bluuebunny/crossref_metadata_2025 huggingface dataset:
Achieving Successful Outcomes of Hip Arthroscopy in the Setting of Generalized Ligamentous Laxity with Labral Preservation and Appropriate Capsular Management: A Matched Pair Controlled Study
Authors: Domb Benjamin , Chen Jeffrey , Rosinsky Philip , Shapira Jacob , Lall Ajay , Yelton Mitchell , Brayboy Ciaron , Maldonado David
Published: July 2020

Objectives:

(1) To report minimum two-year PROs in patients with generalized ligamentous laxity (GLL) who underwent hip arthroscopy and (2) to compare clinical results to a matched-pair control group without GLL.

Methods:

Data from a prospectively collected database was retrospectively reviewed between August 2014 and December 2016. Patients were considered eligible if they received primary arthroscopic treatment for symptomatic labral tears and femoroacetabular impingement (FAI). Inclusion criteria included preoperative and minimum two-year follow-up scores for the following PROs: modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score-Sports Specific Scale (HOS-SSS), and Visual Analogue Scale (VAS). Patients were excluded if they had preoperative Tönnis ≥ 2, ipsilateral hip condition, prior hip surgery, worker’s compensation status, or dysplasia. From the sample population, two groups were created: the GLL group (Beighton ≥ 4) and the control group (Beighton < 4). Patients were matched in a 1:2 ratio via propensity-score matching according to age, gender, body mass index (BMI), acetabular and femoral head Outerbridge grade, and preoperative lateral center-edge angle (LCEA). Patient Acceptable Symptomatic State (PASS) and Minimal Clinically Important Difference (MCID) for mHHS and HOS-SSS were calculated. PASS was also calculated for International Hip Outcome Tool-12 (iHOT-12) as well as MCID for VAS. Significant differences were noted if P < 0.05.

Results:

95 patients with GLL were matched to 143 control patients. Age, gender, BMI, and follow-up times were not different (P > 0.05). Preoperative radiographic measurements demonstrated no difference. Intraoperative findings and procedures between groups were similar except for capsular treatment, with the GLL group receiving more plications (P = 0.004). Both groups reported similar baseline PROs and VAS. At minimum two-year follow-up both groups showed significant improvement in PROs and VAS (P < 0.001), furthermore, the postoperative PROs at minimum two-year follow-up showed no difference (P > 0.05) and the magnitude of improvement (delta value) was similar for mHHS (P = 0.93), NAHS (P = 0.809), HOS-SSS (0.398) and VAS (P = 0.824). Moreover, groups reached comparable rates of MCID and/or PASS for mHHS, HOS-SSS, iHOT-12, and VAS.

Conclusions:

Patients with GLL following hip arthroscopy for symptomatic FAI and labral tears, may expect favorable outcomes with appropriate labral and capsular management at minimum two-year follow-up. When compared to a pair-matched control group without GLL, results were comparable for mHHS, NAHS, HOS-SSS, VAS and reaching PASS and/or MCID for mHHS, HOS-SSS, iHOT-12 and VAS.
What Are the Outcomes of Meniscus Repair vs Excision in Stable Knees in High School and College Athletes: A Prospective Cohort Study
Authors:   Cleveland Clinic Sports Health Group, Egger Anthony , Flynn Megan , Jin Yuxuan , Strnad Greg , Spindler Kurt , Saluan Paul
Published: July 2020

Objectives:

In high school and college athletes, the results of isolated meniscectomy compared to meniscal repair in ligamentously stable knees is unknown. Our objective was to compare patient-reported outcomes and reoperation rates at a minimum 1 year of follow-up for high school and college athletes undergoing isolated meniscal repair compared to meniscectomy. We hypothesized that both groups would see significant improvement in outcomes with meniscectomy having higher reported outcomes and a lower reoperation rate compared to meniscal repair.

Methods:

Patients aged 13-22 years old undergoing meniscal surgery at a single institution between 2015-2017 were prospectively enrolled and followed in our outcomes management evaluation system (OME). Pre-operatively, patients’ baseline demographics and patient-reported outcomes (PROMs) specific to meniscal pathology were collected, including Knee Injury and Osteoarthritis Outcome Score (KOOS) pain and quality of life (QoL) subsets. Post-operatively, intra-operative findings and treatments were recorded from OME. Patients were contacted and completed a minimum 1- or 2-year patient-reported outcome measures survey. Embedded in the post-operative survey was a question designed to evaluate the Patient Acceptable Symptom State (PASS). Patients were also specifically asked if they had undergone any subsequent surgeries to either knee since their primary procedure as a preliminary assessment of early failure.

Results:

A total of 145 patients were enrolled (70% male; median age, 18 years). One-year minimum PROMs were obtained on 73% (n=106) of the cohort. The results are displayed in the table and figure. KOOS QoL (see figure) and pain scores at minimum 1-year follow-up were not significantly different between meniscal repair compared to meniscectomy. Reoperation rate was 7.5% overall with no significant difference noted between the groups. No individual variables, including body mass index (BMI), smoking, level of education, mental health status, or grade 3 or 4 cartilage lesions were found not to be significant risk factors for outcome in either group. A PASS was achieved in 82% of the meniscectomy group and 71% of the meniscal repair group.

