bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of biological sex on cryptococcal meningitis mortality in Uganda and South Africa
Authors: Stadelman Anna M , Ssebambulidde Kenneth , Tugume Lillian , Pastick Katelyn A , Hullsiek Kathy Huppler , Lofgren Sarah , Nuwagira Edwin , Evans Emily E , Williams Darlisha A , Muzoora Conrad , Meya David B , Rajasingham Radha , Rhein Joshua , Boulware David R
Published: December 2020

The role of biological sex on clinical outcomes and the pathogenesis of AIDS-related opportunistic infections is unknown. We assessed baseline biomarkers and outcomes between 577 men and 400 women in HIV-related cryptococcal meningitis cohorts in Uganda and South Africa from 2010 to 2017. We compared 10-week mortality by sex via Cox proportional hazards models. The 10-week mortality for women was 50% (198/400) and 43% (247/577) for men. Women had higher risk of death in an unadjusted model (Hazard Ratio (HR) = 1.20; 95%CI, 1.00–1.45; P = .05). Women maintained a higher risk when adjusting for quantitative CSF culture, altered mental status, CSF pleocytosis, age, and antiretroviral status (HR = 1.31; 95%CI, 1.07–1.59; P < .01). However, after adjusting for hemoglobin, the risk of death did not differ between women and men (HR = 1.17; 95%CI, 0.94–1.45; P = .17). Moderate to severe anemia (hemoglobin < 8.5 g/dL) was present among 16% (55/355) of women and 10% (55/532) of men (P = .02). Of the 373 participants with CSF biomarkers, men had higher median pro- and anti-inflammatory, monocyte/macrophage differentiation, maturation, and migration, immune exhaustion, and cytotoxicity cytokines than women (P < .05). We identified biological sex as proxy for anemia, a potentially modifiable risk factor for cryptococcal meningitis mortality. Immune response may contribute to the multifaceted underlying mechanisms for the discrepancy in mortality based on sex.

Lay Summary

We examined the role of biological sex in cryptococcal meningitis mortality in a large cohort. Our findings reveal significant differences in inflammatory markers by biological sex. Women have significantly higher mortality due to cryptococcal meningitis that is attributable to anemia at baseline.
Starspot evolution, differential rotation, and correlation between chromospheric and photospheric activities on Kepler-411
Authors: Xu Fukun , Gu Shenghong , Ioannidis Panogiotis
Published: December 2020

We present an analysis of the starspot evolution, the surface differential rotation (SDR), the correlation between chromospheric activity indicators and the spatial connection between chromospheric and photospheric activities on the active star Kepler-411, using time-series photometry over four years from Kepler, and spectroscopic data from Keck I 10-m and Lijiang 2.4-m telescopes. We constructed the light curve (LC) by re-performing photometry and reduction from the Target Pixel Files and Cotrending Basis Vectors with a manually redefined aperture using the software pyke3. An efficient program, gemc_lcm, was developed to apply a two-spots model to chosen LC segments with three spot groups at fixed latitudes (30○, 45○), (30○, 60○) and (45○, 60○). We found a periodic variation of the starspots at the period of about 660 d which independs on spot latitudes, and estimated the lower limit of SDR rate α = 0.1016(0.0023) and equatoral rotation period Peq = 9.7810(0.0169) d. Simultaneously, the relative variations of chromospheric activity indicators were derived by subtracting the overall mean spectrum from individual spectrum. It is found that Ca ii H and K emissions are strongly correlated with each other, and there also exists a correlation between Hα and Ca ii H & K emissions, with large dispersion, in accordance with previous results. Furthermore, we find the correlation between Ca ii H and K emissions is different in 2011 and 2012. The chromospheric emission variation shows a highly spatial anticorrelation with the LC, suggesting a spatial connection between the chromospheric active region and spot region.
Shock-powered radio precursors of neutron star mergers from accelerating relativistic binary winds
Authors: Sridhar Navin , Zrake Jonathan , Metzger Brian D , Sironi Lorenzo , Giannios Dimitrios
Published: December 2020

