Cyktor Joshua C. , Macatangay Barnard J. C. , Lalama Christina , Rinaldo Charles , Collier Ann , Godfrey Catherine , Hogg Evelyn , Hensel Christopher , Eron Joseph J. , Mcmahon Deborah K. , Mellors John W. , Tebas Pablo , Gandhi Rajesh T. ,   A5321 Study Team
Published: July 2019

Background:

Statins exert pleiotropic anti-inflammatory and immune-modulatory effects, which might translate into antiviral activity. We evaluated whether reported current statin exposure is associated with lower levels of markers of HIV persistence and immune activation/inflammation.

Methods:

We compared levels of markers of HIV viral persistence [cell-associated HIV RNA (CA-RNA), CA-DNA, and single copy assay plasma HIV RNA] and immune activation/inflammation (IL-6, IP-10, neopterin, sCD14, sCD163, and TNF-alpha) between statin users and nonusers among participants of ACTG A5321 who initiated antiretroviral therapy (ART) during chronic infection and maintained virologic suppression (HIV-1 RNA levels ≤50 copies/mL) for ≥3 years.

Results:

A total of 303 participants were analyzed. Median time on the current statin was 2.9 years (1.2–5.1). There were no differences between statin users and nonusers in levels of CA-DNA (median 650 vs. 540 copies/106 CD4+ T cells; P = 0.58), CA-RNA (53 vs. 37 copies/106 CD4+ T cells; P = 0.12), or single copy assay (0.4 vs. 0.4 copies/mL; P = 0.45). Similarly, there were no significant differences between statin users and nonusers in markers of inflammation/activation, except for IP-10 (137 vs. 118 pg/mL; P = 0.028). Findings were unchanged after adjustment for factors including pre-ART CD4 and HIV RNA, and years on ART.

Conclusions:

In this cohort of persons on long-term suppressive ART, current statin use was not associated with lower levels of HIV persistence or immune activation/inflammation. These results do not support a major role for statins in reducing HIV persistence, although an early transient effect cannot be excluded. Prospective, randomized studies are needed to confirm these findings.
Transition Pathways Out of Pediatric Care and Associated HIV Outcomes for Adolescents Living With HIV in South Africa
Authors: Haghighat Roxanna , Toska Elona , Cluver Lucie , Gulaid Laurie , Mark Daniella , Bains Anurita
Published: July 2019

Background:

Research on adolescent transitions out of pediatric HIV care has focused on high-income countries, with limited understanding of transitions in sub-Saharan Africa's public health sector.

Methods:

Patient file data were extracted through December 2017 for all 10- to 19-year olds ever initiated on antiretroviral therapy in a health district of the Eastern Cape, South Africa (n = 951). Pathways in HIV care were identified by tracing movements across facility care types and levels. Associations between pathways and viral failure, mortality, loss to follow-up, and viral load change were tested in sequential multivariable regressions. Analyses controlled for sociodemographic and treatment-related variables. Thematic analyses of semistructured health care provider interviews identified transition support at included facilities.

Results:

Only 57.8% of adolescents had initiated antiretroviral therapy in pediatric care, and 20.4% of the total cohort had transitioned out of pediatric HIV care. Among the 42.2% who had initiated in nonpediatric care, 93.8% remained exclusively in nonpediatric care. Median age at first transition was 14 years. Two main pathways were identified: classical transition to adult HIV care (43.3%) and down referral transition to primary health care clinics (56.7%). Across pathways, 27.3% experienced cyclical transition or repeated movement between pediatric and nonpediatric care. Independent of covariates, adolescents with down referral transition were less likely to demonstrate viral failure (adjusted odds ratio, 0.21; 95% confidence interval: 0.10 to 0.42; P < 0.001). Mortality and loss to follow-up were not associated with either pathway. Median posttransition viral load change was not clinically significant (median, 0.00; interquartile range: 0.00–0.35) or associated with transition pathways. Health care providers described informal “protocols” for mitigating risk of negative posttransition HIV outcomes.

Conclusions:

This study proposes a contextually relevant model for transitions out of pediatric HIV care in South Africa. Feasible, scalable “protocols” may mitigate risk of worsening posttransition HIV outcomes.
Clinical and Virological Outcomes of TB/HIV Coinfected Patients Treated With Dolutegravir-Based HIV Antiretroviral Regimens: Programmatic Experience From Botswana
Authors: Modongo Chawangwa , Wang Qiao , Dima Mbatshi , Matsiri Ogopotse , Kgwaadira Botshelo , Rankgoane-Pono Goabaone , Shin Sanghyuk S. , Zetola Nicola M.
Published: July 2019

Background:

Dolutegravir (DTG) has recently been recommended as a preferred first-line regimen for the treatment of new and treatment-experienced HIV-infected patients. However, potential drug interactions between DTG and rifampicin remain a clinical and public health concern.

Methods:

We analyzed HIV and Tuberculosis (TB) treatment outcomes of HIV-infected patients concomitantly receiving rifampicin- and DTG-based regimens under programmatic conditions in Botswana. The outcomes of interest were successful TB treatment and viral load suppression. We used multivariable logistic models to determine predictors for each outcome of interest.

