bluuebunny/crossref_metadata_2025 huggingface dataset:
Attitudes, practices, and priority of HIV screening and testing among clinical providers in Transylvania and Moldavia, Romania
Authors: Barbosu Cabiria M. , Radulescu Amanda , Manciuc Carmen , Muir Erin , Levandowski Brooke A. , Dye Timothy
Published: December 2019

Screening and linkage to care are core, foundational strategies for HIV transmission prevention and for identifying People Living with HIV (PLHIV). In Romania – with an atypical experience in the HIV/AIDS epidemic – providing care for HIV+ patients identified early is a priority, though screening and testing can pose a challenge in some areas.

Methods

A survey of 125 clinical providers to explore important dimensions of HIV/ AIDS clinical care was conducted in Transylvania and Moldavia, where clinicians identified poor/ latent screening as a major problem in providing timely care and in preventing the spread of disease. We analyzed determinants of offering HIV screening/testing to patients using Pearson Chi-square analysis and logistic regression. Logistic regression generated Odds Ratios (OR) to reflect the magnitude of association between the relevant variables, with 95% confidence interval (95% CI) indicating statistical range.

Results

In total, 40.8% of providers did not provide HIV screening/testing to at least one segment of the population. Hospital-based providers were significantly more likely to offer HIV screening/testing to all segments than were non-hospital-based providers (58.1% v. 35.5%, respectively; p < .05). Providers located within institutions with screening/testing policies were more likely to offer such services to their patients (p < .05). Overall, 94.4% of providers indicated interest in more training around HIV screening/testing.

Discussion

Reaching Romanian and global goals for reducing HIV require more timely screening and action based on positive status. Romanian clinicians are interested in expanding HIV screening/testing and are interested in participating in training that helps them feel more prepared to undertake this work.
Availability of emergency obstetric and newborn care services at public health facilities of Sindh province in Pakistan
Authors: Kumar Ramesh , Ahmed Jamil , Anwar Fozia , Somrongthong Ratana
Published: December 2019

Background

Basic and comprehensive emergency obstetric care services in Pakistan remain a challenge considering continued high burden of maternal and newborn mortality. This study aimed to assess the availability of emergency obstetric and newborn care in Sindh Province of Pakistan.

Methods

This cross-sectional survey was conducted in twelve districts of the Sindh province in Pakistan. The districts were selected based on the maternal neonatal and child health indicators. Data were collected from 63 public-sector health facilities including district, Taluka (subdistrict) headquarters hospitals and rural health centers. Basic and comprehensive emergency obstetric newborn care services were assessed through direct observations and interviews with the heads of the health facilities by using a World Health Organization pretested and validated data collection tool. Participants interviewed in this study included the managers and auxiliary staff and in health facilities.

Results

Availability of caesarean section (23, 95% C.I. 14.0–35.0) and blood transfusion services (57, 95% CI. 44.0–68.0), the two components of comprehensive emergency obstetric and newborn care, was poor in our study. However, assessment of the seven components of basic emergency obstetric and newborn services showed that 92% of the health facilities (95% C.I. 88.0–96.0) had parenteral antibiotics, 90%, (95% C.I. 80.0–95.0) had oxytocin, 92% (95% CI 88.0–96.0) had manual removal of the placenta service, 87% (95%, C.I. 76.0–93.0) of the facilities had staff who could remove retained products of conception, 82% (95% C.I. 71.0–89.0) had facilities for normal birth and 80% (95% C.I. 69.0–88.0) reported presence of neonatal resuscitation service.

Conclusion

Though the basic obstetric and newborn services were reasonably available, comprehensive obstetric and newborn services were not available as per the World Health Organization’s standards in the surveyed public health facilities. Ensuring the availability of caesarean section and blood transfusion services within these facilities may improve population’s access to these essential services around birth.
Systematic analysis of gene expression profiles reveals prognostic stratification and underlying mechanisms for muscle-invasive bladder cancer
Authors: Zhang Ping-Bao , Huang Zi-Li , Xu Yong-Hua , Huang Jin , Huang Xin-Yu , Huang Xiu-Yan
Published: December 2019

Background

Muscle-invasive bladder cancer (MIBC) is originated in the muscle wall of the bladder, and is the ninth most common malignancy worldwide. However, there are no reliable, accurate and robust gene signatures for MIBC prognosis prediction, which is of the importance in assisting oncologists to make a more accurate evaluation in clinical practice.

Methods

This study used univariable and multivariable Cox regression models to select gene signatures and build risk prediction model, respectively. The t-test and fold change methods were used to perform the differential expression analysis. The hypergeometric test was used to test the enrichment of the differentially expressed genes in GO terms or KEGG pathways.

Results

In the present study, we identified three prognostic genes, KLK6, TNS1, and TRIM56, as the best subset of genes for muscle-invasive bladder cancer (MIBC) risk prediction. The validation of this stratification method on two datasets demonstrated that the stratified patients exhibited significant difference in overall survival, and our stratification was superior to three other stratifications. Consistently, the high-risk group exhibited worse prognosis than low-risk group in samples with and without lymph node metastasis, distant metastasis, and radiation treatment. Moreover, the upregulated genes in high-risk MIBC were significantly enriched in several cancer-related pathways. Notably, PDGFRB, a receptor for platelet-derived growth factor of PI3K-Akt signaling pathway, and TUBA1A were identified as two targets of multiple drugs. In addition, the angiogenesis-related genes, as well as two marker genes of M2 macrophage, CD163 and MRC1, were highly upregulated in high-risk MIBC.