Conclusion:

High school and college athletes undergoing isolated meniscal surgery had equally significant improvements in minimum 1-year PROMs regardless of whether they underwent meniscectomy or meniscal repair. Preliminary reoperation rates were similar amongst the two treatment groups and the majority of both groups achieved a patient acceptable symptom state. No individual variable was identified as a modifiable risk factor to poor outcome after isolated meniscal surgery in this age group. [Figure: see text]
Morphological and Functional Outcomes >13 Years After Achilles Tendon Rupture Treated Operatively and Non-operatively
Authors: Willits Kevin , Birmingham Trevor , Spouge Alison , Bryant Dianne , Khan Michaela
Published: July 2020

Objectives:

In patients >13yrs after treatment for acute Achilles tendon rupture (AATR), 1) investigate side-to-side differences in MRI-defined morphological changes in the Achilles tendon and surrounding calf musculature, 2) investigate side-to-side differences in single-limb functional tasks, and 3) compare patients who received operative vs non-operative treatment.

Methods:

28 patients (11 operative, 17 non-operative) from a previous randomized trial returned 15±1 years post-AATR for testing (age: 57±7 years; BMI: 30±5 kg/m2). Patients underwent bilateral 3T MRI (MAGNETOM Prisma, Siemens) including sagittal and axial T1 and T2-weighted turbo spin echo (TSE), axial T1-weighted inversion recovery, and sagittal T2-weighted 3D isotropic TSE sequences. The maximum anteroposterior Achilles tendon diameter (MAD) and cross-sectional area (CSA), distance from the MAD to the superior margin of the calcaneus, tendon length, gastrocnemius and soleus CSA, and calf circumference were measured using distance and area software tools (Figure 1; AGFA Healthcare). Functional measures included single-legged heel-rise repetitions and maximum vertical jump height. All outcomes were compared between limbs and between groups.

Results:

Overall, there were significant side-to-side differences in most MRI and functional measures, with the injured limb Achilles tendon typically wider and thicker (MAD often twice as large), calf musculature CSA smaller, number of heel raises lower, and vertical jump height lower (Table 1). The only differences between treatment groups was in MAD and the distance from the MAD to the superior margin of the calcaneus, with a greater side-to-side difference for patients treated operatively (Table 1).

Conclusion:

Substantial side-to-side differences in tendon diameter, thickness, muscle bulk and functional performance persist beyond a decade after treatment for AATR. There were no differences favoring operative treatment over non-operative treatment.
Oral Health Inequalities among Indigenous and Non-Indigenous Children
Authors: Haag D. , Schuch H. , Ha D. , Do L. , Jamieson L.
Published: July 2020

Introduction:

Our ability to address child oral health inequalities would be greatly facilitated by a more nuanced understanding of whether underlying disease experience or treatment opportunities account for a larger share of differences between social groups. This is particularly relevant in the context of population subgroups who are socially marginalized, such as Australia’s Indigenous population. The decayed, missing, and filled (dmf) surfaces index is at once a reflection of dental caries experience (d) and its management (m and f).

Objectives:

To 1) describe socioeconomic inequalities in dental caries experience and its management among Indigenous and non-Indigenous children and 2) compare these inequalities using absolute and relative measures.

Methods:

Data were from the Australian National Child Oral Health Study 2012–2014. Absolute and relative income inequalities were assessed for overall dmfs and its individual components (ds, ms, fs) using adjusted means and health disparity indices (Slope Index of Inequality [SII] and Relative Index of Inequality [RII]).

Results:

Mean dmfs among Indigenous children aged 5 to 10 y was 6.4 (95% confidence interval [CI], 5.4–7.4), ranging from 2.3 in the highest to 9.1 in the lowest income group. Mean dmfs among non-Indigenous children was 2.9 (95% CI, 2.8–3.1), ranging from 1.9 in the highest to 4.2 in the lowest income group. Age- and gender-adjusted social gradients for Indigenous children were evident across all dmfs components but were particularly notable for ds (SII = −4.6, RII = −1.7) and fs (SII = −3.2, RII = −1.5). The social gradients for non-Indigenous children were much lower in magnitude: ds (SII = −1.8, RII = −1.6) and fs (SII = −0.7, RII = −0.5).

Conclusion:

Our findings suggest that socioeconomic disadvantage may translate into both higher disease experience and increased use of dental services for both Indigenous and non-Indigenous groups, with the social gradients being much more amplified among Indigenous children.

Knowledge Transfer Statement:

The findings of this study demonstrate the magnitude of disparities in dental caries among children by population groups in Australia. Our results suggest that the relationship between socioeconomic disadvantage and poor oral health is more deleterious among Indigenous than non-Indigenous children. Tackling upstream determinants of health might not only affect population patterns of health and disease but also mitigate the overwhelming racial inequalities in oral health between Indigenous and non-Indigenous Australians.
Simulation of Pediatric Endoscopic Cricoid Reduction and Expansion
Authors: Scholp Austin J. , Hoffman Matthew R. , De Alarcon Alessandro , Gerber Mark E. , Jiang Jack J. , McMurray James Scott
Published: July 2020

