Issue Information

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Continuing Professional Development Quiz

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The ADJ in 2019 – is it relevant?

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Rural solid waste—characteristics and leachate pollution assessment for different precipitation levels, China

Abstract

Open dumping adversely affects the environment and remains the most widely used method for waste disposal in many developing rural areas in China. Information regarding the impact of rural solid waste (RSW) on the environment remains limited. The objectives of this study are to investigate the characteristics of RSW and the impact of different precipitation rates, and to evaluate the contamination potential of RSW using a leachate pollution index (LPI). The study showed that leachate concentration was significantly influenced by precipitation rates at the initial precipitation stages. Precipitation rates of 42.00 mm/day appeared to have the largest dilution effects. In contrast, the concentrations of leachate at rainfall rates of 24.00 mm/day and soaking were steady, and no similar trends were observed. The highest amounts of pollutants in leachate were the result of soaking. In the first week of our experiment, the LPI value for each rural area waste sample rapidly increased with rising precipitation rates from soaking to 42.00 mm/day. However, no significant change in LPI was observed thereafter (after 5 weeks) even with increasing precipitation rates. The values of chemical oxygen demand, biochemical oxygen demand, total nitrogen, and NH₃-N in the leachate after 10 weeks were 4.00, 7.34, 1.87, and 2.21 times higher, respectively, than those of the prescribed leachate quality standards in China. The results of our study suggest the following course of action for the three dump sites investigated: in Banqiao, given the size of the population and the size of the waste amount, landfill might be a suitable way for disposing of RSW. In Machen, building a standardized waste collection site would be an economical solution for reducing potential pollution risks. In Jiuduhe, increasing the transportation rate of solid waste might be an effective solution. The results of this study can help to improve the understanding of leachate pollution in Chinese rural areas.

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Accuracy of crowns based on digital intraoral scanning compared to conventional impression—a split-mouth randomised clinical study

Abstract

Objectives

The aim of this prospective in vivo study was to evaluate the accuracy of the marginal and internal fit of crowns based on conventional impression (CI) or intraoral scan (IOS) in a randomised, split-mouth set-up.

Materials and methods

Nineteen patients needing full coverage crowns, fitting a split-mouth design, were provided with two lithium disilicate crowns: one based on a CI and one based on an IOS. The marginal and internal accuracy of the crowns were assessed with the replica technique and clinically using a modified California Dental Association (CDA) quality evaluation system.

Results

At the preparation margin, the median gap was 60 μm for IOS and 78 μm for CI. For the other points, the median gap ranged from 91 to 159 μm for IOS and 109 to 181 μm for CI. The accuracy of the IOS was statistically significantly better at all point except at the cusp tip. All crowns where rated R or S at both the 6- and 12-month follow-up appointments. The results for the clinical evaluation with CDA for marginal integrity showed no statistically significant difference between the two impression methods at both the 6- and 12-month evaluations.

Conclusions

Crowns based on IOS show statistically significantly better marginal and internal adaptation before cementation compared to conventional impression. However, the clinical evaluation showed similar marginal adaptation.

Clinical relevance

Crowns based on a fully digital workflow can provide clinically acceptable marginal adaptation, comparable to crowns based on CI.

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Ecotoxicological assessments of biochar additions to soil employing earthworm species Eisenia fetida and Lumbricus terrestris

Abstract

Biochar is the degradation-resistant product generated by the pyrolysis of organic materials and is produced for the intended use of land application in order to promote carbon sequestration and soil improvement. However, despite the many potential benefits biochar application offers, it is important to quantify any ecological impacts that may result from soil amendment in order to avoid potentially causing negative effects upon soil biota which are crucial in the many ecosystem services provided by soil. Any impacts on earthworms in particular are important to evaluate because of their pivotal role in organic matter breakdown, nutrient cycling and soil formation. In this study, we conducted a series of ecotoxicological assays to determine lethal and sublethal (avoidance, mass change and moisture content) effects of heavy biochar applications that reflect levels that may be used in soil restoration efforts. Two earthworm species, Eisenia fetida, an epigeic species, and Lumbricus terrestris, an anecic species, were utilised as test organisms. Two types of biochar, produced from wheat straw and rice husk feedstocks, respectively, were applied to OECD artificial soil and to a natural soil (Kettering loam) at rates of up to 20% w/w. The influence of biochar application on soil porewater chloride, fluoride and phosphate concentrations was also assessed. The biochar applications induced only a subtle level of avoidance behaviour while effects on survival over a 4-week exposure period were inconsistent. However, death and physical damage to some individual earthworms at high biochar application rates were observed, the mechanisms and processes leading to which should be investigated further. Earthworm development (mean mass change over time) proved to be a more sensitive measure, revealing negative effects on L. terrestris at 10% and 20% (w/w) wheat biochar applications in OECD soil and at 20% (w/w) applications of both biochars in Kettering loam. The moisture content of E. fetida remained remarkably consistent across all treatments (~ 82%), indicating that this is not a sensitive measure of effects. The high rates of biochar application resulted in increased chloride (2 to 3-fold) and phosphate (100-fold) concentrations in simulated soil porewaters, which has important implications for soil fertility and production but also for environmental management.

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Investigating the nexus among environmental pollution, economic growth, energy use, and foreign direct investment in 6 selected sub-Saharan African countries

Abstract

This research seeks to enhance the current literature by exploring the nexus among environmental contamination, economic growth, energy use, and foreign direct investment in 6 selected sub-Saharan African nations for a time of 34 years (1980–2014). By applying panel unit root (CADF and CIPS, cross-sectional independence test), panel cointegration (Pedroni and Kao cointegration test, panel PP, panel ADF), Hausman poolability test, and an auto-regressive distributed lag procedure in view of the pooled mean group estimation (ARDL/PMG), experimental findings disclose that alluding to the related probability values, the null hypothesis of cross-sectional independence for all variables is rejected because they are not stationary at levels but rather stationary at their first difference. The variables are altogether integrated at the same order I(1). Findings revealed that there is a confirmation of a bidirectional causality between energy use and CO₂ in the short-run and one-way causality running from energy use to CO₂ in the long run. There is additionally a significant positive outcome and unidirectional causality from CO₂ to foreign direct investment in the long run yet no causal relationship in the short run. An increase in energy use by 1% causes an increase in CO₂ by 49%. An increase in economic growth by 1% causes an increment in CO₂ by 16% and an increase in economic growth squared by 1% diminishes CO₂ by 46%. The positive and negative impacts of economic growth and its square approve the EKC theory. To guarantee sustainable economic development goal, more strict laws like sequestration ought to be worked out, use of sustainable power source ought to be stressed, and GDP ought to be multiplied to diminish CO₂ by the utilization of eco-technology for instance carbon capturing, to save lives and also to maintain a green environment.

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Clinical Infectious Diseases

The Association of Antibiotic Stewardship With Fluoroquinolone Prescribing in Michigan Hospitals: A Multi-hospital Cohort Study Abstract Background Fluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown. Methods This study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship. Results There were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003). Conclusions Hospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing.

Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF–identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012–2017: A Retrospective Province-Wide Cohort Study Abstract Background Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. Results Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71). Conclusions Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes. The Association of Antibiotic Stewardship With Fluoroquinolone Prescribing in Michigan Hospitals: A Multi-hospital Cohort Study Abstract Background Fluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown. Methods This study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship. Results There were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003). Conclusions Hospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing. Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF–identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012–2017: A Retrospective Province-Wide Cohort Study Abstract Background Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. Results Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71). Conclusions Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes. Glycocalyx Breakdown is Associated with Severe Disease and Fatal Outcome in Plasmodium falciparum Malaria Abstract Background Interactions between the endothelium and infected erythrocytes, microvascular dysfunction and parasite sequestration play major roles in the pathogenesis of severe falciparum malaria. The glycocalyx is a carbohydrate-rich layer lining the endothelium mediating NO production and vascular homeostasis. The role of the glycocalyx in falciparum malaria and the association with disease severity is not known. Methods We prospectively enrolled Indonesian inpatients (≥18 years old) with severe (SM) or moderately-severe (MSM) falciparum malaria and healthy controls (HCs). Glycocalyx breakdown products were measured in enrolment samples of urine (glycosaminoglycans; dimethylmethylene blue [GAG-DMMB] and liquid chromatography-tandem mass spectrometry [GAG-MS] assays) and plasma (syndecan-1; ELISA), and related to vascular NO bioavailability (reactive hyperemia-peripheral arterial tonometry). Results A total of 129 subjects (SM=43, MSM=57, HC=29) were recruited. Syndecan-1 (µg/ml), GAG-DMMB and GAG-MS (g/mol creatinine) were increased in SM [median (range) 332.4 (85-3-1913), 3.16 (0.04-27.9) and 4.73 (2.02-27.13)] compared to MSM [99.1 (19.9-767.6), 1.28 (0.03-9.3) and 4.44 (1.19-13.87)], and HCs [48.9 (32.3-88.3), 0.11 (0.02-1.9) and 2.55 (0.73-10.19)]; P<0.001. In SM, GAG-DMMB and GAG-MS were increased in non-survivors (n=3) [median (IQR): 6.72 (3.80-27.87) and 12.15 (7.88-17.20)] compared to survivors n=39 [(3.10 (0.46-4.5) and 4.64 (2.02-15.20)]; P=0.03. Glycocalyx degradation was associated with parasite biomass in MSM (r=0.31, P=0.03 [syndecan-1]; r=0.48 [GAG-DMMB] and r=0.43 [GAG-MS], P<0.001), and SM patients (r=0.29, P=0.04, r=0.47; P=0.002 and r=0.33, P=0.04), and inversely associated with endothelial NO bioavailability. Conclusions Increased endothelial glycocalyx breakdown is associated with impaired vascular NO, severe disease and fatal outcome in adults with falciparum malaria, likely contributing to pathogenesis. Impact of rotavirus vaccine introduction in children less than 2 years of age presenting for medical care with diarrhea in rural Matlab, Bangladesh Abstract Background Following the conclusion of a Rotarix vaccine (HRV) cluster-randomized controlled trial (CRT) in Matlab, Bangladesh, HRV was included in Matlab's routine immunization program. We describe the population-level impact of programmatic rotavirus vaccination in Bangladesh in children <2 years of age Methods Interrupted time series were used to estimate the impact of HRVintroduction. Diarrheal surveillance collected between 2000 and 2014 within the two service delivery areas (icddr,b service area [ISA] and government service area [GSA]) of the Matlab Health and Demographic Surveillance System administered by icddr,b was used. Age-group specific incidence rates were calculated for both rotavirus-positive (RV+) and rotavirus-negative (RV-) diarrhea of any severity presenting to the hospital. Two models were used to assess impact within each service area: Model 1 used the pre-vaccine time period in all villages (HRV- and control-only) and Model 2 combined the pre-vaccine time period and the CRT time period using outcomes from control-only villages. Results Both models demonstrated a downward trend in RV+ diarrheal incidence in the ISA villages during 3.5 years of routine HRV use, though only Model 2 was statistically significant. Significant impact of HRV on RV+ diarrhea incidence in GSA villages was not observed in either model. Differences in population-level impact between the two delivery areas may be due to varied rotavirus vaccine coverage and presentation rate to the hospital. Conclusions This study provides initial evidence of the population-level impact of rotavirus vaccines in children <2 years of age in Matlab, Bangladesh. Further studies of rotavirus vaccine impact after nationwide introduction in Bangladesh are needed. Transmission-blocking effects of primaquine and methylene blue suggest P. falciparum gametocyte sterilisation rather than effects on sex ratio Abstract Gametocyte density and sex-ratio can predict the proportion of mosquitoes that become infected after feeding on blood of patients receiving non-gametocytocidal drugs. Because primaquine and methylene blue sterilize gametocytes before affecting their density and sex-ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects. Principal Controversies in Vaccine Safety in the United States Abstract Concerns about vaccine safety can lead to decreased acceptance of vaccines and resurgence of vaccine-preventable diseases. We summarize the key evidence on some of the main current vaccine safety controversies in the United States, including: 1) MMR vaccine and autism; 2) thimerosal, a mercury-based vaccine preservative, and the risk of neurodevelopmental disorders; 3) vaccine-induced Guillain-Barré Syndrome (GBS); 4) vaccine-induced autoimmune diseases; 5) safety of HPV vaccine; 6) aluminum adjuvant-induced autoimmune diseases and other disorders; and 7) too many vaccines given early in life predisposing children to health and developmental problems. A possible small increased risk of GBS following influenza vaccination has been identified, but the magnitude of the increase is less than the risk of GBS following influenza infection. Otherwise, the biological and epidemiologic evidence does not support any of the reviewed vaccine safety concerns. Insertion as resistance mechanism against integrase inhibitors in several retroviruses Birth Cohort Studies Assessing Norovirus Infection and Immunity in Young Children: A Review Abstract Globally, noroviruses are among the foremost causes of acute diarrheal disease, yet there are many unanswered questions on norovirus immunity, particularly following natural infection in young children during the first 2 years of life when the disease burden is highest. We conducted a literature review on birth cohort studies assessing norovirus infections in children from birth to early childhood. Data on infection, immunity, and risk factors are summarized from 10 community-based birth cohort studies conducted in low- and middle-income countries. Up to 90% of children experienced atleast one norovirus infection and up to 70% experienced norovirus-associated diarrhea, most often affecting children 6 months of age and older. Data from these studies help to fill critical knowledge gaps for vaccine development, yet study design and methodological differences limit comparison between studies, particularly for immunity and risk factors for disease. Considerations for conducting future birth cohort studies on norovirus are discussed. In the Literature Saddle Nose Deformity in an Immunosuppressed Patient Cover News Ebola's Curse: 2013–2016 Outbreak in West Africa By OldstoneMichael and OldstoneMadeleine. Elsevier, 2017. 126 pp. $89.95 (hardcover). ISBN: 9780128138885. Cost-effectiveness and Cost-utility of the Adherence Improving Self-management Strategy in Human Immunodeficiency Virus Care: A Trial-based Economic Evaluation Abstract Background Several promising human immunodeficiency virus (HIV) treatment adherence interventions have been identified, but data about their cost-effectiveness are lacking. This study examines the trial-based cost-effectiveness and cost-utility of the proven-effective Adherence Improving Self-Management Strategy (AIMS), from a societal perspective, with a 15-month time horizon. Methods Treatment-naive and treatment-experienced patients at risk for viral rebound were randomized to treatment as usual (TAU) or AIMS in a multicenter randomized controlled trial in the Netherlands. AIMS is a nurse-led, 1-on-1 self-management intervention incorporating feedback from electronic medication monitors, delivered during routine clinical visits. Main outcomes were costs per reduction in log10 viral load, treatment failure (2 consecutive detectable viral loads), and quality-adjusted life-years (QALYs). Results Two hundred twenty-three patients were randomized. From a societal perspective, AIMS was slightly more expensive than TAU but also more effective, resulting in an incremental cost-effectiveness ratio (ICER) of €549 per reduction in log10 viral load and €1659 per percentage decrease in treatment failure. In terms of QALYs, AIMS resulted in higher costs but more QALYs compared to TAU, which resulted in an ICER of €27759 per QALY gained. From a healthcare perspective, AIMS dominated TAU. Additional sensitivity analyses addressing key limitations of the base case analyses also suggested that AIMS dominates TAU. Conclusions Base case analyses suggests that over a period of 15 months, AIMS may be costlier, but also more effective than TAU. All additional analyses suggest that AIMS is cheaper and more effective than TAU. This trial-based economic evaluation confirms and complements a model-based economic evaluation with a lifetime horizon showing that AIMS is cost-effective. Clinical Trials Registration NCT01429142 First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient Abstract Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus–1 Infection: Week 48 Results of the DRIVE-AHEAD Trial Abstract Background Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile. Methods DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment–naive adults with ≥1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%). Results Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved <50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) (-3.83 vs +13.26 mg/dL) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (−1.6 vs +8.7 mg/dL and −3.8 vs +13.3 mg/dL, respectively). Conclusions In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non–HDL-C compared with EFV/FTC/TDF. Clinical Trials Registration NCT02403674 A 44-Year-Old Female With Overwhelming Sepsis sepsisaspleniaRPSA geneHowell-Jolly bodiesStreptococcus pneumonia Concurrent Seroprevalence of Antibodies to Toxoplasma gondii and Toxocara Species in the United States, 2011–2014 To the Editor—We report supplemental findings incorporating Toxoplasma gondii serology results from our study of risk factors for Toxocara seropositivity in the United States [1] using stored serum samples collected from the National Health and Nutrition Examination Survey (NHANES), 2011–2014. Whereas T. gondii is a protozoan parasite and Toxocara is an intestinal nematode, both share ingestion of contaminated soil as means of exposure in humans. Both parasites can contaminate soil when environmentally resistant T. gondii oocysts or Toxocara cati eggs are shed in the feces of infected cats [2, 3].

Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection Abstract Recognizing the importance of timely guidance regarding the rapidly evolving field of hepatitis C management, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) developed a web-based process for the expeditious formulation and dissemination of evidence-based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance website undergoes periodic updates as necessitated by availability of new therapeutic agents and/or research data. A major update was released electronically in September 2017, prompted primarily by approval of new direct-acting antiviral agents and expansion of the guidance's scope. This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication. The recommendations herein were developed by volunteer hepatology and infectious disease experts representing AASLD and IDSA and have been peer reviewed and approved by each society's governing board.

Combined use of biochar and zinc oxide nanoparticle foliar spray improved the plant growth and decreased the cadmium accumulation in rice ( Oryza sativa L.) plant

Abstract

The contamination of large areas of arable land with cadmium (Cd) is a serious concern worldwide and environmentally feasible amendments are necessary to minimize Cd accumulation in cereals such as rice (Oryza sativa L.). A pot study was, therefore, conducted to evaluate the efficiency of foliar spray of different levels (0, 50, 75, 100 mg/L) of zinc oxide nanoparticles (ZnO NPs) alone or combined with biochar (1.0% w/w) on Cd content in rice plants grown on an aged Cd-polluted soil. The results showed that ZnO NPs alone or combined with biochar improved the biomass and photosynthesis of rice plant. The ZnO NPs significantly diminished the Cd concentration and enhanced the Zn concentrations in shoots and roots either alone or in combination with biochar. Foliar spray of 100 mg/L ZnO NPs significantly diminished the Cd content in rice shoot and rice roots by 30% and 31%, respectively. The Cd concentrations in rice shoot and root diminished by 39% and 38% after 100 mg/L ZnO NPs combined with biochar, respectively. The ZnO NPs in combination with biochar increased the soil pH from 8.03 to 8.23 units. Soil AB-DTPA-extractable Cd significantly reduced with the amendments applied over the control. Foliar spray of ZnO NPs combined with biochar could be used to grow rice plants especially in areas where Cd concentration is high and Zn deficiency is high.

https://ift.tt/2V6aFu2

External root resorption in maxillary and mandibular second molars associated with impacted third molars: a cone-beam computed tomographic study

Abstract

Objective

To separately investigate the prevalence and risk factors of external root resorption (ERR) in maxillary and mandibular second molars (M2s) adjacent to impacted third molars (M3s).

Materials and methods

CBCT scans involving 184 maxillary and 323 mandibular impacted M3s were included. Age, gender, the impaction status of M3, the presence, severity, and location of ERR in M2 were assessed. Risk factors were identified by multivariate logistic regression analyses.

Results

The prevalence of ERR was 32.6% in maxillary and 52.9% in mandibular M2s (P < 0.001). Mesio-angulated and deeply impacted M3s were identified as risk factors for both ERR in maxillary and mandibular M2s (P < 0.05). Besides, age over 25 increased the risk of ERR in maxillary M2s (P < 0.05). ERR in maxillary M2s was overall more severe than that in mandibular M2s (P < 0.001). For maxillary M2s, ERR mostly occurred at the apical third, while the mandibular M2s ERR was most frequently detected at the cervical third.

Conclusions

ERR occurring in M2s adjacent to impacted M3s is common, especially in mandibular M2s. ERR in maxillary M2s cannot be neglected because of its relatively high severity. Mesial angulation and impaction depth of M3 are significantly associated with ERR in M2s. For ERR in maxillary M2s, age is another predictive parameter.

Clinical relevance

Considering the presence of ERR is associated with M3s' impaction, watchful monitoring or prophylactic removal of impacted M3s should be deliberated especially for the patients over 25 years and with mesially inclined and deeply positioned M3s.

https://ift.tt/2GHDbiq

Expression of Wnt‐1 and TSLC1 in condyloma acuminatum

Summary

Background

Despite its high contagiousness, high recurrence rate and potential for malignant transformation, effective treatments for condyloma acuminatum (CA) have not yet been developed. Accordingly, it is necessary to clarify the mechanisms underlying CA development.

Aim

To investigate the expression and significance of the proteins Wnt‐1 and TSLC1 in patients with CA and in normal foreskin controls.

Methods

Wnt‐1 and TSLC1 were assessed by immunohistochemistry in 45 patients with CA.

Results

Positive expression rates of Wnt‐1 and TSLC1 were 82.22% (37/45) and 37.78% (17/45), respectively, in CA tissues, and 29.17% (7/24) and 91.67% (22/24), respectively, in normal foreskin controls. Wnt‐1 expression intensity in CA was markedly higher (positive to strongly positive) than that in normal controls (negative to weakly positive), whereas TSLC1 expression intensity ranged from weakly positive to positive in CA, and nearly strongly positive in the normal control group. The differences in the positive expression rate and expression intensity of Wnt‐1 and TSLC1 between the two groups were statistically significant (P < 0.05). In addition, Wnt‐1 and TSLC1 were negatively correlated. (r = −0.336, P < 0.05).

Conclusions

Overexpression of Wnt‐1 and low expression of TSLC1 may be associated with the growth of CA. These findings may provide a basis for the development of therapies to prevent recurrence or malignant transformation of CA.

https://ift.tt/2GEn2ug

Nail cosmetics: a dermatological perspective

Summary

Nail cosmetics are used by millions worldwide and the variety of products available is expanding. They are relatively safe, but complications can occur, and patients experiencing complications may present to dermatologists. The physical processes can cause nail thinning and onycholysis, poor technique can promote infection, and consumers may develop allergic contact dermatitis. Ultraviolet nail lamps are widely used for curing gel nails, but their use is unregulated and they are readily accessible in salons or for home use. There is concern about potential carcinogenesis; however, the risk is negligible and can be further reduced with the use of sunscreen. Despite the potential complications, nail cosmetics may be a useful adjunct in treating nail disorders. Familiarity with the procedures will enable the dermatologist to recognize problems and advise on safe use.

https://ift.tt/2NlzuiN

The efficacy of combined diluted calcium hydroxylapatite‐based filler and an energy‐based device in the treatment of facial atrophic acne scars

Abstract

Background and Objectives

Treatment options for atrophic acne scars include the use of various energy‐based devices (EBDs) and dermal fillers.