Results:

A total of 1225 patients were included in the analysis to evaluate predictors of successful TB outcome. Among patients on DTG and non-DTG regimens, 90.9% and 88.3% achieved favorable TB treatment outcomes, respectively. Of those who received DTG-based regimen; 44% received once-daily dosing and 53% twice-daily dosing. We found that DTG was associated with favorable TB treatment outcome (adjusted odds ratio = 1.56; 95% confidence interval = 1.06 to 2.31), after adjusting for age, gender, and CD4 cell counts. High rates of viral load suppression were found across all antiretroviral therapy (ART) regimen categories (>92% for all). We did not find an independent association between DTG and viral suppression after adjustment of other covariates.

Conclusions:

The use of DTG-based ART regimens in patients coinfected with TB and HIV lead to favorable TB and HIV treatment outcomes, comparable to those achieved with alternative ART regimens. Our results provide reassurance to TB and HIV programs about the overall programmatic concomitant use of these first-line treatment regimens for the management of HIV and TB coinfected patients.
Short- and Long-Term Pharmacologic Measures of HIV Pre-exposure Prophylaxis Use Among High-Risk Men Who Have Sex With Men in HPTN 067/ADAPT
Authors: Velloza Jennifer , Bacchetti Peter , Hendrix Craig W. , Murnane Pamela , Hughes James P. , Li Maoji , Curlin Marcel E. , Holtz Timothy H. , Mannheimer Sharon , Marzinke Mark A. , Amico K. Rivet , Liu Albert , Piwowar-Manning Estelle , Eshleman Susan H. , Dye Bonnie J. , Gandhi Monica , Grant Robert M. ,   HPTN 067/ADAPT Study Team
Published: July 2019

Background:

The effectiveness of oral emtricitabine (FTC)/tenofovir (TFV) disoproxil fumarate–based HIV pre-exposure prophylaxis (PrEP) depends on adherence. Pharmacologic measures help interpret patterns and predictors of PrEP adherence.

Setting:

We analyzed data from the subsample of men who have sex with men enrolled in HPTN 067/ADAPT in Bangkok, Thailand, and Harlem, NY, U.S.

Methods:

After a 5-week directly observed therapy period, participants were randomized to daily, time-driven, or event-driven PrEP. Follow-up occurred at weeks 4, 12, and 24 after randomization. Plasma and hair FTC/TFV levels indicated short- and long-term PrEP use, respectively. Electronic pill bottle data (Wisepill) were collected weekly. Pearson correlation coefficients between PrEP use measures were calculated; linear mixed models assessed predictors of plasma and hair drug concentrations.

Results:

Among 350 participants (median age: 31 years, interquartile range: 25–38), 49.7% were from Harlem, half had less than college education, and 21% reported heavy alcohol use. In multivariable models, being enrolled in Harlem, being in non–daily arms, and having less than college education were associated with lower hair FTC/TFV concentrations; heavy alcohol use was associated with higher concentrations. Similar results were found for plasma concentrations by site and arm, but older age and greater number of sex partners were associated with higher concentrations. Hair and plasma FTC/TFV concentrations were moderately correlated with Wisepill data (r ≥ 0.29) across visits.

Conclusions:

In HPTN067, plasma, hair, and Wisepill data correlated with one another and served as complementary adherence measures. Site, arm, education, age, alcohol, and sexual behavior influenced patterns of adherence.
Polypharmacy, Hazardous Alcohol and Illicit Substance Use, and Serious Falls Among PLWH and Uninfected Comparators
Authors: Womack Julie A. , Murphy Terrence E. , Rentsch Christopher T. , Tate Janet P. , Bathulapalli Harini , Smith Alexandria C. , Bates Jonathan , Jarad Samah , Gibert Cynthia L. , Rodriguez-Barradas Maria C. , Tien Phyllis C. , Yin Michael T. , Gill Thomas M. , Friedlaender Gary , Brandt Cynthia A. , Justice Amy C.
Published: July 2019

Background:

Medication classes, polypharmacy, and hazardous alcohol and illicit substance abuse may exhibit stronger associations with serious falls among persons living with HIV (PLWH) than with uninfected comparators. We investigated whether these associations differed by HIV status.

Setting:

Veterans Aging Cohort Study.

Methods:

We used a nested case–control design. Cases (N = 13,530) were those who fell. Falls were identified by external cause of injury codes and a machine-learning algorithm applied to radiology reports. Cases were matched to controls (N = 67,060) by age, race, sex, HIV status, duration of observation, and baseline date. Risk factors included medication classes, count of unique non–antiretroviral therapy (non-ART) medications, and hazardous alcohol and illicit substance use. We used unconditional logistic regression to evaluate associations.

Results:

Among PLWH, benzodiazepines [odds ratio (OR) 1.24; 95% confidence interval (CI) 1.08 to 1.40] and muscle relaxants (OR 1.29; 95% CI: 1.08 to 1.46) were associated with serious falls but not among uninfected (P > 0.05). In both groups, key risk factors included non-ART medications (per 5 medications) (OR 1.20, 95% CI: 1.17 to 1.23), illicit substance use/abuse (OR 1.44; 95% CI: 1.34 to 1.55), hazardous alcohol use (OR 1.30; 95% CI: 1.23 to 1.37), and an opioid prescription (OR 1.35; 95% CI: 1.29 to 1.41).