Endoscopic cricoid expansion and reduction are newer approaches to the management of pediatric bilateral vocal fold immobility and postlaryngotracheal reconstruction glottic insufficiency, respectively. These procedures offer a less invasive, endoscopic alternative to procedures that typically required open management with a more prolonged recovery. These technically demanding procedures are currently performed only in select centers, and there is no currently described training model for practicing them. We present a modification to a laryngeal dissection station that allows for simulation of endoscopic cricoid reduction and expansion with excised larynges. The model allows trainees to practice endoscopic posterior cricoid exposure, incision of the cricoid cartilage, placement of a simulated costal cartilage graft for expansion, and endoscopic suturing for reduction. Development of simulators for procedures that are infrequently performed have the potential to help trainees reach surgical competency faster and more safely.
TET family dioxygenases and the TET activator vitamin C in immune responses and cancer
Authors: Yue Xiaojing , Rao Anjana
Published: July 2020

Vitamin C serves as a cofactor for Fe(II) and 2-oxoglutarate–dependent dioxygenases including TET family enzymes, which catalyze the oxidation of 5-methylcytosine into 5-hydroxymethylcytosine and further oxidize methylcytosines. Loss-of-function mutations in epigenetic regulators such as TET genes are prevalent in hematopoietic malignancies. Vitamin C deficiency is frequently observed in cancer patients. In this review, we discuss the role of vitamin C and TET proteins in cancer, with a focus on hematopoietic malignancies, T regulatory cells, and other immune system cells.
MutEnricher: a flexible toolset for somatic mutation enrichment analysis of tumor whole genomes
Authors: Soltis Anthony R. , Dalgard Clifton L. , Pollard Harvey B. , Wilkerson Matthew D.
Published: July 2020

Background

Analysis of somatic mutations from tumor whole exomes has fueled discovery of novel cancer driver genes. However, ~ 98% of the genome is non-coding and includes regulatory elements whose normal cellular functions can be disrupted by mutation. Whole genome sequencing (WGS), on the other hand, allows for identification of non-coding somatic variation and expanded estimation of background mutation rates, yet fewer computational tools exist for specific interrogation of this space.

Results

We present MutEnricher, a flexible toolset for investigating somatic mutation enrichment in both coding and non-coding genomic regions from WGS data. MutEnricher contains two distinct modules for these purposes that provide customizable options for calculating sample- and feature-specific background mutation rates. Additionally, both MutEnricher modules calculate feature-level and local, or “hotspot,” somatic mutation enrichment statistics.

Conclusions

MutEnricher is a flexible software package for investigating somatic mutation enrichment that is implemented in Python, is freely available, can be efficiently parallelized, and is highly configurable to researcher's specific needs. MutEnricher is available online athttps://github.com/asoltis/MutEnricher.
IDSSIM: an lncRNA functional similarity calculation model based on an improved disease semantic similarity method
Authors: Fan Wenwen , Shang Junliang , Li Feng , Sun Yan , Yuan Shasha , Liu Jin-Xing
Published: July 2020

Background

It has been widely accepted that long non-coding RNAs (lncRNAs) play important roles in the development and progression of human diseases. Many association prediction models have been proposed for predicting lncRNA functions and identifying potential lncRNA-disease associations. Nevertheless, among them, little effort has been attempted to measure lncRNA functional similarity, which is an essential part of association prediction models.

Results

In this study, we presented an lncRNA functional similarity calculation model, IDSSIM for short, based on an improved disease semantic similarity method, highlight of which is the introduction of information content contribution factor into the semantic value calculation to take into account both the hierarchical structures of disease directed acyclic graphs and the disease specificities. IDSSIM and three state-of-the-art models, i.e., LNCSIM1, LNCSIM2, and ILNCSIM, were evaluated by applying their disease semantic similarity matrices and the lncRNA functional similarity matrices, as well as corresponding matrices of human lncRNA-disease associations coming from either lncRNADisease database or MNDR database, into an association prediction method WKNKN for lncRNA-disease association prediction. In addition, case studies of breast cancer and adenocarcinoma were also performed to validate the effectiveness of IDSSIM.

Conclusions

Results demonstrated that in terms of ROC curves and AUC values, IDSSIM is superior to compared models, and can improve accuracy of disease semantic similarity effectively, leading to increase the association prediction ability of the IDSSIM-WKNKN model; in terms of case studies, most of potential disease-associated lncRNAs predicted by IDSSIM can be confirmed by databases and literatures, implying that IDSSIM can serve as a promising tool for predicting lncRNA functions, identifying potential lncRNA-disease associations, and pre-screening candidate lncRNAs to perform biological experiments. The IDSSIM code, all experimental data and prediction results are available online at https://github.com/CDMB-lab/IDSSIM.
Ecomorphological divergence and habitat lability in the context of robust patterns of modularity in the cichlid feeding apparatus
Authors: Conith Andrew J. , Kidd Michael R. , Kocher Thomas D. , Albertson R. Craig
Published: July 2020

Background

Adaptive radiations are characterized by extreme and/or iterative phenotypic divergence; however, such variation does not accumulate evenly across an organism. Instead, it is often partitioned into sub-units, or modules, which can differentially respond to selection. While it is recognized that changing the pattern of modularity or the strength of covariation (integration) can influence the range or rate of morphological evolution, the relationship between shape variation and covariation remains unclear. For example, it is possible that rapid phenotypic change requires concomitant changes to the underlying covariance structure. Alternatively, repeated shifts between phenotypic states may be facilitated by a conserved covariance structure. Distinguishing between these scenarios will contribute to a better understanding of the factors that shape biodiversity. Here, we explore these questions using a diverse Lake Malawi cichlid species complex,Tropheops,that appears to partition habitat by depth.