Conclusions

In summary, this study investigated the underlying molecular mechanism and potential therapeutic targets associated with worse prognosis of high-risk MIBC, which could improve our understanding of progression of MIBC and provide new therapeutic strategies for the MIBC patients.
Sevoflurane inhibits the progression of ovarian cancer through down-regulating stanniocalcin 1 (STC1)
Authors: Zhang Chuanfeng , Wang Baosheng , Wang Xiuqin , Sheng Xiugui , Cui Yongchun
Published: December 2019

Background

Ovarian cancer is one of the leading causes of female death worldwide, with a poor prognosis of advanced patients. Sevoflurane, a volatile anesthetic commonly used in clinical operations, has been reported to have anti-cancer activity against some tumors. In the present study, we aimed to investigate the effects of sevoflurane on the progression of ovarian cancer and its potential mechanism.

Methods

The effects of sevoflurane on ovarian cancer cell viability, proliferation, migration, invasion, cell cycle, and apoptosis were determined by functional experiments in vitro. Gelatin zymography assay was performed to examine MMP9 activity. In vivo, sevoflurane was injected into mice of transplantation tumor with SKOV3 cells or with pcDNA-STC1 treated SKOV3 cells.

Results

We found that sevoflurane inhibited the viability of SKOV3 and OVCAR3 cells in a dose-dependent manner, and colony formation assay revealed that sevoflurane inhibited ovarian cancer cell colony-formation abilities. Additionally, sevoflurane could induce cell cycle arrest and promote cell apoptosis in SKOV3 and OVCAR3 cells. Moreover, sevoflurane reduced the migration and invasion abilities of SKOV3 and OVCAR3 cells, as well as the MMP-9 activity. Furthermore, sevoflurane down-regulated the expression of stanniocalcin 1 (STC1), and up-regulation of STC1 could reverse the inhibitory effects of sevoflurane on cell proliferation and invasion. In vivo, sevoflurane significantly inhibited the tumor growth, which was be reversed by STC1 overexpression.

Conclusion

These data reveal an anti-cancer activity of sevoflurane on the growth and invasion of ovarian cancer, which may be through down-regulating STC1. Sevoflurane may serve as a potential anti-cancer agent in ovarian cancer therapy.
Protection induced by malaria virus-like particles containing codon-optimized AMA-1 of Plasmodium berghei
Authors: Lee Dong-Hun , Chu Ki-Back , Kang Hae-Ji , Lee Su-Hwa , Chopra Manika , Choi Hyo-Jick , Moon Eun-Kyung , Inn Kyung-Soo , Quan Fu-Shi
Published: December 2019

Background

Despite the extensive endeavours, developing an effective malaria vaccine remains as a great challenge. Apical membrane antigen 1 (AMA-1) located on the merozoite surface of parasites belonging to the genusPlasmodiumis involved in red blood cell invasion.

Methods

Influenza virus-like particle (VLP) vaccines containing codon-optimized or native (non-codon optimized) AMA-1 fromPlasmodium bergheiwere generated. VLP-induced protective immunity was evaluated in a mouse model.

Results

Mice immunized with VLP vaccine containing the codon-optimized AMA-1 elicited higher levels ofP. berghei-specific IgG and IgG2a antibody responses compared to VLPs containing non-codon optimized AMA-1 before and after challenge infection. Codon-optimized AMA-1 VLP vaccination induced higher levels of CD4+T cells, CD8+T cells, B cells, and germinal centre cell responses compared to non-codon optimized AMA-1 VLPs. Importantly, the codon-optimized AMA-1 VLP vaccination showed lower body weight loss, longer survival and a significant decrease in parasitaemia compared to non-codon optimized VLP vaccination.

Conclusion

Overall, VLP vaccine expressing codon-optimized AMA-1 induced better protective efficacy than VLPs expressing the non-codon optimized AMA-1. Current findings highlight the importance of codon-optimization for vaccine use and its potential involvement in future malaria vaccine design strategies.
Defining the larval habitat: abiotic and biotic parameters associated with Anopheles farauti productivity
Authors: McLaughlin Kimberley , Burkot Thomas R. , Oscar Jance , Beebe Nigel W. , Russell Tanya L.
Published: December 2019

Background

In the Solomon Island, the dominant malaria vector, Anopheles farauti, is highly anthropophagic and increasingly exophilic and early biting. While long-lasting insecticide-treated nets remain effective against An. farauti, supplemental vector control strategies will be needed to achieve malaria elimination. Presently, the only World Health Organization recommended supplemental vector control strategy is larval source management (LSM). Effective targeted larval source management requires understanding the associations between abiotic, chemical and biological parameters of larval habitats with the presence or density of vector larvae.

Methods

Potential and actual An. farauti larval habitats were characterized for presence and density of larvae and associated abiotic, chemical and biological parameters.

Results

A third of all sampled potential habitats harboured An. farauti larvae with 80% of An. farauti positive habitats being in three habitat classifications (swamps/lagoons, transient pools and man-made holes). Large swamps were the most abundant positive habitats surveyed (43% of all An. farauti positive habitats). Habitats with An. farauti larvae were significantly associated with abiotic (pH, nitrate, ammonia and phosphate concentrations and elevated temperature) and biotic (predators) parameters.