Conclusion:

Benzodiazepines and muscle relaxants were associated with serious falls among PLWH. Non-ART medication count, hazardous alcohol and illicit substance use, and opioid prescriptions were associated with serious falls in both groups. Prevention of serious falls should focus on reducing specific classes and absolute number of medications and both alcohol and illicit substance use.
Increased Risk of Executive Function and Emotional Behavioral Problems Among Virologically Well-Controlled Perinatally HIV-Infected Adolescents in Thailand and Cambodia
Authors: Kerr Stephen J. , Puthanakit Thanyawee , Malee Kathleen M. , Thongpibul Kulvadee , Ly Penh Sun , Sophonphan Jiratchaya , Suwanlerk Tulathip , Kosalaraksa Pope , Ounchanum Pradthana , Aurpibul Linda , Kanjanavanit Suparat , Ngampiyaskul Chaiwat , Chettra Kea , Robbins Reuben , Paul Robert , Ananworanich Jintanat , Mellins Claude A. ,   on behalf of the PREDICT Resilience Study
Published: July 2019

Background:

Large numbers of perinatally HIV-infected (PHIV) children are aging into adolescence. We examined cognitive and behavioral outcomes in a longitudinal cohort of Asian youth.

Methods:

We followed up 231 PHIV, 125 perinatally HIV-exposed, uninfected (HEU), and 138 HIV-unexposed, uninfected (HUU) adolescents (aged 10 years and older), matched by age/sex, in Thailand and Cambodia for 3 years. Executive function was assessed with Children's Color Trails Tests 1 and 2 (CCTT-1 and -2), the design fluency test, and the verbal fluency test. Working memory (Freedom from Distractibility Index) and processing speed index were assessed using WISC-III. Visual memory was assessed by design memory and design recognition subtests of the Wide Range Assessment of Memory and Learning (WRAML-2) and behavioral problems using the Child Behavior Checklist (CBCL). Generalized estimating equations examined adjusted odds ratios of cognitive impairment (Z-scores ≥2 SD below age-adjusted means of the HUU group) and CBCL T-scores in the borderline-clinical range (T-Scores ≥60) in PHIV and HEU versus HUU youth, adjusting for ethnicity, household income, and caregiver characteristics.

Results:

The median age at enrollment was 13.8 years, with 58% women and 63% Thai participants. PHIV youth had >86% virological suppression and significantly higher impairment rates on CCTT-1 and -2 tests, design fluency test, verbal fluency tests, design memory, and CBCL internalizing and externalizing problems. Results were mostly similar between HEU and HUU groups, apart from higher impairment rates on CCTT-1 and internalizing problems in HEU.

Conclusion:

Asian adolescents with PHIV remain at risk of cognitive and mental health problems despite HIV treatment. Selective risks are observed among HEU youth.
Brief Report: Urine Emtricitabine and Tenofovir Concentrations Provide Markers of Recent Antiretroviral Drug Exposure Among HIV-Negative Men Who Have Sex With Men
Authors: Haaland Richard E. , Martin Amy , Livermont Tamee , Fountain Jeffrey , Dinh Chuong , Holder Angela , Lupo Lindsey D. , Hall LaShonda , Conway-Washington Christopher , Kelley Colleen F.
Published: July 2019

Background:

Urine provides a minimally invasive specimen that may allow for development of rapid tests to detect antiretroviral drugs and provide opportunities to improve individual adherence. This study sought to determine whether urine could provide a biomarker of adherence for currently approved pre-exposure prophylaxis and HIV treatment regimens.

Methods:

Urine and blood were collected from 34 HIV-negative men who have sex with men aged 18–49 years, enrolled in a clinical trial comparing 2 antiretroviral regimens. Specimens were collected 4 and 24 hours after a single oral dose of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) (n = 10) or tenofovir alafenamide (TAF)/FTC/cobicistat (COBI)/elvitegravir (EVG) (n = 8), or after 4 and 10 days of daily oral TDF/FTC (n = 9) or TAF/FTC/COBI/EVG (n = 7). Tenofovir (TFV), FTC, and EVG were measured by high-performance liquid chromatography-mass spectrometry.

Results:

Median urine FTC concentrations at 4 and 24 hours were similar between men receiving TDF/FTC (4 hours 147 µg/mL; 24 hours 10 µg/mL) and men receiving TAF/FTC/COBI/EVG (4 hours 333 µg/mL, P = 0.173; 24 hours 13 µg/mL, P = 0.681). Median urine TFV concentrations were lower among men receiving TAF/FTC/COBI/EVG (4 hours 1.2 µg/mL; 24 hours 0.8 µg/mL) compared with men receiving TDF/FTC (4 hours 17 µg/mL, P < 0.001; 24 hours 7 µg/mL, P = 0.001). Urine TFV concentrations remained reduced among men receiving TAF/FTC/COBI/EVG compared with men receiving TDF/FTC after daily dosing. EVG was not consistently measurable in urine.

Conclusions:

High urine FTC and TFV concentrations could provide an indication of adherence to daily oral dosing with TDF or TAF-based regimens used for treatment and prevention.
Brief Report: Relationship Between ABCC4 SNPs and Hepatitis B Virus Suppression During Tenofovir-Containing Antiretroviral Therapy in Patients With HIV/HBV Coinfection
Authors: Archampong Timothy , Ojewale Oluwayemisi , Bears Kristi , Chen Yiqing , Lartey Margaret , Sagoe Kwamena W. , Obo-Akwa Adjoa , Gong Yan , Langaee Taimour , Kwara Awewura
Published: July 2019

Background:

Incomplete hepatitis B virus (HBV) suppression during antiretroviral therapy (ART) in HIV and HBV coinfected patients is common, but underlying factors are not fully elucidated. We hypothesize that genetic factors that influence nucleoside analog pharmacokinetics will affect HBV treatment response.