During the final stages of a compact object merger, if at least one of the binary components is a magnetized neutron star (NS), then its orbital motion substantially expands the NS’s open magnetic flux – and hence increases its wind luminosity – relative to that of an isolated pulsar. As the binary orbit shrinks due to gravitational radiation, the power and speed of this binary-induced inspiral wind may (depending on pair loading) secularly increase, leading to self-interaction and internal shocks in the outflow beyond the binary orbit. The magnetized forward shock can generate coherent radio emission via the synchrotron maser process, resulting in an observable radio precursor to binary NS merger. We perform 1D relativistic hydrodynamical simulations of shock interaction in the accelerating binary NS wind, assuming that the inspiral wind efficiently converts its Poynting flux into bulk kinetic energy prior to the shock radius. This is combined with the shock maser spectrum from particle-in-cell simulations, to generate synthetic radio light curves. The precursor burst with a fluence of ∼1 Jy·ms at ∼GHz frequencies lasts ∼1–500 ms following the merger for a source at ∼3 Gpc (Bd/1012 G)8/9, where Bd is the dipole field strength of the more strongly magnetized star. Given an outflow geometry concentrated along the binary equatorial plane, the signal may be preferentially observable for high-inclination systems, that is, those least likely to produce a detectable gamma-ray burst.
Angular power spectrum of supernova remnants: effects of structure, geometry and diffuse foreground
Authors: Choudhuri Samir , Saha Preetha , Roy Nirupam , Bharadwaj Somnath , Dey Jyotirmoy
Published: December 2020

The study of the intensity fluctuation power spectrum of individual supernova remnants (SNRs) can reveal the structures present at sub-pc scales, and also constrain the physical process that generates those structures. There are various effects, such as the remnant shell thickness, projection of a three-dimensional structure onto a two-dimensional observational plane, and the presence of diffuse “foreground” emission, which causes the observed power spectrum to deviate from the intrinsic power spectrum of the fluctuations. Here, we report results from a systematic study of these effects, using direct numerical simulations, in the measured power spectrum. For an input power-law power spectrum, independent of the power-law index, we see a break in the observed power law at a scale which depends on the shell thickness of a shell-type SNR, and the three-dimensional turbulence changes to two-dimensional turbulence beyond that scale. We also report how the estimated power spectrum is expected to deviate from the intrinsic SNR power spectrum in the presence of additional diffuse Galactic synchrotron emission (DGSE) around the remnant shell. For a reasonable choice of the parameters, if the intrinsic SNR power spectrum is shallower than the DGSE power spectrum, the SNR contribution dominates at small angular scales of the estimated power spectra. On the other hand, if the SNR power spectrum is relatively steeper, the original power spectra is recovered only over a small window of angular scales. This study shows how detailed modeling may be used to infer the true power spectrum from the observed SNR intensity fluctuations power spectrum, which in turn can be used to constrain the nature of the turbulence that gives rise to these small scale structures.
Regional inequalities and contributions to aggregate growth in the 2000s: an EU vs US comparison based on functional regions
Authors: Garcilazo Enrique , Moreno-Monroy Ana I , Oliveira Martins Joaquim
Published: December 2020

This paper offers a comparative analysis of regions in the United States (US) and European Union (EU) countries before and during the aftermath of the global financial crisis. By using a regional taxonomy approaching a functional definition, we can compare in a more meaningful way the regions in EU countries and the US. We use of a newly developed OECD functional typology of TL3 (Territorial Level 3) regions, which classifies regions into five categories: two are metropolitan regions (with a very large or large city) and three are regions with accessibility to cities of different sizes. Over the period 2000–17, we assess which types of regions have been most resilient or vulnerable to the effects of the crisis. To identify structural factors, we analyse the evolution of the contributions of regions to aggregate GDP and productivity growth. Some structural patterns emerge, which are then related to the evolution of regional inequalities between 2000 and 2017. Overall, we found that regional inequalities seem mainly related to structural factors rather than macroeconomic shocks, such as the global financial crisis.
Domestic violence detection amid the COVID-19 pandemic: the value of the WHO questionnaire in emergency medicine
Authors: Di Franco M , Martines G F , Carpinteri G , Trovato G , Catalano D
Published: December 2020

Background

Gender-based violence affects 35–45% of women worldwide, mostly coming from domestic violence. A good screening procedure in clinical practice is useful, but WHO does not advise universal screening, recommending further research.