Conclusion

Large swamps and lagoons are the largest and most abundant An. farauti habitats in the Solomon Islands. Positive habitats were more frequently associated with the presence of predators (vertebrates and invertebrates) and higher water temperatures. Cohabitation with predators is indicative of a complex habitat ecosystem and raises questions about the potential of biological control as an effective control strategy. Increased presence of An. farauti with higher water temperature suggests a potential explanation for the coastal distribution of this species which is not found inland at elevated altitudes where temperatures would be cooler.
How far is the journey before malaria is knocked out of Zimbabwe? (or Africa): a commentary
Authors: Shiff Clive
Published: December 2019

Recent publications and statements have drawn attention to a sustainable system of managing malaria control interventions globally but especially on the Continent of Africa. Arbitrary and unstable governments often interfere with health programmes, causing upsurges in malaria transmission as well as other health issues. A well-run health infrastructure will deal with public health as a whole. This commentary follows historical conditions in Zimbabwe where much original work on malaria control was initiated and implemented and where unstable conditions happened through local politics. These periodic conditions of instability on the ground challenge the current philosophical thrust to eradication and stress the need and role of an established and well-staffed health infrastructure in each country. Such facilities should be well staffed and supplied with drugs and point-of care diagnostic tests to manage malaria and should be sustained to serve the community even after tools that can eradicate malaria are developed.
Producing routine malaria data: an exploration of the micro-practices and processes shaping routine malaria data quality in frontline health facilities in Kenya
Authors: Okello George , Molyneux Sassy , Zakayo Scholastica , Gerrets Rene , Jones Caroline
Published: December 2019

Background

Routine health information systems can provide near real-time data for malaria programme management, monitoring and evaluation, and surveillance. There are widespread concerns about the quality of the malaria data generated through routine information systems in many low-income countries. However, there has been little careful examination of micro-level practices of data collection which are central to the production of routine malaria data.

Methods

Drawing on fieldwork conducted in two malaria endemic sub-counties in Kenya, this study examined the processes and practices that shape routine malaria data generation at frontline health facilities. The study employed ethnographic methods—including observations, records review, and interviews—over 18-months in four frontline health facilities and two sub-county health records offices. Data were analysed using a thematic analysis approach.

Results

Malaria data generation was influenced by a range of factors including human resource shortages, tool design, and stock-out of data collection tools. Most of the challenges encountered by health workers in routine malaria data generation had their roots in wider system issues and at the national level where the framing of indicators and development of data collection tools takes place. In response to these challenges, health workers adopted various coping mechanisms such as informal task shifting and use of improvised tools. While these initiatives sustained the data collection process, they also had considerable implications for the data recorded and led to discrepancies in data that were recorded in primary registers. These discrepancies were concealed in aggregated monthly reports that were subsequently entered into the District Health Information Software 2.

Conclusion

Challenges to routine malaria data generation at frontline health facilities are not malaria or health information systems specific; they reflect wider health system weaknesses. Any interventions seeking to improve routine malaria data generation must look beyond just malaria or health information system initiatives and include consideration of the broader contextual factors that shape malaria data generation.
HDL-C to hsCRP ratio is associated with left ventricular diastolic function in absence of significant coronary atherosclerosis
Authors: Sun Lufan , Liu Xiaorui , Li Wenna , Jia Dalin
Published: December 2019

Background

High-density lipoprotein cholesterol (HDL-C) is considered as a protective marker of coronary atherosclerotic disease (CAD). It is still not clear if HDL-C is associated with left ventricular (LV) diastolic function in an inflammation-related manner in absence of significant coronary atherosclerosis.

Methods

392 patients who complained of chest pain and were suspected of CAD without heart failure were enrolled in this study. Coronary angiography or coronary artery CT scan was performed to detect coronary atherosclerosis. Transthoracic echocardiography was performed to evaluate cardiac function. Plasma level of HDL-C and high-sensitive C-reactive protein (hsCRP) were determined in each subject. Relationship between HDL-C/hsCRP ratio and LV diastolic function in subjects without significant coronary atherosclerosis was investigated.

Results

204 subjects without significant coronary plaques were analyzed finally, including 84 males and 120 females whose ages ranged from 30 to 84 years old. When divided into HDL-C/hsCRP quartiles, those in the fourth quartile demonstrated the best diastolic function (E/e’ 10.14 ± 2.87, P = 0.02 ). HDL-C/hsCRP was the most significant factor correlated with E/e’ in univariate regression analysis (r = − 0.232, P < 0.001) and multiple regression analysis adjusted by other factors (standardized β = − 0.258 , P < 0.0005 ). In logistic regression, HDL-C/hsCRP was proved to be a protective factor of LV diastolic dysfunction E/e’ > 14 (OR = 0.649, 95%CI 0.444–0.948,P = 0.025 ). The sensitivity and specificity of using HDL-C/hsCRP < 0.98 to predict LV diastolic dysfunction were 64.3% and 56.2%, respectively. HDL-C/hsCRP ratio presented a reduced trend as increasing rate of CV risk factors.