Methods:

HIV/HBV coinfected patients on tenofovir disoproxil fumarate/lamivudine (TDF/3TC)-containing ART were enrolled. Selected ABCC4 single nucleotide polymorphisms (SNPs) with known effects on nucleoside pharmacokinetics were genotyped using TaqMan assays. Relationship between ABCC4 SNPs and unsuppressed HBV DNA (HBV DNA ≥20 IU/mL) were examined.

Results:

Of the 50 participants on TDF/3TC-containing ART for a median (range) of 1.5 (1–7.4) years, 20 (40%) had unsuppressed HBV DNA. Participants with unsuppressed compared with those with suppressed HBV DNA were more likely to have negative HBe antibody, lower body mass index, and lower CD4 count at enrollment. Carriers of ABCC4 rs11568695 (G3724A) variant allele were more likely than noncarriers to have unsuppressed HBV (61.1% vs. 29.0%, P = 0.038). Among 36 patients with suppressed HIV RNA (presumed good ART adherence), ABCC4 rs11568695 variant carriers were more likely than noncarriers to have unsuppressed HBV (58.8% vs. 20.0% P = 0.021). Logistic regression analysis that included genetic and nongenetic factors identified ABCC4 rs11568695 variant allele, body mass index, and male sex as predictors of unsuppressed HBV DNA.

Conclusions:

We identified a novel association between ABCC4 rs11568695 SNP and poor HBV treatment response. If confirmed in further studies, ABCC4 genotyping could be used to identify individuals who may need intensified HBV therapy.
Use of Recommended Preventive Health Care Services and Variations in HIV Care Among Women With HIV in the United States, 2013–2014: Opportunities for Expanded Partnerships in Support of Ending the HIV Epidemic
Authors: Short William R. , Sutton Madeline Y. , Luo Qingwei , Frazier Emma L.
Published: July 2019

Background:

Despite recommendations for preventive health services and routine HIV care for HIV-positive women, limited data are available regarding uptake of recommendations.

Methods:

We used data from the 2013–2014 data cycles of the Medical Monitoring Project. We calculated weighted estimates and used multivariable logistic regression with adjusted prevalence ratios and 95% confidence intervals to examine associations between preventive health screenings, routine HIV care [based on viral load (VL) and CD4 measures as proxies], and sociodemographic factors.

Results:

Of 2766 women, 47.7% were 50 years and older, 61.7% non-Hispanic black, 37.2% had >high school education, 63.3% had been living with HIV for ≥10 years, 68.4% were living ≤the federal poverty level, 67.3% had public health insurance, 93.8% were prescribed antiretroviral therapy, and 66.1% had sustained/durable suppression (12 months). For women aged 18 years and older, cervical cancer, breast cancer, and sexually transmitted infection screenings were documented for 44.3%, 27.6%, and 34.7%, respectively; 26% did not meet 6-month, and 37% did not meet 12-month, VL and CD4 test measure goals. In multivariable analyses, women with no VLs in the past 6 months were less likely to be durably suppressed, and women who did not have ≥3 CD4 or VL tests (past 12 months) were less likely to be living above the poverty level and more likely to have public insurance compared with private health insurance (P < 0.05).

Conclusion:

Receipt of recommended preventive care was suboptimal. Targeted interventions are warranted to help ensure access to comprehensive HIV care and prevention services for women.
Influence of histo blood group antigen expression on susceptibility to enteric viruses and vaccines
Authors: Ramani Sasirekha , Giri Sidhartha
Published: July 2019

Purpose of review

Gastroenteritis results in substantial morbidity and mortality worldwide, especially in young children in low-and-middle-income settings. Rotavirus and norovirus are the leading causes of viral gastroenteritis. Although introduction of rotavirus vaccines into childhood immunization programmes has reduced disease burden, vaccine effectiveness remains low in developing countries. Norovirus is replacing rotavirus as the most common cause of diarrhea hospitalization in settings where rotavirus vaccines are highly effective. Genetically determined host factors, such as expression of histo blood group antigens (HBGAs) are hypothesized to play key roles in susceptibility to infections and gastroenteritis caused by these virus, as well as influence vaccine take.

Recent findings

Epidemiology studies provide strong support for virus genotype-dependent effects of host HBGA expression, specifically secretor status on susceptibility to rotavirus and norovirus. Secretor-positive persons are significantly more susceptible to gastroenteritis caused by rotavirus P[8] genotype, and to infection with the GII.4 genotype of human norovirus. There is increasing data on the role of secretor status on rotavirus vaccine take but results are currently conflicting. For analyses involving young infants, maternal HBGA status is an important factor to be considered in future studies.

Genetically determined HBGA expression influences susceptibility to enteric viruses of public health importance.
Fractional-dose yellow fever vaccination: how much more can we do with less?
Authors: Visser Leonardus G.
Published: July 2019

Purpose of review

Climate change, deforestation, urbanization, and increased population mobility have made the risk of large outbreaks of yellow fever more likely than ever. Yellow fever vaccine production barely meets demands. In this review, we address the causes of the recent yellow fever outbreaks, why fractional dose yellow fever vaccination works, the role of virus neutralizing antibodies in the protection against yellow fever, and the need for revaccination.