Results

We construct a phylogeny ofTropheopspopulations and use 3D geometric morphometrics to assess the shape of four bones involved in feeding (mandible, pharyngeal jaw, maxilla, pre-maxilla) in populations that inhabit deep versus shallow habitats. We next test numerous modularity hypotheses to understand whether fish at different depths are characterized by conserved or divergent patterns of modularity. We further examine rates of morphological evolution and disparity between habitats and among modules. Finally, we raise a singleTropheopsspecies in environments mimicking deep or shallow habitats to discover whether plasticity can replicate the pattern of morphology, disparity, or modularity observed in natural populations.

Conclusions

Our data support the hypothesis that conserved patterns of modularity permit the evolution of divergent morphologies and may facilitate the repeated transitions between habitats. In addition, we find the lab-reared populations replicate many trends in the natural populations, which suggests that plasticity may be an important force in initiating depth transitions, priming the feeding apparatus for evolutionary change.
MicroRNA-138 promotes neuroblastoma SH-SY5Y cell apoptosis by directly targeting DEK in Alzheimer’s disease cell model
Authors: Miao Jin , Jing Jin , Shao Yixiang , Sun Huaichang
Published: July 2020

Background

Alzheimer’s disease (AD) is a progressive neuro-degenerative disease with a major manifestation of dementia. MicroRNAs were reported to regulate the transcript expression in patients with Alzheimer’s disease (AD). In this study, we investigated the roles of miR-138, a brain-enriched miRNA, in the AD cell model.

Methods

The targets of miRNA-138 was predicted by bioinformatic analysis. The expression levels of DEK at both mRNA and protein levels were determined by qRT-PCR and Western blot, respectively. Luciferase assays were carried out to examine cell viabilities. Hoechst 33258 staining was used to detect cell apoptosis.

Results

Our results demonstrated that the expression levels of miR-138 were increased in AD model, and DEK was a target of miR-138. Overexpression of miR-138 in SH-SY5Y cells obviously down-regulated the expression of DEK in SH-SY5Y cells, resulting in the inactivation of AKT and increased expression levels of proapoptotic caspase-3. MiR-138 mediated-suppression of DEK increased the susceptibility of cell apoptosis.

Conclusions

MicroRNA-138 promotes cell apoptosis of SH-SY5Y by targeting DEK in SH-SY5Y AD cell model. The regulation of miR-138 may contribute to AD via down-regulation of the DEK/AKT pathway.
Early post-stress decrease in cardiac performance by impedance cardiography and its relationship to the severity and extent of ischemia by myocardial perfusion imaging
Authors: Goldkorn Ronen , Naimushin Alexey , Rozen Eli , Freimark Dov
Published: July 2020

Background

While single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a well-established noninvasive procedure for the evaluation of patients with coronary artery disease (CAD), it is unable to detect the presence of, or underestimates the extent of CAD in certain patients. We aimed to show that a bio-impedance device can detect early post-stress changes in several hemodynamic parameters, thereby serving as a potential marker for the presence of significant ischemia.

Methods

Prospectively enrolled patients, referred to our Medical Center for clinically-indicated MPI, underwent testing using a Non-Invasive Cardiac System (NICaS) before and immediately after exercise. The differences between rest and stress hemodynamic parameters were compared with the severity and extent of myocardial ischemia by MPI. The study included 198 patients; mean age was 62 years, 26% were women, 54% had hypertension, and 29% diabetes mellitus. Of them, 188 patients had ≤10%, and 10 had > 10% of myocardial ischemia.

Results

In the first group, there was a significantly greater increase in post-exercise stroke index, stroke work index, cardiac index and cardiac power index (19.2, 29.1, 90.5 and 107%, respectively) compared with the second group (− 2.7, 3.8, 43.7 and 53.5%, respectively), as well as a significantly greater decrease in total peripheral resistance index (− 38.7% compared with − 16.3%), with corresponding p values of 0.015, 0.017, 0.040, 0.016, and < 0.001, respectively.

Conclusions

Our data suggest that immediate post-stress changes in several hemodynamic parameters, detected by the NICaS, can be used as an important adjunct to SPECT MPI for the early detection of myocardial ischemia.
A descriptive study of orthopaedic injuries due to parachute jumping in soldiers
Authors: Sahin Taner , Batın Sabri
Published: July 2020

Background

While parachute jumping, soldiers may suffer minor or life-threatening injuries in various parts of the body. Several trauma scoring systems assess the severity of such injuries. The primary goal of this study was to assess clinical characteristics and the severity of orthopaedic, musculoskeletal, and other injuries from military training-related parachute jumping using two trauma scoring systems (AIS and ISS). Our secondary goal was to assess whether there was an increase in injury rates with age.

Methods

In total, 185 military personnel between 19 and 51 years old who were injured as a result of daytime static parachute jumping during 44 months between January 2016 and August 2019 were included in the study. Demographic data; vital signs; the level of consciousness; the Glasgow Coma Scale; ISS trauma region classifications; anatomical injury sites; AIS and ISS scores; diagnoses; treatment methods; hospitalization status; and duration of hospital stay were examined descriptively.

Results

There were 184 male and one female participant. The most commonly injured body site was the foot (33.5%), and the most common diagnosis was soft tissue trauma (64.3%). The most commonly injured body site was the foot (33.5%), and the most common diagnosis was soft tissue trauma (64.3%). Regarding treatment methods, 51.4% received analgesic pills and cold pack application, 42.7% received a plaster splint, and 5.9% had orthopaedic surgery. The mean ISS score was 5.16 ± 3.92. The hospitalization rate was significantly higher for patients with a critical AIS score than those with a severe AIS score (p < 0.001).