Aim

To evaluate the level of improvement and safety of four treatment modalities for atrophic acne scars employed in our center.

Methods

We reviewed the medical records of all acne scar patients treated between 2013‐2016 with one of four treatment modalities: ablative fractional CO2 laser (FACL), the radiofrequency (RF) bipolar device, the 1540 nm non‐ablative fractional laser (NAFL), and the injection of diluted calcium hydroxylapatite (CaHA). The EBDs were used as monotherapy or in combination with diluted CaHA. Two non‐involved dermatologists and the patients evaluated the aesthetic improvement achieved following the various modalities. The patients also rated their satisfaction, numbered the days of post‐treatment downtime, and reported any adverse effects.

Results

In total, 352 patients (mean age 28.7±8.7, 65.6% females) were treated for acne scars. The integrated mean dermatologists' and patients' GAS scores were the highest for the patients treated with the combined FACL‐CaHA modality at separate sessions (P < 0.001). Patients treated with FACL reported more side effects and longer downtime and duration of erythema.

Conclusions

The combination of a diluted CaHA‐based filler injection followed by fractional ablative CO2 laser in separate treatment sessions yielded better aesthetic improvement compared to the other tested modalities.

This article is protected by copyright. All rights reserved.

https://ift.tt/2GDtlxZ

Effect of cation type in mixed Ca-Na systems on transport of sulfonamide antibiotics in saturated limestone porous media

Abstract

Retention and transport of sulfonamides (SAs) in subsurface can strongly affect groundwater quality. In this work, a range of laboratory batch sorption and column transport experiments were conducted to determine the effect of cation type in mixed Ca-Na systems on the retention and transport of two typical SAs, sulfadimethoxine (SDM) and sulfacetamide (SCA), in saturated limestone porous media. Column experimental data showed divalent cation Ca²⁺ played a more important role than monovalent cation Na⁺ in decreasing the transport of only SDM in co-cation systems in the saturated limestone media. Further, in the single-cation (i.e., including either Ca²⁺ or Na⁺) system, increasing ionic strength (IS) of either NaCl or CaCl₂ had little effect on SCA transport; however, increasing of IS of CaCl₂ promoted the retention of SDM in the saturated limestone porous media. This is mainly due to the cation bridging effect of Ca²⁺ on SDM and limestone. Overall, SDM showed much higher retention in the limestone columns than SCA, which can be attributed to the two SAs' different physicochemical properties. Moreover, limestone showed stronger ability to retain the two SAs than quartz sand. Findings in this study suggest that cation type and the concentration of certain electrolyte (e.g., CaCl₂) as well as medium type play an important role in controlling the environmental fate and transport of antibiotics.

https://ift.tt/2GCVkxL

Living with vulval lichen sclerosus: a systematic review

Abstract

Lichen sclerosus (LS) is an under‐researched disorder, particularly from the perspective of individuals who have the condition. A recent James Lind Alliance Priority Setting Partnership identified uncertainties in many aspects of the condition, including its impact on quality of life which was ranked within the 'Top 10' future research priorities.^1,2 We set out to systematically review the qualitative literature exploring the lived experience of vulval LS (for the full protocol see PROSPERO ID:CRD42018106947)

This article is protected by copyright. All rights reserved.

https://ift.tt/2VaHvK8

Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment: a pooled analysis of data from 2 phase III trials

Summary

Background

In the US, an Investigator's Global Assessment (IGA) score of ≤ 1 (clear/almost clear skin) has been the regulatory outcome standard measure for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab.

Objective

To evaluate the treatment effect of dupilumab in patients with IGA>1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life.

Methods

LIBERTY AD SOLO 1 and 2 were two 16‐week, randomized, double‐blind trials enrolling adult patients with moderate‐to‐severe AD (IGA≥3) inadequately controlled with topical treatment. We performed a post‐hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA>1 included Eczema Area and Severity Index (EASI), pruritus Numerical Rating Scale (NRS), affected Body Surface Area (BSA), Patient‐Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI).

Results

At Week 16, 278/449 dupilumab q2w‐treated patients (median age 36·0 years) and 396/443 placebo‐treated patients had IGA>1. Among patients with IGA>1 at Week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (–48·9% vs. –11·3%, P<0·001), pruritus NRS (–35·2% vs. –9·1%, P < 0·001), BSA affected (–23·1% vs. –4·5%, P<0·001), POEM score ≥ 4‐point improvement (57·4% vs. 21·0%, P<0·001), and DLQI score ≥ 4‐point improvement (59·3% vs. 24·4%, P<0·001).

Conclusions

In patients with IGA>1 at Week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures versus placebo. The IGA≤1 endpoint significantly underestimates clinically relevant dupilumab treatment effects.

This article is protected by copyright. All rights reserved.

https://ift.tt/2Emc2z2

Chemoradiotherapy could improve overall survival of patients with stage IV cutaneous squamous cell carcinoma: analysis of 34 cases

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common non‐melanoma skin cancer, comprising approximately 20% of all skin malignancies¹. The prognoses of patients with unresectable disease, such as locally advanced tumour or distant metastases, are known to be relatively poor due to lack of effective standardized systemic therapies^2,3. When surgery is not feasible, non‐surgical approaches such as chemotherapy, radiation therapy (RT), and chemoradiotherapy (CRT; chemotherapy with radiation), are considered as alternative treatments².

This article is protected by copyright. All rights reserved.

https://ift.tt/2T7jpmi

Serum cytokeratin 19 fragment 21‐1 and carcinoembryonic antigen combination assay as a biomarker of tumour progression and treatment response in extramammary Paget's disease

Summary

Background

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma affecting the genitals and axillary regions. As metastasis of these tumours is itself rare, solid disease management strategies have not been established. Serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 21‐1 (CYFRA 21‐1) levels have been identified as candidate biomarkers for tumour progression in EMPD; however, neither the accuracy of, nor correlation between, these markers have been examined in EMPD patients.

Methods

Serum CEA and CYFRA 21‐1 levels were examined in 30 EMPD patients treated at Keio University Hospital, and compared against clinical information retrospectively. Both assays were performed at the time of diagnosis, during the postoperative observation period, and following systemic treatment in those with confirmed metastasis. Serum levels were then correlated with tumour progression status and treatment responses.

Results

Normal levels for both assays were observed in all 11 primary localised patients (100%). In metastatic patients, the CEA positivity rate was 78·9% (15/19 patients) and 63·1% (11/19 patients) for CYFRA 21‐1. Changes in CEA and CYFRA 21‐1 levels were statistically independent; however, using a combined view, elevated levels of either marker improved the positivity rate to 94·8% (18/19 patients). Use of both markers also correlated well with the treatment responses.

Conclusions

The combination of CEA and CYFRA 21‐1 is useful for predicting metastasis and treatment response in EMPD patients, especially in those who only have elevation of a single marker.