Recent findings

Human activities have profoundly changed the epidemiology of yellow fever. The excess of infectious viral particles in routine yellow fever vaccine batches allows for off-label use of fractional dose yellow fever vaccination in response to emergency situations. Two studies have confirmed long-term protection after fractional dose yellow fever vaccination. The need for the presence of virus neutralizing antibodies (VNA) to protect an individual against yellow fever depends on the epidemiological setting. In case of sylvatic transmission, population immunity is irrelevant for individual protection, as mosquitoes are transmitting the virus from infected nonhuman primates to human.

With the growing connectivity through air travel, countries with high densities of nonimmune populations and of the urban mosquito vector, Aedes aegypti, should ensure that their citizens are properly vaccinated against yellow fever before traveling to a yellow fever endemic country. In the situation of sylvatic transmission, the presence of protective levels of VNA will determine the outcome and may require revaccination at some point in time.
Cutaneous leishmaniasis in the 21st century: from the laboratory to the bedside
Authors: Barkati Sapha , Ndao Momar , Libman Michael
Published: July 2019

Purpose of review

Despite modern advances in molecular diagnostic tools and a better understanding of its complex pathophysiology, cutaneous leishmaniasis, a neglected tropical disease, remains a major global health problem. Laboratory methods to inform prognosis and treatment are not widely available, the therapeutic options are limited and have significant adverse effects, and emergence of drug resistance is a further complication. New advances in the understanding of the role of Leishmania RNA virus (LRV) as a prognostic factor, speciation methods and antimicrobial resistance testing and their limitations will be discussed.

Recent findings

LRV, an intracytoplasmic endosymbiont found mostly in Leishmania spp. associated with more severe disease, appears to play a role in modulating the host immune response and has been associated with treatment failure in some Viannia subgenus species. Proper speciation is an important guide to management. However, recent findings have demonstrated significant heterogeneity of results related to differences in genotyping methods.

Recognition of the role of LRV in immune modulation and response to treatment along with more accessible tools for its detection to guide management at the bedside should allow a better individualized approach. Improving accessibility and standardization of speciation methods and antimicrobial susceptibility testing should be major goals to improve cutaneous leishmaniasis management in the 21st century.
Meningitis vaccines in children: what have we achieved and where next?
Authors: McAlpine Alastair , Sadarangani Manish
Published: July 2019

Purpose of review

This review highlights the recent impacts of vaccines against the major bacterial causes of meningitis in children, and the challenges for further prevention of bacterial meningitis, with a focus on Streptococcus pneumoniae, Neisseria meningitidis and group B Streptococcus.

Recent findings

Conjugate vaccines against S. pneumoniae and N. meningitidis have resulted in dramatic reductions in bacterial meningitis globally where they have been used. Recent licensure and use of capsular group B meningococcal protein vaccines have further reduced meningococcal meningitis in infants, young children and adolescents for countries with endemic disease and during outbreaks.

Existing vaccines to prevent bacterial meningitis in children should be utilized in countries with significant numbers of cases of pneumococcal and/or meningococcal meningitis. Vaccines, which are able to protect against more than 13 serotypes of S. pneumoniae are in clinical trials and should be able to further reduce pneumococcal meningitis cases. Cost effective meningococcal vaccines against non-A capsular groups are needed for low-resource countries. There remains an urgent need for a vaccine against group B Streptococcus, which is a major cause of neonatal meningitis globally and for which no vaccine currently exists.
Diagnosis and treatment of biofilm infections in children
Authors: Munro Alasdair P.S. , Highmore Callum J. , Webb Jeremy S. , Faust Saul N.
Published: July 2019

Purpose of review

Biofilm-associated infections cause difficulties in the management of childhood chronic infections and other diseases, due to the invasive nature of interventions which are often necessary for definitive management. Despite their importance, there are challenges in diagnosing biofilm infections and gaps in clinicians’ understanding regarding the significance of biofilms.

Recent findings

Many chronic infections associated with biofilms remain difficult or impossible to eradicate with conventional therapy. Surgical intervention, implant removal or long-term intermittent or suppressive antimicrobial therapy may be required. There are still significant challenges in detecting biofilms which presents a barrier in clinical practice and research. Novel therapies to disrupt biofilms are currently under investigation, which may help reduce the impact of antimicrobial resistance.

Biofilm-associated infection should be considered wherever there is clinical concern for an infection affecting prosthetic material, where there is a predisposing condition such as suppurative lung disease; or in the setting of chronic or relapsing infections which may be culture negative. New diagnostic methods for detecting biofilms are a research priority for both clinical diagnosis and the ability to conduct high quality clinical trials of novel antibiofilm interventions.
Paediatric sepsis
Authors: Schlapbach Luregn J.
Published: July 2019

Purpose of review

Sepsis remains among the leading causes of childhood mortality worldwide. This review serves to highlight key areas of knowledge gain and ongoing controversies pertinent to sepsis in children.

Recent findings

Several recent publications describe the epidemiology of paediatric sepsis, demonstrating the impact on child health in terms of mortality and morbidity, and the shortcomings of current paediatric sepsis definitions. Although emerging data support the importance of organ dysfunction as a hallmark of paediatric sepsis, the understanding of host susceptibility to sepsis and to sepsis severity remains very limited. Next-generation sequencing and host transcriptomics have the potential to provide new insights into the pathogenesis of sepsis and may enable personalized medicine approaches. Despite good observational data indicating benefit of sepsis recognition and treatment bundles, the evidence for the individual bundle components remains scarce, implying an urgent need for large trials.