Conclusions

HDL-C/hsCRP ratio strongly correlates with LV diastolic function in absence of significant coronary atherosclerosis. Low HDL-C/hsCRP ratio tends to relate with LV diastolic dysfunction.
Issues on peritoneal metastasis of gastric cancer: an update
Authors: Wang Zhen , Chen Jun-qiang , Liu Jin-lu , Tian Lei
Published: December 2019

Background

Peritoneal metastasis (PM) is one of the most common forms of metastasis with a very poor prognosis in patients with gastric cancer (GC). The mechanisms, diagnosis, and management of PM remain controversial.

Main body

Stephen Paget’s “seed-and-soil” hypothesis gives us an illustration of the mechanisms of PM. Recently, hematogenous metastasis and exosomes from GC are identified as novel mechanisms for PM. Diagnostic accuracy of conventional imaging modalities for PM is not satisfactory, but texture analysis may be a useful adjunct for the prediction of PM. Biological markers in peritoneal washings are helpful in identifying patients at high risk of PM, but many limitations remain to be overcome. Response of PM from systemic chemotherapy alone is very limited. However, conversion therapy is confirmed to be safe and able to prolong the survival of GC patients with PM. As an important part of conversion therapy, intraperitoneal chemotherapy with taxanes has become an ideal approach with several advantages. Additionally, gastrectomy should be considered in patients who would tolerate surgery if a remarkable response to chemotherapy was observed.

Conclusion

Texture analysis is a reliable adjunct for the prediction of PM, and conversion therapy provides a new choice for GC patients with PM. The underlying mechanisms and new biological markers for GC patients with PM should be the direction of future studies. Furthermore, significant aspects of conversion therapy, such as timing and method of the operation, and the indications remain to be clarified.
Predictive value of serum procalcitonin for both initial and repeated immunoglobulin resistance in Kawasaki disease: a prospective cohort study
Authors: Shao Shuran , Luo Chunyan , Zhou Kaiyu , Hua Yimin , Wu Mei , Liu Lei , Liu Xiaoliang , Wang Chuan
Published: December 2019

Background

Intravenous immunoglobulin (IVIG) resistance prediction is one pivotal topic of interests in Kawasaki disease (KD) since those patients with KD resistant to IVIG might improve of an early-intensified therapy. Data regarding predictive value of procalcitonin (PCT) for IVIG resistance, particularly for repeated IVIG resistance in KD was limited. This study aimed to testify the predictive validity of PCT for both initial and repeated IVIG resistance in KD.

Methods

A total of 530 KD patients were prospectively recruited between January 2015 and March 2019. The clinical and laboratory data were compared between IVIG-responsive and IVIG-resistant groups. Multivariate logistic regression analysis was applied to determine the association between PCT and IVIG resistance. Receiver operating characteristic (ROC) curves analysis was further performed to assess the validity of PCT in predicting both initial and repeated IVIG resistance.

Results

The serum PCT level was significantly higher in initial IVIG-resistance group compared with IVIG-response group (p = 0.009), as well as between repeated IVIG responders and nonresponders (p = 0.017). The best PCT cutoff value for initial and repeated IVIG resistance prediction was 1.48 ng/ml and 2.88 ng/ml, respectively. The corresponding sensitivity was 53.9 and 51.4%, while the specificity were 71.8 and 73.2%, respectively. Multivariate logistic regression analysis failed to identify serum PCT level as an independent predictive factor for both initial and repeated IVIG resistance in KD.

Conclusions

Serum PCT levels were significantly higher in IVIG nonresponders, but PCT may not be suitable as a single marker to accurately predict both initial and repeated IVIG resistance in KD.
Oral health and plaque microbial profile in juvenile idiopathic arthritis
Authors: Grevich Sriharsha , Lee Peggy , Leroux Brian , Ringold Sarah , Darveau Richard , Henstorf Gretchen , Berg Joel , Kim Amy , Velan Elizabeth , Kelly Joseph , Baltuck Camille , Reeves Anne , Leahey Hannah , Hager Kyle , Brittnacher Mitchell , Hayden Hillary , Miller Samuel , McLean Jeffrey , Stevens Anne
Published: December 2019

Background

The oral microbiota has been implicated in the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. This study tested for associations between oral health, microbial communities and juvenile idiopathic arthritis (JIA).

Methods

A cross-sectional exploratory study of subjects aged 10–18 years with oligoarticular, extended oligoarticular and polyarticular JIA was conducted. Control groups included pediatric dental clinic patients and healthy volunteers. The primary aim was to test for an association between dental health indices and JIA; the secondary aim was to characterize the microbial profile of supragingival plaque using 16S rRNA gene sequencing.

Results

The study included 85 patients with JIA, 62 dental patients and 11 healthy child controls. JIA patients overall had significantly more gingival inflammation compared to dental patients, as evidenced by bleeding on probing of the gingiva, the most specific sign of active inflammation (p = 0.02). Overall, however, there was a trend towards better dental hygiene in the JIA patients compared to dental patients, based on indices for plaque, decay, and periodontitis. In the JIA patients, plaque microbiota analysis revealed bacteria belonging to genera Haemophilus or Kingella elevated, and Corynebacterium underrepresented. In poly JIA, bacteria belonging to the genus Porphyromonas was overrepresented and Prevotella was underrepresented.