This article is protected by copyright. All rights reserved.

https://ift.tt/2IsWei0

Tertiary Breast Reconstruction for Salvage of the Failed Implant-Based Reconstruction Using the Deep Inferior Epigastric Perforator Flap

J reconstr Microsurg
DOI: 10.1055/s-0039-1679885

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2tzcbsJ

Flap Reconstruction of Gastrointestinal-to-Genitourinary Fistulas: A 20-Year Experience

J reconstr Microsurg
DOI: 10.1055/s-0039-1679880

Background Gastrointestinal-to-genitourinary fistulas may occur secondary to obstetric complications, radiation therapy, cancer without radiation, inflammatory bowel disease, or previous surgery. Flap reconstruction is useful for complex cases refractory to standard techniques, separating the fistula tracts to aid healing. The purpose of this study was to investigate outcomes and risk factors for complications in flap reconstruction of fistulas from several different etiologies performed over a 20-year period. Methods All patients who underwent flap reconstruction between January 1995 and December 2014 were reviewed. Patient demographics, prior treatment failures, surgical indications, and comorbidities were obtained. Operative and postoperative data were collected, including flap type, length of stay, early and late complications, recurrences, and follow-up time. Operative success was defined as definitive treatment of the fistula without recurrence within 6 months. Results There were 59 patients who underwent 66 reconstructions. The overall complication rate was 59.1%. Complications included infection (21%), dehiscence (17%), and partial flap loss (1.5%). Operative success rate was 51.5%. Smoking history (p = 0.021) and body mass index (BMI) > 35 (p = 0.003) were significantly associated with increased likelihood of postoperative complications following flap reconstruction in these patients. Additionally, fistulas due to cancer resections had a higher likelihood of postoperative complications compared with fistulas due to bowel disease or obstetric complications (p = 0.04). Conclusion Flap reconstruction can be successfully used for complex or refractory gastrointestinal-to-genitourinary fistulas. However, considerable complication and recurrence rates were found in this population. Patients with a BMI > 35 and a history of smoking were at greatest risk in this cohort of experiencing postoperative complications.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2GTzSUu

Intraoperative Perfusion Assessment in Mastectomy Skin Flaps: How Close are We to Preventing Complications?

J reconstr Microsurg
DOI: 10.1055/s-0039-1679958

Background: Mastectomy flap necrosis is the source of considerable morbidity and cost following breast reconstruction. A great deal of effort has been put forth to predicting and even preventing its incidence intraoperatively. Methods: A review of the literature was performed evaluating the evidence of mastectomy skin flap perfusion technologies. Results: Multiple technologies have leveraged spectroscopy and/or angiography to provide real-time assessment of flap perfusion, including indocyanine green, fluorescein, and light-based devices. Conclusion: This manuscript endeavors to review the evidence on mastectomy skin flap perfusion analysis, highlighting the benefits, and downsides of the current technologies and identifying exciting areas of future research and development.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2tyvH8Y

A relative risk assessment of the open burning of WEEE

Abstract

Waste electric and electronic equipment (WEEE) represents a potential secondary source of valuable materials, whose recovery is a growing business activity worldwide. In low-income countries, recycling is carried out under poorly controlled conditions resulting in severe environmental pollution. High concentrations of both metallic and organic pollutants have been confirmed in air, soil, water, and sediments in countries with informal recycling areas. The release of these contaminants into the environment presents a risk to the health of the exposed population that has been widely acknowledged but still needs to be quantified. The aim of this work was to evaluate the relative risk from inhalation associated with the open burning of different kinds of WEEE. The shrinking core model was applied to estimate the concentration of the metals which would be released into the environment during the incineration of different types of WEEE. In addition, the potential generation of dioxins during the same informal practice was estimated, based on the plastic content of the WEEE. The results provided for the first time a comparative analysis of the risk posed from the open burning of WEEE components, proposing a methodology to address the absolute risk assessment to workers from the informal recycling of WEEE.

https://ift.tt/2Ipvz5M

Enhanced adsorption of cationic Pb(II) and anionic Cr(VI) ions in aqueous solution by amino-modified nano-sized illite-smectite clay

Abstract

A raw illite-smectite mixed-layered clay (RI/S) was ground for preparing nano-sized I/S clay (NI/S) and subsequently amino-functionalized via grafting of 3-aminopropyltrithoxysilane (APTES) (NH₂-RI/S and NH₂-NI/S, respectively). The samples were characterized by particle size analysis, specific surface area measurement, X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and ²⁹Si nuclear magnetic resonance (²⁹Si NMR). Compared to RI/S, NI/S has a narrow particle size distribution and appears in a platelet-like morphology due to the disintegration/exfoliation of RI/S after grinding. Based on the ²⁹Si NMR spectra, the appearances of tri-silicate units indicate the chemically grafting of APTES molecules on NH₂-RI/S and NH₂-NI/S, respectively. NH₂-NI/S can adsorb greater amounts of Pb(II) cations and Cr(VI) anions rather than NH₂-RI/S since NH₂-NI/S grafts more amounts of amine groups (-NH₂). The isotherm data for adsorption of Pb(II) cations and Cr(VI) anions can be described by the Langmuir model at different temperatures (i.e., 10 °C, 30 °C, and 50 °C), respectively. The maximum adsorption amounts of Pb(II) cations and Cr(VI) anions onto NH₂-NI/S calculated by the Langmuir isotherm model are 131.23 mg/g and 36.91 mg/g at 50 °C, respectively. The adsorptions of Pb(II) cations and Cr(VI) anions onto NH₂-NI/S involve in the surface complexation of NI/S and amine groups.

https://ift.tt/2T7tcIV

Biosorption of glycerol impurities from biodiesel production onto electrospun chitosan-based nanofibers: equilibrium and thermodynamic evaluations

Abstract

The increase in biodiesel production has been leading to an excess amount of crude glycerol and, consequently, serious environmental issues. For this reason, electrospun chitosan-based nanofibers (CB-EN), composed by chitosan and poly(ethylene oxide) (PEO), were synthesized to apply in the biosorption of impurities from industrial glycerol. To evaluate the biosorption efficiency, the chitosan-based nanofiber was compared to other chitosan-based biosorbents (chitosan biopolymeric film and chitosan powder). The equilibrium and thermodynamic studies were successfully performed to comprehend the interaction mechanisms through the biosorption of glycerol pigments onto electrospun chitosan-based nanofibers. The temperature effect was evaluated by experimental equilibrium curves. Freundlich and BET models were used to estimate isotherm parameters. Gibbs free energy change, enthalpy change, entropy change, and isosteric heat of biosorption were quantified. The equilibrium curves showed that the highest equilibrium relative adsorption (340.7 g⁻¹) was reached at 60 °C. The BET model was the most suitable to represent the equilibrium behavior. The thermodynamic parameters indicated that the biosorption was spontaneous, exothermic, random, and energetic heterogeneous. Therefore, this work developed a green and efficient alternative to refine industrial glycerol.

Graphical abstract

Note: This data is mandatory. Please provide

https://ift.tt/2GWYOL6

Carious lesion activity assessment in clinical practice: a systematic review

Abstract

Objectives

The objective of the manuscript is to systematically review the different techniques developed for activity assessment of coronal carious lesions (AACCL) in clinical settings.

Materials and methods

A search of PubMed identified original articles in English reporting on the different concepts/tools for AACCL in clinical settings and, when available, data related to their in vivo/in situ validation in terms of sensitivity, specificity, inter- and intra-examiner reproducibilities, area under the receiving operating curve, positive predictive value, negative predictive value, and relative risk of lesion progression.

Results

The present review included 25 articles. Four groups of techniques are available (1) systems based on combinations of visual and tactile criteria; devices based on (2) pH assessment, (3) fluorescence, or (4) bioluminescence. The most studied systems are those based on combinations of visual and tactile parameters when bioluminescence suffers from the lack of in vivo evaluation. Validation studies showed a wide disparity among protocols in terms of populations, dentitions, teeth surfaces, study design, the gold standard, and validation criteria.

Conclusion

There is a need for definition and harmonization of standards for activity assessment-related concepts/tools, as well as further investigations for in vivo validation of newly developed tools.