Recent studies have demonstrated distinct epidemiological patterns pertinent to age groups, healthcare settings, and comorbidities in the era post meningococcal epidemics. Although sepsis quality improvement initiatives have led to substantial outcome improvements, there is urgency for innovative trials to reduce uncertainty around the optimal approach for the recognition and treatment of sepsis in children.
Measuring Dynamic CT Perfusion Based on Time-Resolved Quantitative DECT Iodine Maps
Authors: Skornitzke Stephan , Kauczor Hans-Ulrich , Stiller Wolfram
Published: July 2019

Objectives

Using dual-energy computed tomography (DECT) for quantifying iodine content after injection of contrast agent could provide a quantitative basis for dynamic computed tomography (CT) perfusion measurements by means of established mathematical models of contrast agent kinetics, thus improving results by combining the strength of both techniques, which was investigated in this study.

Materials and Methods

A dynamic DECT acquisition over 51 seconds performed at 80/Sn140 kVp in 17 patients with pancreatic carcinoma was used to calculate iodine-enhancement images for each time point by means of 3-material decomposition. After motion correction, perfusion maps of blood flow were calculated using the maximum-slope model from both 80 kVp image data and iodine-enhancement images. Blood flow was measured in regions of interest placed in healthy pancreatic tissue and carcinoma for both of the derived perfusion maps. To assess image quality of input data, an adjusted contrast-to-noise ratio was calculated for 80 kVp images and iodine-enhancement images. Susceptibility of perfusion results to residual patient breathing motion during acquisition was investigated by measuring blood flow in fatty tissue surrounding the pancreas, where blood flow should be negligible compared with the pancreas.

Results

For both 80 kVp and iodine-enhancement images, blood flow was significantly higher in healthy tissue (114.2 ± 37.4 mL/100 mL/min or 115.1 ± 36.2 mL/100 mL/min, respectively) than in carcinoma (46.5 ± 26.6 mL/100 mL/min or 49.7 ± 24.7 mL/100 mL/min, respectively). Differences in blood flow between 80 kVp image data and iodine-enhancement images were statistically significant in healthy tissue, but not in carcinoma. For 80 kVp images, adjusted contrast-to-noise ratio was significantly higher (1.3 ± 1.1) than for iodine-enhancement images (1.1 ± 0.9). When evaluating fatty tissue surrounding the pancreas for estimating influence of patient motion, measured blood flow was significantly lower for iodine-enhancement images (30.7 ± 12.0 mL/100 mL/min) than for 80 kVp images (39.0 ± 19.1 mL/100 mL/min). Average patient radiation exposure was 8.01 mSv for dynamic DECT acquisition, compared with 4.60 mSv for dynamic 80 kVp acquisition.

Discussion

Iodine enhancement images can be used to calculate CT perfusion maps of blood flow, and compared with 80 kVp images, results showed only a small difference of 1 mL/100 mL/min in blood flow in healthy tissue, whereas patient radiation exposure was increased for dynamic DECT. Perfusion maps calculated based on iodine-enhancement images showed lower blood flow in fatty tissues surrounding the pancreas, indicating reduced susceptibility to residual patient breathing motion during the acquisition.
Three Tesla 3D High-Resolution Vessel Wall MRI of the Orbit may Differentiate Arteritic From Nonarteritic Anterior Ischemic Optic Neuropathy
Authors: Mohammed-Brahim Nawel , Clavel Gaëlle , Charbonneau Frédérique , Duron Loïc , Picard Hervé , Zuber Kevin , Savatovsky Julien , Lecler Augustin
Published: July 2019

Background

Anterior ischemic optic neuropathy (AION) is the most common cause of acute optic neuropathy in older patients. Distinguishing between arteritic AION (A-AION) and nonarteritic (NA-AION) is paramount for improved patient management.

Purpose

The aim of this study was to evaluate 3-dimensional high-resolution vessel wall (HR-VW) magnetic resonance imaging (MRI) at 3 T to discriminate A-AION from NA-AION.

Materials and Methods

This prospective single-center study was approved by a national research ethics board and included 27 patients (17 A-AION and 10 NA-AION) with 36 AIONs from December 2014 to August 2017 who underwent 3 T HR-VW MRI. Two radiologists blinded to clinical data individually analyzed the imaging separately and in random order. Discrepancies were resolved by consensus with a third neuroradiologist. The primary diagnostic criterion was the presence of inflammatory changes of the ophthalmic artery. Secondary diagnostic criteria included the presence of an enhancement of the optic nerve or its sheath, the optic disc, or inflammatory changes of posterior ciliary or extracranial arteries. A Fisher exact test was used to compare A-AION from NA-AION patients.

Results

Inflammatory changes of the ophthalmic artery were present in all patients with A-AION but in none of NA-AION (P< 0.0001). Its sensitivity, specificity, positive predictive value, and negative predictive value were 100%. Inflammatory changes of posterior ciliary arteries were significantly more likely in A-AOIN (82% vs 0%,P< 0.0001). Interreader and intrareader agreements were almost perfect (κ = 0.82–1).