Conclusion

Increased gingival inflammation in JIA was independent of general oral health, and thus cannot be attributed to poor dental hygiene secondary to disability. The variation of microbial profile in JIA patients could indicate a possible link between gingivitis and synovial inflammation.
How healthy is a ‘healthy economy’? Incompatibility between current pathways towards SDG3 and SDG8
Authors: Meurs Mariska , Seidelmann Lisa , Koutsoumpa Myria
Published: December 2019

Background

The interconnections between health and the economy are well known and well documented. The funding gap for realizing SDG3 for good health and well-being, however, remains vast. Simultaneously, economic growth, as expressed and measured in SDG8, continues to leave many people behind. In addition, international financial institutions, notably the International Monetary Fund (IMF), continue to influence the economic and social policies that countries adopt in ways that could undermine achievement of the SDGs. We examine the incoherence between the economic growth and health goals of the SDGs with reference to three East African countries, Malawi, Uganda, and Tanzania, where our organization has been working with partner organizations on SDG related policy analysis and advocacy work.

Results

In all three study countries, some health indicators, notably infant and child mortality, show improvement, but other indicators are lagging behind. Underfunding of the health sector is a major cause for poor health of the population and inequities in access to health care. GDP increases (as a measure of economic growth) do not automatically translate to increases in the countries’ health spending. Health expenditure from domestic public resources remains much lower than the internationally recommended minimum of USD 86 per capita. To achieve this level of health spending from domestic resources only, GDP in these countries would require an unrealistic manifold increase. External aid is proving insufficient to close the funding gap. IMF policy advice and loan conditionality that focus on GDP growth and tight monetary and fiscal targets impair growth in health and social sector spending, while recommended taxation measures are generally regressive.

Conclusions

The existence of the GDP-focused SDG8 can delay efforts towards the achievement of the SDG3 for health and well-being if governments choose to focus on GDP growth without taking sufficient measures to equally distribute wealth and invest in the social sectors, often under the influence of policies advised or conditions put in place by the IMF. Although the IMF has started to acknowledge the importance of social development, its policy advice still adheres to austerity and pro-cyclical economic development harming a country’s population health. To realize the SDGs everywhere, governments should abandon GDP growth as a policy objective and place more emphasis on SDG17 on global co-operation.
Protein tyrosine phosphatase PTPN1 modulates cell growth and associates with poor outcome in human neuroblastoma
Authors: Nunes-Xavier Caroline E. , Aurtenetxe Olaia , Zaldumbide Laura , López-Almaraz Ricardo , Erramuzpe Asier , Cortés Jesús M. , López José I. , Pulido Rafael
Published: December 2019

Background

Protein tyrosine phosphatases (PTPs) regulate neuronal differentiation and survival, but their expression patterns and functions in human neuroblastoma (NB) are scarcely known. Here, we have investigated the function and expression of the non-receptor PTPN1 on human NB cell lines and human NB tumor samples.

Material/methods

NB tumor samples from 44 patients were analysed by immunohistochemistry using specific antibodies against PTPN1, PTPRH, PTPRZ1, and PTEN. PTPN1 knock-down, cell proliferation and tyrosine phosphorylation analyses, and RT-qPCR mRNA expression was assessed on SH-SY5Y, SMS-KCNR, and IMR-32 human NB cell lines.

Results

Knock-down of PTPN1 in SH-SY5Y NB cells resulted in increased tyrosine phosphorylation and cell proliferation. Retinoic acid-mediated differentiation of NB cell lines did not affect PTPN1 mRNA expression, as compared with other PTPs. Importantly, PTPN1 displayed high expression on NB tumors in association with metastasis and poor prognosis.

Conclusions

Our results identify PTPN1 as a candidate regulator of NB cell growth and a potential NB prognostic biomarker.
Patient-specific instrumentation improved three-dimensional accuracy in total knee arthroplasty: a comparative radiographic analysis of 1257 total knee arthroplasties
Authors: Pauzenberger Leo , Munz Martin , Brandl Georg , Frank Julia K. , Heuberer Philipp R. , Laky Brenda , Schwameis Eva , Anderl Werner
Published: December 2019

Background

The purpose of this study was to compare restoration of mechanical limb alignment and three-dimensional component-positioning between conventional and patient-specific instrumentation in total knee arthroplasty.

Methods

Radiographic data of patients undergoing mobile-bearing total knee arthroplasty (n= 1257), using either conventional (n= 442) or patient-specific instrumentation (n= 812), were analyzed. To evaluate accuracy of axis restoration and 3D-component-positioning between conventional and patient-specific instrumentation, absolute deviations from the targeted neutral mechanical limb alignment and planned implant positions were determined. Measurements were performed on standardized coronal long-leg and sagittal knee radiographs. CT-scans were evaluated for accuracy of axial femoral implant rotation. Outliers were defined as deviations from the targeted neutral mechanical axis of > ± 3° or from the intraoperative component-positioning goals of > ± 2°. Deviations greater than ± 5° from set targets were considered to be severe outliers.

Results

Deviations from a neutral mechanical axis (conventional instrumentation: 2.3°± 1.7° vs. patient-specific instrumentation: 1.7°± 1.2°;p< 0.001) and numbers of outliers (conventional instrumentation: 25.8% vs. patient-specific instrumentation: 10.1%;p< 0.001) were significantly lower in the patient-specific instrumentation group. Significantly lower mean deviations and less outliers were detected regarding 3D-component-positioning in the patient-specific instrumentation compared to the conventional instrumentation group (allp< 0.05).