Clinical relevance

Carious lesion activity is an important component to be taken into account when making decisions as to appropriate clinical caries management. The development and use of validated techniques which are easy to use in everyday dental practice are important.

https://ift.tt/2T9GYuC

Einfluss der prophylaktischen Ganzhirnbestrahlung auf das Gesamtüberleben von Patienten mit einem fortgeschrittenen nicht-kleinzelligen Bronchialkarzinom

https://ift.tt/2T3yHIR

Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non–Small Cell Lung Cancer

This phase 2 clinical trial examines the outcomes of patients with early-stage non–small cell lung cancer receiving neoadjuvant stereotactic ablative radiotherapy followed by surgery.

https://ift.tt/2SWVoPK

Association of Intake of Whole Grains and Dietary Fiber With Risk of Hepatocellular Carcinoma in US Adults

This cohort study evaluates the association of increased intake of whole grains and dietary fiber with the risk of hepatocellular carcinoma.

https://ift.tt/2E64uzo

Techniques and Thresholds for Quantifying Circulating Tumor Cells in Breast Cancer

To the Editor We read with great interest the article by Sparano et al, who evaluated the association of the presence of circulating tumor cells (CTCs) in a peripheral blood sample obtained approximately 5 years after diagnosis with late clinical recurrence of operable human epidermal growth factor receptor 2–negative breast cancer (BC). The authors concluded that a positive CTC assay result 5 years after diagnosis of estrogen receptor–positive BC provided independent prognostic information for late clinical recurrence. This impressive finding raises 2 important issues.

https://ift.tt/2SWVoiI

Nivolumab Plus Ipilimumab vs Sunitinib for Metastatic Renal Cell Carcinoma

This cost-effectiveness analysis compares nivolumab plus ipilimumab vs sunitinib to examine whether the drug combination is cost-effective from a US payer perspective as a first-line treatment for intermediate- and poor-risk patients with metastatic renal cell carcinoma.

https://ift.tt/2E64gZ4

Techniques and Thresholds for Quantifying Circulating Tumor Cells in Breast Cancer—In Reply

In Reply Liu and colleagues raised 2 important issues regarding our report on the use of a circulating tumor cell (CTC) assay as a prognostic biomarker for late recurrence in localized, estrogen receptor–positive, human epidermal growth factor receptor 2–negative breast cancer. First, they point out the potential limitations of the CTC assay used in our study, which detects only tumor cells expressing epithelial cell adhesion molecule (EpCAM) and thus does not detect other cell populations that may have greater potential to seed distant sites and contribute to the development of clinically evident metastases. There are more than 50 different CTC assays currently available; they vary in their methodology for detection and cell populations detected and hence vary in their sensitivity and specificity for CTC detection. In 1 of the few reports of a cross-platform comparison of 2 different CTC assays in patients with advanced prostate cancer, 1 assay that detected nonepithelial and epithelial populations exhibited greater clinical sensitivity, higher CTC cell counts, and more robust prognostic information than another assay that detected only an EpCAM-positive population. Additional studies are needed that involve cross-platform comparisons of assays that differ in their detection method and cell populations detected in breast cancer and other cancers.

https://ift.tt/2SQKKcZ

Multiple Cutaneous Nodules and Limb Swelling

A man in his 30s with painless swelling of the left upper limb and nodules on the left side of the chest and abdomen developed edema in the left upper limb 20 days after examination. What is your diagnosis?

https://ift.tt/2E641gC

Evaluating New Rules on Transparency in Cancer Research and Drug Development

This Viewpoint evaluates new transparency policies in cancer research and drug development.

https://ift.tt/2STFJQY

Elevated 1-h post-load plasma glucose is associated with right ventricular morphofunctional parameters in hypertensive patients

Abstract

Purpose

Emerging data demonstrate that type 2 diabetes mellitus (T2DM) is associated with right ventricular (RV) dysfunction. A cutoff point of 155 mg/dL for the 1-hour (h) post-load plasma glucose, during oral glucose tolerance test (OGTT), identifies patients with normal glucose tolerance (NGT) at high risk to develop T2DM and cardiovascular (CV) disease. We investigated if 1-h post-load glucose may affect RV geometry and function in a group of never-treated hypertensive individuals.

Methods

We enrolled 446 Caucasian newly diagnosed hypertensive outpatients. All patients underwent an OGTT and a standard echocardiography. The tricuspid annular plane systolic excursion (TAPSE) and the RV fractional area change (RVFAC) were measured together with systolic pulmonary arterial pressure (s-PAP) and pulmonary vascular resistances (PVR). Insulin sensitivity was evaluated using the Matsuda index.

Results

Among all partecipants, 296 had NGT, 100 impaired glucose tolerance (IGT), and 50 T2DM. Considering the cutoff point of 155 mg/dl for 1-h glucose, NGT subjects were stratified into two groups: NGT < 155 (n = 207), NGT ≥ 155 (n = 89). Subjects NGT ≥ 155 presented a worse metabolic and inflammatory profile than NGT < 155. RV functional parameters (TAPSE, RVFAC, TAPSE/s-PAP, and TAPSE/PVR) were significantly reduced in NGT ≥ 155 subjects compared with NGT < 155 patients. On the contrary, s-PAP and PVR were significantly higher. At multiple regression analysis, 1-h glucose was the strongest predictor of TAPSE in NGT ≥ 155, IGT, and T2DM.

Conclusions

The presence of RV impairment in hypertensive NGT ≥ 155 subjects further complicates their CV burden and it may, at least in part, justify the worse clinical outcome in this setting of patients.

https://ift.tt/2GRRO1Y

Beim HPV-assoziierten Oropharynxkarzinom ist die Radiochemotherapie mit Cisplatin der Bioradiotherapie mit Cetuximab in Bezug auf das Gesamtüberleben überlegen

https://ift.tt/2tt1VCu

Elevated 1-h post-load plasma glucose is associated with right ventricular morphofunctional parameters in hypertensive patients

Abstract

Purpose

Emerging data demonstrate that type 2 diabetes mellitus (T2DM) is associated with right ventricular (RV) dysfunction. A cutoff point of 155 mg/dL for the 1-hour (h) post-load plasma glucose, during oral glucose tolerance test (OGTT), identifies patients with normal glucose tolerance (NGT) at high risk to develop T2DM and cardiovascular (CV) disease. We investigated if 1-h post-load glucose may affect RV geometry and function in a group of never-treated hypertensive individuals.

Methods

We enrolled 446 Caucasian newly diagnosed hypertensive outpatients. All patients underwent an OGTT and a standard echocardiography. The tricuspid annular plane systolic excursion (TAPSE) and the RV fractional area change (RVFAC) were measured together with systolic pulmonary arterial pressure (s-PAP) and pulmonary vascular resistances (PVR). Insulin sensitivity was evaluated using the Matsuda index.

Results

Among all partecipants, 296 had NGT, 100 impaired glucose tolerance (IGT), and 50 T2DM. Considering the cutoff point of 155 mg/dl for 1-h glucose, NGT subjects were stratified into two groups: NGT < 155 (n = 207), NGT ≥ 155 (n = 89). Subjects NGT ≥ 155 presented a worse metabolic and inflammatory profile than NGT < 155. RV functional parameters (TAPSE, RVFAC, TAPSE/s-PAP, and TAPSE/PVR) were significantly reduced in NGT ≥ 155 subjects compared with NGT < 155 patients. On the contrary, s-PAP and PVR were significantly higher. At multiple regression analysis, 1-h glucose was the strongest predictor of TAPSE in NGT ≥ 155, IGT, and T2DM.