Conclusions

High-resolution vessel wall MRI seems highly accurate when distinguishing A-AION from NA-AION and might be useful to improve patient management.
Identification of Patients With Heart Failure From Test Bolus of Computed Tomography Angiography in Patients Undergoing Preoperative Evaluation for Transcatheter Aortic Valve Replacement
Authors: Chaturvedi Abhishek , Chengazi Hamza , Baran Timothy
Published: July 2019

Purpose:

Identify a measurable parameter from test bolus of computed tomography angiography that can differentiate aortic stenosis patients with normal systolic function from those with heart failure and reduced ejection fraction (HFrEF).

Materials and Methods:

This retrospective study included patients (undergoing evaluation for transcatheter aortic valve replacement) who had retrospective electrocardiogram-gated cardiac computed tomography angiography using test bolus. The measured variables were time to peak contrast enhancement in the pulmonary artery (PAtime), in the ascending (AsAotime) and descending aorta (DsAotime). From these, the pulmonary transit time (PTT: difference between time to peak enhancement in the ascending aorta to peak enhancement in the main pulmonary artery), aortic transit time (ATT: difference between time to peak enhancement in the descending aorta to time to peak enhancement in the ascending aorta) and DsAotime−PAtime were also calculated. Biventricular volumes and function were calculated.

The subjects were classified on the basis of ventricular ejection fractions: normal (EF>50%), midrange (EF 40% to 50%), and HF patients with reduced EF (EF<40%). Continuous variables were compared between all groups using ordinary 1-way analysis of variance, while sex was compared using the Fisher exact test. The unpaired t tests were used to compare between the normal and HF groups. Receiver operating characteristic analysis was used in predicting decreased cardiac function (EF<40% vs. EF>50%).

Results:

AsAotime and PTT were significant predictors of low biventricular EF when controlling for sex and body mass index (AsAotime: odds ratio=0.74 [95% confidence interval=0.61-0.91], P=0.005; PTT: odds ratio=0.64 95% confidence interval=0.46-0.88], P=0.006). A threshold of 23 seconds for AsAotime resulted in 72.1% sensitivity and 71.4% specificity, and 79.1% sensitivity and 64.3% specificity for DsAotime.

Conclusions:

The time to peak contrast enhancement from the test bolus images correlates with cardiac function. Decreased biventricular systolic dysfunction can be predicted if the time to peak contrast enhancement is >23 seconds in the ascending or descending aorta.
Postoperative Changes in Lymphoscintigraphic Findings After Lymphaticovenous Anastomosis
Authors: Hara Hisako , Mihara Makoto
Published: July 2019

Background

The surgical result of lymphaticovenous anastomosis (LVA) is usually evaluated using the volume or circumference measurement. The purpose of this study was to elucidate the changes in lymphoscintigraphic findings after LVA.

Methods

We conducted a retrospective study on patients who underwent LVA and preoperative and postoperative lymphoscintigraphy from August 2014 to September 2017. In lymphoscintigraphy, albumin labeled with 99mTc (222 MBq) was injected to the first web space of the foot or the second web of the hands. We evaluated the findings and diagnosed them as “improved” if the extent of dermal backflow was decreased. The clinical symptom was evaluated using circumference measurement and subjective symptoms.

Results

A total of 56 patients (107 limbs) were included. The mean age was 59.1 years. The mean period between LVA and postoperative lymphoscintigraphy was 437.0 days. The difference between preoperative and postoperative lymphoscintigraphic types in Maegawa classification was not found to be statistically significant on the χ2 test (P = 0.36). The lymphoscintigraphic findings were improved in 26 limbs (24.3%), did not change in 43 limbs (40.2%), and were aggravated in 38 limbs (35.5%). Among the 22 limbs whose lymphoscintigram improved postoperatively, 9 limbs (40.9%) improved in clinical symptoms.

Conclusions

The changes in clinical symptoms and the postoperative lymphoscintigraphic changes did not always correspond. However, there was a tendency for the percentage of lymphoscintigraphic aggravation to be higher in the group with clinical aggravation.
Cell-Based Therapies for Chronic Wounds Tested in Clinical Studies
Authors: Domaszewska-Szostek Anna , Krzyżanowska Marta , Siemionow Maria
Published: July 2019

Introduction

Transplantation of the keratinocytes, fibroblasts, bone marrow, and adipose tissue–derived mesenchymal stem cells may improve chronic wound healing by delivery of different cytokines, chemokines, and growth factors, which play an essential role in wound healing. The purposes of this review were to check which cell lines are potentially beneficial in enhancement of wound healing and to describe the safety and efficacy of cell therapies in the clinical treatment of chronic wounds, as well as to summarize the pertinent literature and research progress in this field.

Methods

PubMed search engine and ClinicalTrials.gov were used to analyze the available data on cell therapies applied in treatment of chronic wound. The analysis included 51 articles, assessing the use of keratinocytes (10), fibroblasts (7), keratinocytes and fibroblasts (10), bone marrow–derived cells (20), and adipose tissue cells (4). Studies on the cell-based products that are currently available on the market (Dermagraft, EpiDex, Apligraf, and HP802-247) were also included, with majority of reports found on fibroblasts and keratinocytes studies.

Results

Cell-based therapies have a great potential to improve wound healing without major surgical procedures and donor-site morbidity. There is, however, a lack of guidelines on how the age of the patients, the general health conditions, and the coexistence of different diseases may affect the success of these therapies. Further studies are needed to determine the fate of transplanted cells and the number of cells required to obtain optimal effects and outcomes.