Conclusions

The use of trauma scoring systems to assess injury severity among patients admitted to an ED due to a parachute jumping injury may facilitate treatment selection. We found that AIS and ISS were useful in determining injury severity. Therefore, we recommend the use of trauma scoring systems for assessing the injury severity and the therapeutic approach, and we advocate for the use of the 17 anatomical regions we used in this study. We also found that with increasing age, the severity of injury could increase.
Increasing prevalence of anticholinergic medication use in older people in England over 20 years: cognitive function and ageing study I and II
Authors: Grossi Carlota M. , Richardson Kathryn , Savva George M. , Fox Chris , Arthur Antony , Loke Yoon K. , Steel Nicholas , Brayne Carol , Matthews Fiona E. , Robinson Louise , Myint Phyo K. , Maidment Ian D.
Published: July 2020

Background

Anticholinergic medication use is linked with increased cognitive decline, dementia, falls and mortality, and their use should be limited in older people. Here we estimate the prevalence of anticholinergic use in England’s older population in 1991 and 2011, and describe changes in use by participant’s age, sex, cognition and disability.

Methods

We compared data from participants aged 65+ years from the Cognitive Function and Ageing Studies (CFAS I and II), collected during 1990–1993 (N = 7635) and 2008–2011 (N = 7762). We estimated the prevalence of potent anticholinergic use (Anticholinergic Cognitive Burden [ACB] score = 3) and average anticholinergic burden (sum of ACB scores), using inverse probability weights standardised to the 2011 UK population. These were stratified by age, sex, Mini-Mental State Examination score, and activities of daily living (ADL) or instrumental ADL (IADL) disability.

Results

Prevalence of potent anticholinergic use increased from 5.7% (95% Confidence Interval [CI] 5.2–6.3%) of the older population in 1990–93 to 9.9% (9.3–10.7%) in 2008–11, adjusted odds ratio of 1.90 (95% CI 1.67–2.16). People with clinically significant cognitive impairment (MMSE [Mini Mental State Examination] 21 or less) were the heaviest users of potent anticholinergics in CFAS II (16.5% [95% CI 12.0–22.3%]). Large increases in the prevalence of the use medication with ‘any’ anticholinergic activity were seen in older people with clinically significant cognitive impairment (53.3% in CFAS I to 71.5% in CFAS II).

Conclusions

Use of potent anticholinergic medications nearly doubled in England’s older population over 20 years with some of the greatest increases amongst those particularly vulnerable to anticholinergic side-effects.
Machine learning reveals that Mycobacterium tuberculosis genotypes and anatomic disease site impacts drug resistance and disease transmission among patients with proven extra-pulmonary tuberculosis
Authors: Sibandze Doctor B. , Magazi Beki T. , Malinga Lesibana A. , Maningi Nontuthuko E. , Shey Bong-Akee , Pasipanodya Jotam G. , Mbelle Nontombi N.
Published: July 2020

Background

There is a general dearth of information on extrapulmonary tuberculosis (EPTB). Here, we investigated Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane metropolitan area, in South Africa.

Methods

Consecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. MTBDRplus assay was used to search mutations for isoniazid and rifampin resistance. Machine learning algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and corresponding 95% confidence intervals (CI).

Results

Of the 70 isolates examined, the largest cluster comprised 25 (36%) Mtb strains that belonged to the East Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when compared to the Euro-American and East-African Indian lineages: OR = 10.11 (95% CI: 1.56–116). Lymphadenitis, meningitis and cutaneous TB, were significantly more likely to be associated with drug resistance: OR = 12.69 (95% CI: 1.82–141.60) and AR = 0.25 (95% CI: 0.06–0.43) when compared with other EPTB sites, which suggests that poor rifampin penetration might be a contributing factor.

Conclusions

The majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the development of resistance.
Listeria spondylodiscitis: an uncommon etiology of a common condition; a case report
Authors: Al Ohaly Rand , Ranganath Nischal , Saffie Medina G. , Shroff Anjali
Published: July 2020

Background

Listeriosis is a severe food-borne infection caused by the Gram-positive rod, Listeria monocytogenes. Despite the low incidence (3–8 cases per million), Listeriosis has a case fatality rate of 20–30% as it occurs predominantly in immunocompromised individuals at extremes of age, diabetics and pregnant women. Listeriosis classically presents as a febrile gastroenteritis, isolated bacteremia, meningitis, or maternal-fetal infections. Focal bone and joint infection are rare and primarily involve orthopedic implant devices. Here, we present the first case of Listeria-associated spondylodiscitis.

Case presentation

A 79-year-old male presents with acute-on-chronic back pain in the absence of risk factors or exposures, aside from age. On radiological imaging, spondylodiscitis of L3-L4 was diagnosed. Subsequently, a CT-guided biopsy was performed to aid in confirming microbiological aetiology. Listeria monocytogenes was grown in culture and patient received appropriate antibacterial therapy.