Conclusions

Patient-specific instrumentation prevented from severe limb malalignment and component-positioning outliers (> ± 5° deviation). Use of patient-specific instrumentation proved to be superior to conventional instrumentation in achieving more accurate limb alignment and 3D-component positioning, particularly regarding femoral component rotation. Furthermore, the use of patient-specific instrumentation successfully prevented severe (> 5° deviation) outliers.
Association between the polymorphism of IL-17A and IL-17F gene with knee osteoarthritis risk: a meta-analysis based on case-control studies
Authors: Lu Feifan , Liu Pei , Zhang Qidong , Wang Weiguo , Guo Wanshou
Published: December 2019

Background

Knee osteoarthritis is a joint disease which is characterized by degeneration of articular cartilage and subsequent subchondral bone changes. Polymorphisms of IL-17A/F gene were the recognized candidate genes associated with knee osteoarthritis risk although the results were conflicting. The aim of this study was to determine whether IL-17A(rs2275913) and IL-17F(rs763780) polymorphisms confer susceptibility to knee osteoarthritis.

Method

Literature search was performed in PubMed, Medline, Cochrane Library, Web of science, Embase, and Google Scholar (last search was updated on June 20, 2019), and assessing this association was performed by calculating odds ratios with 95% confidence intervals. Statistical heterogeneity was quantitatively evaluated by using the Q statistic with its p value and I2 statistic.

Result

Six case-control based studies were included involving IL-17A(rs2275913) (2134 cases and 2306 controls) and IL-17F(rs763780) (2134 cases and 2426 controls). The overall analysis suggested that the A allele of the rs2275913 polymorphism, and the C allele of the rs763780 polymorphism in the IL-17 gene may increase the risk of OA. However, subgroup analysis revealed that no association between IL-17A(rs2275913) gene and knee OA risk was found in Caucasian population.

Conclusions

This meta-analysis revealed that the IL-17A(rs2275913) gene polymorphisms may increase the risk of knee OA in Asians, and the IL-17F(rs763780) gene polymorphisms may increase the risk of knee OA both in Asians and Caucasians. However, because of the limitations of the present study, additional larger studies are needed to confirm our findings in the future.
Severe systemic inflammatory response syndrome in patients following Total aortic arch replacement with deep hypothermic circulatory arrest
Authors: Li Jun , Yang Lijing , Wang Guyan , Wang Yuefu , Wang Chunrong , Shi Sheng
Published: December 2019

Background

This cohort study aims to retrospectively investigate the incidence of severe systemic inflammatory response syndrome (sSIRS) in patients following total aortic arch replacement (TAR) under deep hypothermic circulatory arrest (DHCA) with selective cerebral perfusion and its effect on clinical outcomes.

Methods

All patients who underwent TAR with DHCA were consecutively enrolled from January 2013 until December 2015 at our institute. sSIRS was diagnosed between 12 and 48 h postoperatively if patients met all four criteria of the SIRS definition.

Results

Of the 522 patients undergoing TAR with DHCA, 31.4% developed sSIRS. Patients aged under 60 yr were characterized by a higher prevalence of sSIRS (OR = 2.93; 95% CI 2.01–4.28; P <0.001). Higher baseline serum creatinine (OR = 1.61; 95% CI 1.18–2.20; P = 0.003), concomitant coronary disease (OR = 2.00; 95% CI 1.15–3.48; P = 0.015) and extended cardiopulmonary time (OR = 1.63; 95% CI 1.23–2.18; P = 0.001) independently contributed to a greater likelihood of postoperative sSIRS onset, while the preferred administration of ulinastatin (OR = 0.69; 95% CI 0.51–0.93; P = 0.015) and dexmedetomidine (OR = 0.36; 95% CI 0.23–0.56; P < 0.001) attenuated it. Patients with sSIRS had a greater risk of developing postoperative major adverse complications compared with the no sSIRS group [56.7%(93/164) vs 26.8% (96/358), P < 0.001]. sSIRS was found to be a significant risk factor for major adverse complications (OR, 4.52; 95% CI, 3.40–6.01; P < 0.001). A significant difference was revealed in in-hospital death following TAR between the sSIRS group and the no-sSIRS group [4.88% (8/164) vs 1.12% (4/358), P = 0.019]. The Kaplan-Meier curve indicated that the time to discharge from the intensive care unit was significantly prolonged in the sSIRS group compared with patients without it (log-rank p < 0.001).

Conclusions

sSIRS occurs commonly in patients following TAR with DHCA. There is an inverse association between age and sSIRS onset, whereby age over 60 yr can lower the risk of it. sSIRS development can increase the likelihood of major postoperative major adverse events.
Pilot experience of multidisciplinary team discussion dedicated to inherited pulmonary fibrosis
Authors: Borie Raphael , Kannengiesser Caroline , Gouya Laurent , Dupin Clairelyne , Amselem Serge , Ba Ibrahima , Bunel Vincent , Bonniaud Philippe , Bouvry Diane , Cazes Aurélie , Clement Annick , Debray Marie Pierre , Dieude Philippe , Epaud Ralph , Fanen Pascale , Lainey Elodie , Legendre Marie , Plessier Aurélie , Sicre de Fontbrune Flore , Wemeau-Stervinou Lidwine , Cottin Vincent , Nathan Nadia , Crestani Bruno
Published: December 2019

Background

Genetic testing is proposed for suspected cases of monogenic pulmonary fibrosis, but clinicians and patients need specific information and recommendation about the related diagnosis and management issues. Because multidisciplinary discussion (MDD) has been shown to improve accuracy of interstitial lung disease (ILD) diagnosis, we evaluated the feasibility of a genetic MDD (geneMDD) dedicated to the indication for and interpretation of genetic testing. The geneMDD group met monthly and included pediatric and adult lung specialists with ILD expertise, molecular and clinical geneticists, and one radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend.