Conclusions

Despite many promising clinical trials on application of various stem cell–based therapies for treatment of chronic wounds, there is still a need for multicenter comparative studies assessing the dose response and the cell source response on the efficacy of chronic wound healing.
Clinical Anatomy of Submental Intubation
Authors: Jacob DeAsia D. , Tuncer Fatma B. , Kashan David L. , Gurunluoglu Raffi
Published: July 2019

Since its original description in 1986 by Hernandez, submental intubation has been used in a wide variety of craniomaxillofacial cases as a way to satisfy both surgeon and anesthesiologist to provide access to necessary surgical sites and airway protection. Many modifications to the original technique have been described. There has been a paucity of plastic surgery literature over the last 10 years that have reviewed the anatomy, technique, and complications. In this article, the authors review the pertinent anatomy related to this method of intubation. A cadaver was used to enhance visualization of important structures and to show the modification used by our group. Submental intubation provides a useful alternative to tracheostomy in several craniomaxillofacial procedures. Our approach uses a reinforced endotracheal tube to prevent kinking and provide additional intraoperative protection of the airway. Submental intubation may be indicated in select patients undergoing craniomaxillofacial surgery. Therefore, it is pertinent to be aware of the important anatomy and the complications of this technique to appropriately counsel patients. Our modification provides safe airway control.
Toe-to-Hand Transfer in an Ulnar Hemimelia Patient
Authors: Sönmez Erhan , Aksam Ersin
Published: July 2019

Ulnar hemimelia is a rare congenital deformity. The severity of the deformity increases with the number of fingers that are absent. Clearly, grip function is impossible with a mono-finger hand. Here, we present a case report of a patient with bilateral ulnar hemimelia that included the absence of radial fingers and also deformity in the toes of his left foot. A toe-to-hand transfer was performed successfully to help the patient gain grip function. Both the patient and the parents were very pleased with the result. To our knowledge, this is the first case report of a patient with ulnar hemimelia and absent radial fingers who was treated with a toe-to-hand transfer.

The most important factors in a successful surgery are careful preoperative planning and microsurgical expertise. Angiography is the key to careful planning, and physiotherapy should also be done to increase the patient's functions. The psychological well-being of patients and parents will be positively affected after a successful surgery.
Mid-Term Outcome of Mandibular Distraction Osteogenesis in Pierre Robin Sequence
Authors: Konofaos Petros , Puente-Espel Jordi , Askandar Sameh , Wallace Robert D.
Published: July 2019

The aim of the present study was to present a single center's experience with mandibular distraction osteogenesis (MDO) in Pierre Robin sequence (PRS) patients. A retrospective chart review was performed to identify patients with PRS that underwent MDO at our institution from 2003 to 2012. Inclusion criteria were as follows:

Evaluation included demographic information, postoperative complications, and surgical outcomes. Twenty-four patients met the inclusion criteria. No complications related to our distraction technique were reported. Most of the patients who had a tracheostomy were successfully decannulated and the rest were able to avoid a tracheostomy. Two patients had superficial infections that were treated conservatively with topical antibiotics. One patient, who was our first case in the series, required 3 episodes of distraction osteogenesis. Another patient demonstrated recurrent symptoms of obstructive sleep apnea after MDO and was treated with continuous positive airway pressure. Over-correction during MDO in PRS is an efficient method for preventing future airway problems. Patients who required a tracheotomy pre-distraction and cases in whom distraction was performed at older age (>2 months of age), had a lower success rate in achieving de-cannulation and a higher rate of complications. Laryngomalacia, gastro-esophageal reflux disease, cardiac, and GI anomalies are not associated with increased failure rates of MDO in PRS.
A Pilot Study Assessing the Incidence of Chronic Sinusitis Following Le Fort I Osteotomy in Maxillofacial Surgery
Authors: Eliason Michael J. , Capra Gregory , LaBanc Austin , Braxton Jeanelle , Hamersley Erin , Radabaugh Jeffrey Paul
Published: July 2019

Orthognathic surgery utilizing a Le Fort I osteotomy is performed regularly by oral surgeons to correct midface and dental occlusal abnormalities, yet little has been written discussing the impact these operations may have on sinonasal function. The objective of this study was to assess the incidence of objective sinonasal inflammation and subjective sinonasal symptoms following the use of Le Fort I osteotomies for maxillary advancement surgery.

Thirty-eight subjects who previously underwent Le Fort I osteotomies for purposes of elective orthognathic surgery were enrolled retrospectively to assess for evidence of rhinosinusitis (RS). Post-operative and, when available, preoperative maxillofacial computed tomography (CT) scans were obtained and evaluated using Lund Mackay scoring (LMS). The Chronic Sinusitis Survey – Duration Based (CSS-D) was completed to compare subjective symptoms before and after surgery.

Evaluation of the CT scans demonstrated radiographic evidence of RS and subjective worsening of symptoms in 87% and 89% respectively. The mean CSS-D pre- and post-operative scores were 7.6 and 14.8 respectively (P < 0.0001). The mean calculated LMS was 3.39 (2.38–4.40, 95% C.I.). Further sub-analyses demonstrate an increase in both radiographic LMS and subjective CSS-D for patients who had persistent inferior meatal antrostomies after Le Fort I osteotomy.

Le Fort I osteotomies performed during orthognathic surgery result in a higher prevalence of post-operative RS than what has been previously described. A better understanding of sinonasal mucocilliary function and the aberrancy that may be caused following such operations deserves further evaluation in order to identify and optimize postsurgical outcomes.