Conclusion

The case highlights the utility of image-guided tissue sampling in aiding diagnosis and management in patients with vertebral osteomyelitis. It also encourages consideration of uncommon organisms such as Listeria as an etiology of vertebral osteomyelitis, even in the absence of prosthetic implants.
New oral spherical carbon adsorbent effectively reduces serum indoxyl sulfate levels in moderate to advanced chronic kidney disease patients: a multicenter, prospective, open-label study
Authors: Kim Seok-hyung , Jhee Jong Hyun , Choi Hoon Young , Lee Sang-Ho , Shin Sug Kyun , Lee So-Young , Yang Dong Ho , Yi Joo-Hark , Han Sang-Woong , Jo Young-Il , Park Hyeong Cheon
Published: July 2020

Background

Elevated levels of serum indoxyl sulfate (IS) have been linked to cardiovascular complications in patients with chronic kidney disease (CKD). Oral sorbent therapy using spherical carbons selectively attenuates IS accumulation in CKD patients. This study aimed to investigate whether oral administration of a new oral spherical carbon adsorbent (OSCA), reduces serum IS levels in moderate to severe CKD patients.

Methods

This prospective, multicenter, open-label study enrolled patients with CKD stages 3–5. Patients were prescribed OSCA for 8 weeks (6 g daily in 3 doses) in addition to standard management. Serum IS levels were measured at baseline and 4 and 8 weeks of treatment with OSCA.

Results

A total of 118 patients were enrolled and 87 eligible patients completed 8 weeks of study. The mean age of the study subjects was 62.8 ± 13.7 years, and 80.5% were male. Baseline levels of serum IS were negatively correlated with estimated glomerular filtration rate (eGFR) (r = − 0.406, P < 0.001) and increased with increasing CKD stages (stage 3, 0.21 ± 0.21 mg/dL; stage 4, 0.54 ± 0.52 mg/dL; stage 5, 1.15 ± 054 mg/dL; P for trend = 0.001). The patients showed significant reduction in serum total IS levels as early as 4 weeks after OSCA treatment (22.5 ± 13.9% reduction from baseline, P < 0.001) and up to 8 weeks (31.9 ± 33.7% reduction from baseline, P < 0.001). This reduction effect was noted regardless of age, kidney function, or diabetes. No severe adverse effects were reported. Gastrointestinal symptoms were the most commonly reported adverse effects. In total, 21 patients withdrew from the study, with dyspepsia due to heavy pill burden as the most common reason. The medication compliance rate was 84.7 ± 21.2% (min 9%, max 101%) for 8 weeks among those who completed the study.

Conclusions

OSCA effectively reduced serum IS levels in moderate to severe CKD patients. Gastrointestinal symptoms were the most commonly reported complications, but no treatment-related severe adverse effects were reported.

Trial registration

Clinical Research Information Service (KCT0001875. 14 December 2015.)
Rates, predictors, and mortality of sepsis-associated acute kidney injury: a systematic review and meta-analysis
Authors: Liu Jiefeng , Xie Hebin , Ye Ziwei , Li Fen , Wang Lesan
Published: July 2020

Background

Due to the high incidence and mortality of sepsis-associated acute kidney injury, a significant number of studies have explored the causes of sepsis-associated acute kidney injury (AKI). However, the opinions on relevant predictive risk factors remain inconclusive. This study aimed to provide a systematic review and meta-analysis to determine the predisposing factors for sepsis-associated AKI.

Method

A systematic literature search was performed in the Medline, Embase, Cochrane Library, PubMed, and Web of Science, databases, with an end-date of 25th May 2019. Valid data were retrieved in compliance with specific inclusion and exclusion criteria.

Result

Forty-seven observational studies were included for analysis, achieving a cumulative patient number of 55,911. The highest incidence of AKI was caused by septic shock. Thirty-one potential risk factors were included in the meta-analysis. Analysis showed that 20 factors were statistically significant. The odds ratio (OR) and 95% confidence interval (CI), as well as the prevalence of the most frequently-seen predisposing factors for sepsis-associated AKI, were as follows: septic shock [2.88 (2.36–3.52), 60.47%], hypertension [1.43 (1.20–1.70), 38.39%], diabetes mellitus [1.59 (1.47–1.71), 27.57%], abdominal infection [1.44 (1.32–1.58), 30.87%], the administration of vasopressors [2.95 (1.67–5.22), 64.61%], the administration of vasoactive drugs [3.85 (1.89–7.87), 63.22%], mechanical ventilation [1.64 (1.24–2.16), 68.00%], positive results from blood culture [1.60 (1.35–1.89), 41.19%], and a history of smoking [1.60 (1.09–2.36), 43.09%]. Other risk factors included cardiovascular diseases, coronary artery diseases, liver diseases, unknown infections, the administration of diuretics and ACEI/ARB, the infection caused by gram-negative bacteria, and organ transplantation.

Conclusion

Risk factors of S-AKI arise from a wide range of sources, making it difficult to predict and prevent this condition. Comorbidities, and certain drugs, are the main risk factors for S-AKI. Our review can provide guidance on the application of interventions to reduce the risks associated with sepsis-associated acute kidney injury and can also be used to tailor patient-specific treatment plans and management strategies in clinical practice.
Medium- and long-term effects of endovascular treatments for severely stenotic basilar arteries supported by multimodal imaging
Authors: Li Yuanzhi , Li Zhenfa , Song Ligang , Xie Weimin , Gong Xianghao , He Dongliang , Zhang Xin
Published: July 2020

Background

To evaluate the medium-and long-term effect of intravascular interventional therapy for symptomatic severe basilar artery stenosis supported by multimodal imaging.