Conclusions

The presence of RV impairment in hypertensive NGT ≥ 155 subjects further complicates their CV burden and it may, at least in part, justify the worse clinical outcome in this setting of patients.

https://ift.tt/2GRRO1Y

A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors

Conditions:   Melanoma;   Cervical Carcinoma;   Pancreatic Carcinoma;   Triple Negative Breast Cancer;   Hepatocellular Carcinoma;   Urothelial Carcinoma;   Squamous Cell Carcinoma of the Head and Neck;   Nasopharyngeal Carcinoma;   Renal Cell Carcinoma;   Colorectal Carcinoma;   Endometrial Carcinoma;   Non-small Cell Lung Carcinoma;   Small Cell Lung Carcinoma;   Gastric or Gastroesophageal Junction Adenocarcinoma;   Advanced or Metastatic Solid Tumors
Interventions:   Biological: XmAb®22841;   Biological: Pembrolizumab (Keytruda®)
Sponsors:   Xencor, Inc.;   ICON plc
Not yet recruiting

https://ift.tt/2tyouFQ

Multiparametric Magnetic Resonance Imaging Versus Fine Needle Aspiration Cytology for Parotid Gland Neoplasms

Conditions:   Parotid Neoplasm;   Parotid Cancer
Interventions:   Diagnostic Test: Multiparametric Magnetic Resonance Imaging;   Diagnostic Test: Fine Needle Aspiration Cytology;   Diagnostic Test: Clinical Evaluation;   Diagnostic Test: Final Histopathological Diagnosis
Sponsor:   Davide Di Santo
Recruiting

https://ift.tt/2H1OIbV

Observations, knowledge, and attitude towards treatment options in patients with dry mouth: a survey among German dentists

Abstract

Objectives

The aim of this study was to investigate the attitude, observations, and knowledge of German dentists regarding the management of dry mouth.

Materials and methods

A questionnaire including queries about attitudes, observations, and treatment options in patients with dry mouth was developed and sent to all 1251 dentist members of a regional German dental association.

Results

An overall total of 284 returned questionnaires were included in the analyses, which relates to a response rate of 22.7%. Dentists infrequently encountered dry mouth in their clinical routine, yet were well aware that patients suffer from the symptoms of dry mouth; for affected patients, the majority of participating dentists provided specific dental prophylaxis measures. Drug side effects, neoplasia, and psychological disorders were regarded as the primary etiological factors for dry mouth, and caries, increased plaque formation, and rhagades as the most frequently observed clinical symptoms. While the majority of participating dentists was of the opinion that saliva substitutes are useful treatment options in patients with dry mouth, only few frequently recommended their use. Mechanical and gustatory stimulation of salivary flow as well as the advice to rinse with water were the most frequently pursued treatment options.

Conclusions

Despite the high prevalence of dry mouth identified in epidemiological studies, it appears to be an infrequent observation in clinical routine.

Clinical relevance

Pre- and postgraduate education should sensitize dentists for dry mouth and its treatment options.

https://ift.tt/2txlU2U

Pneumocephalus and pneumoventricle

CASE REPORT

Year : 2019  |  Volume : 14  |  Issue : 1  |  Page : 325-328

Delayed pneumoventricle following endonasal cerebrospinal fluid rhinorrhea repair with thecoperitoneal shunt

Shyam Sundar Krishnan, Adarsh Manuel, Madabhushi Chakravarthy Vasudevan
Department of Neurosurgery, Achanta Lakshmipathi Neurosurgical Centre, Voluntary Health Services Hospital, Chennai, Tamil Nadu, India

Date of Web Publication

21-Feb-2019

Correspondence Address:
Dr. Shyam Sundar Krishnan
Department of Neurosurgery, Achantha Lakshmipathy Neurosurgical Centre, Voluntary Health Services, TTTI Post, Taramani, Chennai - 600 113, Tamil Nadu 
India

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/ajns.AJNS_224_18

Abstract

Pneumocephalus and pneumoventricle are well-documented in neurosurgical practice. Although both are common posttraumatic sequelae, iatrogenic causes are also well recognized. Iatrogenic causes may be seen after intracranial surgical procedures or cerebrospinal fluid (CSF) diversion procedures. Small amount of pneumoventricle postshunt procedure is usually a self-limiting condition. Rarely, the patient may develop tension pneumoventricle which requires emergency intervention. The occurrence of delayed tension pneumoventricle/pneumatocele following surgery for CSF rhinorrhea with CSF diversion procedures is very rare. We report one case of late presentation of delayed tension pneumoventricle with temporal pneumatocele in a patient who underwent transnasal endoscopic repair of CSF fistula followed by thecoperitoneal shunt. This condition is potentially lethal that requires prompt recognition and surgical treatment.

Keywords: Cerebrospinal fluid rhinorrhea, pneumatocele, pneumocephalus, tension pneumoventricle, thecoperitoneal shunt

How to cite this article: Krishnan SS, Manuel A, Vasudevan MC. Delayed pneumoventricle following endonasal cerebrospinal fluid rhinorrhea repair with thecoperitoneal shunt. Asian J Neurosurg 2019;14:325-8

How to cite this URL: Krishnan SS, Manuel A, Vasudevan MC. Delayed pneumoventricle following endonasal cerebrospinal fluid rhinorrhea repair with thecoperitoneal shunt. Asian J Neurosurg [serial online] 2019 [cited 2019 Feb 21];14:325-8. Available from: http://www.asianjns.org/text.asp?2019/14/1/325/250010

Introduction

The occurrence of pneumoventricle as a delayed complication of cerebrospinal fluid (CSF), rhinorrhea repair with thecoperitoneal shunt is a rare presentation. Tension pneumocephalus is a known and common entity as compared to tension pneumoventricle. The presence of pneumatocele in the temporal lobe in association with the above condition makes it a unique clinical presentation.

Case Report

This 48-year-old female presented with complaints of CSF rhinorrhea since 2 months. There was no history or clinical finding suggestive of trauma or meningitis. Her neurological examination otherwise was unremarkable. Computed tomography (CT) face/skull base followed by magnetic resonance imaging (MRI) brain and diagnostic nasal endoscopy were done which showed the defect in the cribriform plate and left a lateral wall of the sphenoid sinus [Figure 1]. Lumbar puncture done showed the CSF opening pressure of 35 cm of water and no evidence of infection.

Figure 1: Magnetic resonance images of the patient showing cerebrospinal fluid fistula in cribriform plate (short arrow) and lateral wall of sphenoid sinus (long arrow) and computed tomography paranasal sinuses bone window showing defect (long arrow) in the sphenoid bone with cerebrospinal fluid filling into the left sphenoid sinus (long arrow) Click here to view

She underwent transnasal endoscopic repair of CSF fistula along with placement of thecoperitoneal shunt with no anti-siphon device. The bath-plug technique was used to seal the defects by introducing a fat plug with a specifically secured vicryl suture into the intradural space, followed by applying traction on the suture to seal the defect much like a bathplug seals a bath. Rectus abdominis fascia graft was harvested from the same abdominal wound used for shunt placement. The defect was further reinforced by fascia, fat and surgical, and fibrin sealant. It was decided to place thecoperitoneal shunt as the CSF opening pressure was very high to prevent the recurrent CSF leak. Postoperatively, she was symptom-free and discharged to home.

After 1 month, she presented with memory disturbances, multiple episodes of vomiting and headache. There was no recurrence of CSF rhinorrhea or postnasal drip. MRI brain showed pneumoventricle with right temporal pneumatocele [Figure 2]. Diagnostic endoscopy was done which showed dislodged fascia graft. She underwent emergency repacking of the CSF fistula with the removal of thecoperitoneal shunt and aspiration of pneumoventricle underwater seal which was under high pressure. Fasica graft was repositioned to cover the defect after sealing it with fat using the bath-plug technique as in the previous surgery. Fat and fascia packing was reinforced with a pedicled Hadad flap and fibrin sealant. She improved in her symptoms postoperatively. Postoperative CT brain showed good resolution of pneumoventricle with reduced size of ventricular system [Figure 3]. She remained symptom free at 6-month follow-up.