Results

Since 2016, physicians from 34 different centers in 7 countries have participated in the geneMDD. The medical files of 95 patients (53 males) have been discussed. The median age of patients was 43 years [range 0–77], 10 were ≤ 15 years old, and 6 were deceased at the time of the discussion. Among 85 analyses available, the geneMDD considered the rare gene variants pathogenic for 61: 37 variants in telomere-related genes, 23 variants in surfactant-related genes and 1 variant in MARS. Genetic counseling was offered for relatives of these patients. The geneMDD therapeutic proposals were as follows: antifibrotic drugs (n = 25), steroids or immunomodulatory therapy (n = 18), organ transplantation (n = 21), watch and wait (n = 21), or best supportive care (n = 4).

Conclusion

Our experience shows that a dedicated geneMDD is feasible regardless of a patient’s age and provides a unique opportunity to adapt patient management and therapy in this very rare condition.
Vitamin D, gut microbiota, and radiation-related resistance: a love-hate triangle
Authors: Huang Ruixue , Xiang Jing , Zhou Pingkun
Published: December 2019

Radiation resistance is a serious issue in radiotherapy. Increasing evidence indicates that the human gut microbiome plays a role in the development of radiation resistance. Vitamin D is an important supplement for cancer patients treated with radiotherapy. Against this background, this paper reviewed research regarding the associations among vitamin D, microbiota dysbiosis, and radiation resistance. A hypothesis is developed to describe the relationships among vitamin D, the gut microbiota, and radiotherapy outcomes. Radiotherapy changes the composition of the gut microbiota, which in turn influence the serum level of vitamin D, and its distribution and metabolism in the body. Alteration of vitamin D level influences the patient response to radiotherapy, where the underlying mechanisms may be associated with the intestinal microenvironment, immune molecules in the intestines, gut microbiome metabolites, and signaling pathways associated with vitamin D receptors. Our understanding of the contribution of vitamin D and the gut microbiota to radiotherapy outcomes has been increasing gradually. A better understanding of the relationships among vitamin D, the gut microbiota, and radiotherapy outcomes will shed more light on radiation resistance, and also promote the development of new strategies for overcoming it, thus addressing an important challenge associated with the currently available radiotherapy modalities for cancer patients.
Continual measurement of arterial dP/dtmax enables minimally invasive monitoring of left ventricular contractility in patients with acute heart failure
Authors: Ostadal Petr , Vondrakova Dagmar , Krüger Andreas , Janotka Marek , Naar Jan
Published: December 2019

Background

Continuous, reliable evaluation of left ventricular (LV) contractile function in patients with advanced heart failure requiring intensive care remains challenging. Continual monitoring of dP/dtmax from the arterial line has recently become available in hemodynamic monitoring. However, the relationship between arterial dP/dtmax and LV dP/dtmax remains unclear. This study aimed to determine the relationship between arterial dP/dtmax and LV dP/dtmax assessed using echocardiography in patients with acute heart failure.

Methods

Forty-eight patients (mean age 70.4 years [65% male]) with acute heart failure requiring intensive care and hemodynamic monitoring were recruited. Hemodynamic variables, including arterial dP/dtmax, were continually monitored using arterial line pressure waveform analysis. LV dP/dtmax was assessed using continuous-wave Doppler analysis of mitral regurgitation flow.

Results

Values from continual arterial dP/dtmax monitoring were significantly correlated with LV dP/dtmax assessed using echocardiography (r = 0.70 [95% confidence interval (CI) 0.51–0.82]; P < 0.0001). Linear regression analysis revealed that LV dP/dtmax = 1.25 × (arterial dP/dtmax) (P < 0.0001). Arterial dP/dtmax was also significantly correlated with stroke volume (SV) (r = 0.63; P < 0.0001) and cardiac output (CO) (r = 0.42; P = 0.0289). In contrast, arterial dP/dtmax was not correlated with SV variation, dynamic arterial elastance, heart rate, systemic vascular resistance (SVR), or mean arterial pressure. Markedly stronger agreement between arterial and LV dP/dtmax was observed in subgroups with higher SVR (N = 28; r = 0.91; P <  0.0001), lower CO (N = 26; r = 0.81; P <  0.0001), and lower SV (N = 25; r = 0.60; P = 0.0014). A weak correlation was observed in the subjects with lower SVR (N = 20; r = 0.61; P = 0.0004); in the subgroups with higher CO (N = 22) and higher SV (N = 23), no significant correlation was found.