Method

After strict screening of 67 patients with symptomatic severe basilar artery stenosis (70–99%) with atherosclerotic stenosis, 67 patients with symptomatic recurrence after intensive drug treatment were treated with intravascular balloon dilatation and Enterprise stent implantation. Any stroke or death within 30 days after operation and any stroke and restenosis during medium-and long-term follow-up were recorded.

Results

①The mean age of 67 patients (67lesions) was 57 ± 8 years old, and the technical success rate was 100%; ②Preoperative angiography showed that the collateral circulation was poor, and TICI was 1-2a while postoperative angiography showed that TICI was significantly improved to 2b-3; ③The average preoperative stenosis rate was 82 ± 9%, and the postoperative stenosis rate was reduced to 17 ± 10%; ④Before surgery, abnormal perfusion was found in the posterior circulation CTP; After the postoperative re-examination, the posterior circulation of CTP perfusion was significantly improved; ⑤Postoperative symptoms and neurological conditions improved significantly; ⑥Complications of perforating branch event occurred in 1 case after operation, and symptoms were relieved after more than 1 month of medication treatment, and mild neurological dysfunction remained. 1 case developed subacute thrombosis in the stent, which improved after active intra-arterial thrombolysis, and there was no residual neurological dysfunction; and 1 case of micro-guide wire being trapped by the distal vasospasm. ⑦67 patients were followed up by telephone, WeChat or imaging for 36–66 months.

Conclusions

In summary intravascular balloon dilation + Enterprise stent implantation is safe and effective for the treatment of symptomatic severe atherosclerotic stenosis of the basilar artery, with high technical success rate, low perioperative complications, and good mid-term and long-term effects.
Identifying women giving birth preterm and care at the time of birth: a prospective audit of births at six hospitals in India, Kenya, Pakistan and Uganda
Authors: Mitchell Eleanor J. , Benjamin Santosh , Ononge Sam , Ditai James , Qureshi Zahida , Masood Shabeen Naz , Whitham Diane , Godolphin Peter J. , Duley Lelia ,   on behalf of the “iCord Collaborative Group”, Whitham Diane , Mitchell Eleanor J. , Godolphin Peter J. , Duley Lelia , Benjamin Santosh , Mathews Jiji , Kumar Manish , Kuruvilla K. Anil , Nirmala M. , John Nayana , Ononge Sam , Nabwire Mariam , Byenkya Rose Mary , Nakinja Emilly , Ariokot Grace Engeu , Namuddu Sarah , Ditai James , Waiswa Stephen , Mudoola Macreen , Proscovia Auma , Abesco Julian , Magoba Susan , Qureshi Zahida , Osoti Alfred , Musoke Rachel , Mukhwana Raheli , Masood Shabeen Naz , Naqvi Zehra , Hashmi Haleema A. , Shamim Samina , Zaidi Syed Kashif Abbas , Masood Yasir
Published: July 2020

Background

Globally, 15 million infants are born preterm each year, and 1 million die due to complications of prematurity. Over 60% of preterm births occur in Sub-Saharan Africa and south Asia. Care at birth for premature infants may be critical for survival and long term outcome. We conducted a prospective audit to assess whether women giving birth preterm could be identified, and to describe cord clamping and neonatal care at hospitals in Africa and south Asia.

Methods

This prospective audit of livebirths was conducted at six hospitals in Uganda, Kenya, India and Pakistan. Births were considered preterm if between 28+ 0 and 33+ 6 weeks gestation and/or the birthweight was 1.00 to 1.99 kg. A pre-specified audit plan was agreed with each hospital. Livebirths before 28 weeks gestation with birthweight less than 1.0 kg were excluded. Data were collected on estimated and actual gestation and birthweight, cord clamping, and neonatal care.

Results

Of 4149 women who gave birth during the audit, data were available for 3687 (90%). As 107 were multiple births, 3781 livebirths were included, of which 257 (7%) were preterm. Antenatal assessment correctly identified 148 infants as ‘preterm’ and 3429 as ‘term’, giving a positive predictive value of 72% and negative predictive value of 97%. For term births, cord clamping was usually later at the two Ugandan hospitals, median time to clamping 50 and 76 s, compared with 23 at Kenyatta (Kenya), 7 at CMC (India) and 12 at FBH/LNH (Pakistan). At the latter two, timing was similar between term and preterm births, and between vaginal and Caesarean births. For all the hospitals, the cord was clamped quickly at Caesarean births, with Mbale (Uganda) having the highest median time to clamping (15 s ‘term’, 19 ‘preterm’). For preterm infants temperature on admission to the neonatal unit was below 35.5 °C for 50%, and 59 (23%) died before hospital discharge.

Conclusions

Antenatal identification of preterm birth was good. Timing of cord clamping varied between hospitals, although at each there was no difference between ‘term’ and ‘preterm’ births. For premature infants hypothermia was common, and mortality before hospital discharge was high.
Rare osteosarcoma cell subpopulation protein array and profiling using imaging mass cytometry and bioinformatics analysis
Authors: Batth Izhar S. , Meng Qing , Wang Qi , Torres Keila E. , Burks Jared , Wang Jing , Gorlick Richard , Li Shulin
Published: July 2020

Background

Single rare cell characterization represents a new scientific front in personalized therapy. Imaging mass cytometry (IMC) may be able to address all these questions by combining the power of MS-CyTOF and microscopy.