Figure 2: Magnetic resonance imaging brain showing pneumatocele (long arrow) in the right temporal lobe and pneumoventricle (short arrow) Click here to view

Figure 3: Postoperative computed tomography brain showing good resolution of tension pneumoventricle and right temporal pneumatocele Click here to view

Discussion

Pneumocephalus is defined as the presence of air in the intracranial compartment due to communication between intracranial and extracranial compartments.^[1],[2],[3] Tension pneumocephalus is a rarer form of pneumocephalus in which the air is under high pressure.^{[1],[2],[4],[5],[6],[7]}Pneumocephalus occur most commonly in head injuries.^[1],[2],[3] Intra- and post-operative pneumocephalus/pneumoventricle is well-documented, especially, in sitting position surgeries, nitrous oxide anesthesia, and CSF diversion surgeries.^[1],[2],[3] Other conditions causing pneumocephalus are CNS infections caused by gas-producing organisms, congenital neurenteric cysts, and postradiotherapy for nasopharyngeal carcinoma.^{[1],[2],[4],[5],[6],[7]} Small amounts of pneumoventricle alone are common after shunt surgeries, ventricular tumor surgeries.^{[1],[2],[3],[8]} Sometimes, wound breakdown following the shunt surgeries may cause influx of air peritubally and cause pneumoventricle.^[9] Delayed tension pneumoventricle is an extremely rare complication and <50 cases have been described in the literature.^[1]Pneumocephalus/pneumoventricle is usually benign which does not require any treatment, and it decreases at a rate of 25% per week.^{[4],[9],[10],[11],[12]}

Two different mechanisms have been proposed in the development of delayed tension pneumoventricle/pneumocephalus.^{[1],[2],[3],[13],[14]}

1. Dandy's theory of ball valve mechanism: one-way ball valve mechanism causing air to flow into the skull through dural defect where the exit is prevented by brain or meninges sealing the leak site
2. Horowitz inverted soda-bottle effect: negative pressure develops inside the cranial cavity as a result of excessive loss of CSF. This drop in intracranial pressure (ICP) causes air to flow from the extra to the intracranial space across the pressure gradient.

In our case, the patient presented with spontaneous CSF rhinorrhea and was treated by endoscopic skull base defect repair with thecoperitoneal shunt placement. CSF rhinorrhea can be due to traumatic or nontraumatic causes. Traumatic can be either due to head injuries causing skull base fractures or due to iatrogenic causes. Spontaneous leaks could be associated with or without raised ICP. High-pressure leaks could account up to 45% of the nontraumatic CSF rhinorrhea.^[15] Sustained increase in ICP causes bony erosion and creation of an osteodural defect in pneumatized parts of the skull base such as cribriform plate, craniopharyngeal canal, sella, and spheno-occipital synchondrosis leading to CSF leak.^[7],[15] CSF leaks in these cases have been postulated to represent a manifestation of benign intracranial hypertension or pseudotumor cerebri.^{[16],[17],[18],[19]} In our case also CSF leak was associated with raised ICP with no evidence of trauma or infection. This could be an underlying benign ICP with or without congenital defect.

Normal pressure leaks represent 55% of the nontraumatic cases of the CSF rhinorrhea.^[20],[21] It is hypothesized that the spontaneous leak is due to point erosions in the skull base which occur in normal person as a result of physiologic alterations in CSF pressure with transient increase in ICP up to 80 mm of water lasting for few seconds.^[15] Other nontraumatic causes of CSF leak include congenital skull base defects, erosion of the skull base by tumors, infection, mucocele, and following radiation.

CSF diversion in patients with long-standing raised ICP may result in the pneumoventricle by air aspiration through a preexisting congenital or iatrogenic skull base erosion/fistula.^[3] These fistulous sites/erosion points are plugged by scarred meninges or gliotic brain which open up due to a drop in ICP causing inward flow of air. This air is prevented from escaping by temporarily resealing of meningeal cicatrix and this cycle repeatedly happens, resulting in tension pneumoventricle (ball valve mechanism). Shunts by their siphon effect can create significant negative ICP drop which ranges from −30 to −155 mm of water, and sometimes as low as −440 mm of water.^[2],[5] Pneumatocele is located close to the site of fistulae and more common in the temporal lobe. In our case also there might have been a sustained negative pressure caused by the thecoperitoneal shunt without anti-siphon device.

Pneumoventricle presents usually with symptoms and signs of raised ICP such as a recurrent headache with vomiting, impairment of consciousness, seizures, memory disturbances, and gait disturbance. Sometimes, patients present with acute or chronic meningitis. Intracranial splashing sounds called "bruit hydroaerique" are characteristic in some patients. Similarly, our patient also presented with memory disturbances and cognitive impairment during the second presentation.

The delay from CSF shunting to the development of pneumocephalus may vary from a week up to 5 years.^[7],[22] The usage of high-pressure shunts and antisiphon devices have been recommended by some authors to prevent this complication.^[1],[2],[23] Our routine policy is to place Chhabra standard adult thecoperitoneal shunt with no anti-siphon device. However, anti-siphon device has advantages of preventing over-drainage of CSF, and the reservoir gives access to check the patency of the shunt system. We have seen an increased risk of shunt obstruction with anti-siphon device. We had 42 cases who underwent Lumbar-peritoneal (LP) shunts without anti-siphon device in the past 5 years and none of them presented with shunt obstruction or shunt-related morbidity other than shunt migration (five patients) and abdominal pseudocyst (two patients). Programmable shunt provides the benefit of adjusting the pressure setting according to the ventricular pressure. We routinely do not use programmable LP shunts as ours is a resource-limited center with most of the patients coming from low-socioeconomic strata.

Prevention of infection, treatment of raised ICP, aspiration of pneumoventricle, closure of fistula, and removal of shunt tube are the keys to successful management of tension pneumoventricle secondary to CSF fistula.^[23] Broad-spectrum antibiotics are used after shunt removal, but its prophylactic usage is debated.^[1],[5],[23] Removal of the shunt tube relieves the sustained negative pressure which may cause recurrent pneumoventricle/pneumocephalus. Postshunt removal a temporary CSF diversion is preferred by some authors, especially, if the infection is doubted clinically or confirmed.^[1],[2],[23]

In our case, as there was dislodgement of fat-fascia graft, repacking was done followed by aspiration of pneumoventricle underwater seal and thecoperitoneal shunt was removed. We feel the tension pneumoventricle caused air to dissect into the right temporal lobe region under pressure forming the temporal pneumatocele. The shunt was removed to alleviate negative pressure gradient as it was nonprogrammable shunt with no anti-siphon device. The patient had complete resolution of symptoms after the procedure. This makes us think that we should probably reconsider the usage of anti-siphon device and also a pedicled flap to repair the skull base defects. A programmable valve may be the best choice in financially affordable patients. In patients with normal/moderately high ICP (25 cm of water), a temporary lumbar drain can be considered for few days until the defects heal thus preventing the recurrent CSF leaks.

Conclusion

Although it is a rare entity, tension pneumoventricle should be considered in patients who have undergone CSF diversion procedures along with anterior skull base repair. Sometimes, it can occur as a delayed complication which may lead to acute neurological deterioration and sudden death. Hence, prompt diagnosis is necessary for timely intervention and prevention.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 

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Figures

  [Figure 1], [Figure 2], [Figure 3]