Conclusion

Our results suggest that in patients with acute heart failure requiring intensive care with an arterial line, continuous calculation of arterial dP/dtmax may be used for monitoring LV contractility, especially in those with higher SVR, lower CO, and lower SV, such as in patients experiencing cardiogenic shock. On the other hand, there was only a weak or no significant correlation in the subgroups with higher CO, higher SV, and lower SVR.
Predicting the clinical trajectory in critically ill patients with sepsis: a cohort study
Authors:   on behalf of the MARS consortium, Klein Klouwenberg Peter M. C. , Spitoni Cristian , van der Poll Tom , Bonten Marc J. , Cremer Olaf L.
Published: December 2019

Background

To develop a mathematical model to estimate daily evolution of disease severity using routinely available parameters in patients admitted to the intensive care unit (ICU).

Methods

Over a 3-year period, we prospectively enrolled consecutive adults with sepsis and categorized patients as (1) being at risk for developing (more severe) organ dysfunction, (2) having (potentially still reversible) limited organ failure, or (3) having multiple-organ failure. Daily probabilities for transitions between these disease states, and to death or discharge, during the first 2 weeks in ICU were calculated using a multi-state model that was updated every 2 days using both baseline and time-varying information. The model was validated in independent patients.

Results

We studied 1371 sepsis admissions in 1251 patients. Upon presentation, 53 (4%) were classed at risk, 1151 (84%) had limited organ failure, and 167 (12%) had multiple-organ failure. Among patients with limited organ failure, 197 (17%) evolved to multiple-organ failure or died and 809 (70%) improved or were discharged alive within 14 days. Among patients with multiple-organ failure, 67 (40%) died and 91 (54%) improved or were discharged. Treatment response could be predicted with reasonable accuracy (c-statistic ranging from 0.55 to 0.81 for individual disease states, and 0.67 overall). Model performance in the validation cohort was similar.

Conclusions

This prediction model that estimates daily evolution of disease severity during sepsis may eventually support clinicians in making better informed treatment decisions and could be used to evaluate prognostic biomarkers or perform in silico modeling of novel sepsis therapies during trial design.

Clinical trial registration

ClinicalTrials.gov NCT01905033
PASTMUS: mapping functional elements at single amino acid resolution in human cells
Authors: Zhang Xinyi , Yue Di , Wang Yinan , Zhou Yuexin , Liu Ying , Qiu Yeting , Tian Feng , Yu Ying , Zhou Zhuo , Wei Wensheng
Published: December 2019

Identification of functional elements for a protein of interest is important for achieving a mechanistic understanding. However, it remains cumbersome to assess each and every amino acid of a given protein in relevance to its functional significance. Here, we report a strategy, PArsing fragmented DNA Sequences from CRISPR Tiling MUtagenesis Screening (PASTMUS), which provides a streamlined workflow and a bioinformatics pipeline to identify critical amino acids of proteins in their native biological contexts. Using this approach, we map six proteins—three bacterial toxin receptors and three cancer drug targets, and acquire their corresponding functional maps at amino acid resolution.
SyRI: finding genomic rearrangements and local sequence differences from whole-genome assemblies
Authors: Goel Manish , Sun Hequan , Jiao Wen-Biao , Schneeberger Korbinian
Published: December 2019

Genomic differences range from single nucleotide differences to complex structural variations. Current methods typically annotate sequence differences ranging from SNPs to large indels accurately but do not unravel the full complexity of structural rearrangements, including inversions, translocations, and duplications, where highly similar sequence changes in location, orientation, or copy number. Here, we present SyRI, a pairwise whole-genome comparison tool for chromosome-level assemblies. SyRI starts by finding rearranged regions and then searches for differences in the sequences, which are distinguished for residing in syntenic or rearranged regions. This distinction is important as rearranged regions are inherited differently compared to syntenic regions.
Delivery of home-based postpartum contraception in rural Guatemalan women: a cluster-randomized trial protocol
Authors: Harrison Margo S. , Bunge-Montes Saskia , Rivera Claudia , Jimenez-Zambrano Andrea , Heinrichs Gretchen , Scarbro Sharon , Juarez-Colunga Elizabeth , Bolanos Antonio , Asturias Edwin , Berman Stephen , Sheeder Jeanelle
Published: December 2019

Background

Postpartum contraception is important to prevent unintended and closely spaced pregnancies following childbirth.

Methods

This study is a cluster-randomized trial of communities in rural Guatemala where women receive ante- and postnatal care through a community-based nursing program. When nurses visit women for their postpartum visit in the intervention clusters, instead of providing only routine care that includes postpartum contraceptive education and counseling, the nurses will also bring a range of barrier, short-acting, and long-acting contraceptives that will be offered and administered in the home setting, after routine clinical care is provided.

Discussion

A barrier to postpartum contraception is access to medications and devices. Our study removes some access barriers (distance, time, cost) by providing contraception in the home. We also trained community nurses to place implants, which are a type of long-acting reversible contraceptive method that was previously only available in the closest town which is about an hour away by vehicular travel. Therefore, our study examines how home-based delivery of routinely available contraceptives and the less routinely available implant may be associated with increased uptake of postpartum contraception within 3 months of childbirth. The potential implications of this study include that nurses may be able to be trained to safely provide contraceptives, including placing implants, in the home setting, and provision of home-based contraception may be an effective way of delivering an evidence-based intervention for preventing unintended and closely spaced pregnancies in the postpartum period.

Trial registration

Clinicaltrials.gov, NCT04005391. Retrospectively registered on 1 July 2019.