Methods

We have investigated this IMC method using < 100 to up to 1000 cells from human sarcoma tumor cell lines by incorporating bioinformatics-based t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis of highly multiplexed IMC imaging data. We tested this process on osteosarcoma cell lines TC71, OHS as well as osteosarcoma patient-derived xenograft (PDX) cell lines M31, M36, and M60. We also validated our analysis using sarcoma patient-derived CTCs.

Results

We successfully identified heterogeneity within individual tumor cell lines, the same PDX cells, and the CTCs from the same patient by detecting multiple protein targets and protein localization. Overall, these data reveal that our t-SNE-based approach can not only identify rare cells within the same cell line or cell population, but also discriminate amongst varied groups to detect similarities and differences.

Conclusions

This method helps us make greater inroads towards generating patient-specific CTC fingerprinting that could provide an accurate tumor status from a minimally-invasive liquid biopsy.
Novel mutation identified in Leber congenital amaurosis - a case report
Authors: Sato Shigeru , Morimoto Takeshi , Tanaka Sayaka , Hotta Kikuko , Fujikado Takashi , Tsujikawa Motokazu , Nishida Kohji
Published: July 2020

Background

Leber congenital amaurosis (LCA) is the earliest onset and the most severe form of all inherited retinal degenerative disorders, characterized by blindness, or severe visual impairment from birth, and typically exhibits clinical and genetic heterogeneity. Recently, 14 causative genes of LCA were reported. We performed whole-exome sequencing (WES) for Japanese siblings, and identified a novel homozygous nonsense mutation in the RPGR-interacting protein 1 (RPGRIP1) gene. We also report their follow-up data over 27 years.

Case presentation

Patient 1 is a 37-year-old male. In 1992, his eye position indicated orthophoria, however, horizontal nystagmus was evident, and he complained of photophobia. His best corrected decimal visual acuity (BCVA) was 0.2 (S + 6.5/C-3.5/170°) OD and 0.1 (S + 6.0/C-2.5/10°) OS. Fundus examination revealed bisymmetrical inferior focal retinal pigment epithelium (RPE) mottling. Bright-flash electroretinogram (ERG) revealed a subnormal pattern, while 30 Hz flicker ERG was non-recordable in both eyes. At his final visit in 2019, his BCVA was 0.09 (S + 3.5/C-3.5/180°) OD and 0.09 (S + 3.0/C-4.0/10°) OS. Patient 2, a 34-year-old female, is the sibling of patient 1. In 1992, her BCVA was 0.05 (S + 6.0) OD and 0.06 (S + 5.0) OS. She was in a chin-up position during visual acuity testing. Horizontal nystagmus was evident, and she also complained of photophobia. Bright-flash ERG was severely attenuated, and 30 Hz flicker ERG was non-recordable in both eyes. At her final visit in 2019, her BCVA was 0.02 (uncorrectable) OD and 0.03 (uncorrectable) OS. There were no other patients with LCA in their family and their parents were non-consanguineous. WES revealed a homozygous, consecutive, two-nucleotide variation in the RPGRIP1 gene (NM_020366: exon15:c.G2294A and c.C2295A, p.C765X), resulting in a premature stop codon. We interpreted this variation as a novel pathogenic mutation of RPGRIP1 that contributes to LCA6 development.

Conclusions

Herein, we report a novel nonsense mutation of RPGRIP1 in two patients with LCA6 and present their long-term follow-up data. These clinical data linked to genotypes provide important information for the development of new treatments, such as gene therapy, as well as for genetic counseling.
Identifying mechanisms of change in a magic-themed hand-arm bimanual intensive therapy programme for children with unilateral spastic cerebral palsy: a qualitative study using behaviour change theory
Authors: Fancourt Daisy , Wee Jaeyoung , Lorencatto Fabianna
Published: July 2020

Background

There has been much research into how to promote upper-limb skills to achieve functional independence in children with unilateral spastic cerebral palsy (USCP). One researched intervention is the Breathe Magic programme, which follows the protocol of hand-arm bimanual intensive therapy (HABIT) whilst, incorporating magic tricks to develop children’s motor skills and bimanual skills. However, whilst research has found the programme to be effective, there has been little consideration of how the intervention leads to a positive outcome: what the psychological, social and physical mechanisms of action are.

Methods

Qualitative semi-structured interviews with 21 children with USCP who participated in the Breathe Magic HABIT intervention, and focus groups with 17 parents and/or carers were undertaken. Analysis was conducted through the lens of the COM-B behaviour change model using a combined deductive framework and inductive thematic analysis. Reliability of coding was confirmed through random extraction and double coding of a portion of responses and the calculation of inter-rater reliability.

Results

Breathe Magic brings about change and positive outcomes by increasing children’s psychological and physical capabilities, providing social opportunities, and enhancing reflective and automatic motivation. Additionally, a number of enablers to engaging in the intervention were identified, particularly under psychological capabilities, social opportunities and both reflective and automatic motivation. Very few barriers were raised; those that were raised were of relatively low frequency of reporting.

Conclusions

By conducting a theory-based qualitative process evaluation, this study demonstrated the mechanisms of change behind the Breathe Magic HABIT intervention for children with USCP. Breathe Magic was found to be a well-structured combination of intended and unintended mechanisms of change. Overall, the success of Breathe Magic was observed through not only its intended mechanisms to enhance hand skills, but also through unintended psychological improvements in children’s hand function, as well as social and motivational benefits resulting from interaction between children and parents.