Aim

(i) To report the frequency of domestic violence cases among admissions to the Emergency Room of a major Italian Hospital in 2020, including during complete ‘Lockdown’ period; (ii) to document acute and chronic health effects of domestic violence and (iii) to asses usefulness of the WHO screening as a tool for uncovering cases which would otherwise remain hidden.

Design and methods

A database containing all the information recorded for each of 19 160 patients in the Emergency Room was constructed by a keyword search (‘violence’, ‘assault’, ‘trauma’) to filter the data and retrieve cases of violence in the period between 1 January and 2 June 2020. The self-administered questionnaire of the WHO Multi-country Study on Women’s Health and Domestic Violence against Women was used in women referred to the emergency room for any cause, excluding trauma.

Results

A recent history of domestic violence was disclosed by 22.67%, after completing the WHO questionnaire. Of those not participating in the survey, diagnosis of domestic violence was only 0.6% (128/19 160).

Conclusion

Power of detection of domestic violence by the WHO questionnaire is very high, while the frequency of occurrence of these events in this population was considerable. Seemingly, it elicits the responsiveness to the topic of the volunteer interviewees. Its use should be firmly recommended, reasonably, while Covid-19 pandemic is affecting health, rights and response.
Home Equity and Labor Income: The Role of Constrained Mobility
Authors: Gopalan Radhakrishnan , Hamilton Barton H , Kalda Ankit , Sovich David
Published: December 2020

Using detailed data for U.S. homeowners, we document a negative, nonlinear relation between the loan-to-value ratio (LTV) of homeowners’ primary residence and their labor income. Consistent with high LTV individuals experiencing constrained mobility, we find stronger effects among subprime, liquidity- constrained individuals and those living in regions with limited alternative local employment opportunities and strict noncompete law enforcement. Though high LTV individuals are less likely to move across MSAs, they are more likely to change jobs without changing their residence. We find no effects among similar neighboring renters employed at the same firm and with a similar job tenure.
Low molecular weight-PAHs induced inflammation in A549 cells by activating PI3K/AKT and NF-κB signaling pathways
Authors: Guo Huizhen , Huang Yushan , Wang Huiling , Zhang Zhewen , Li Chengyun , Hu Fengjing , Zhang Wenwen , Liu Yang , Zeng Yong , Wang Junling
Published: December 2020

Our previous study has demonstrated that two low molecular weight-polycyclic aromatic hydrocarbons (LMW-PAHs), phenanthrene (Phe) and fluorene (Flu), alone and as a mixture could induce oxidative damage and inflammation in A549 cells. However, the associated mechanisms have not been well discussed. The aim of this study was to further investigate the roles of PI3K/AKT and NF-κB signaling pathways in the inflammatory effects in A549 cells induced by Phe, Flu and their mixture. The results indicated that Phe, Flu and their mixture significantly activated PI3K/AKT and NF-κB signaling pathways by increasing the phosphorylation levels of PI3K, AKT, IκBα and NF-κB p65. In addition, pro-inflammatory cytokine expressions of TNF-α and IL-6 induced by the binary mixture of Phe and Flu were all alleviated by co-treatment with PI3K/AKT and NF-κB specific inhibitors (LY294002 and BAY11-7082). The results suggested that PI3K/AKT and NF-κB signaling pathways played an important role in LMW-PAHs induced inflammation in A549 cells.
Pleurostoma Decline of Olive Trees Caused byPleurostoma richardsiaein California
Authors: Lawrence Daniel P. , Nouri Mohamed T. , Trouillas Florent P.
Published: December 2020

A single fungal pathogen was consistently isolated from symptomatic wood of olive trees (Olea europaea) displaying branch and trunk cankers in superhigh-density orchards in the Sacramento and San Joaquin Valleys of California. Morphological characters of the pathogen included two distinct types of conidia (thick-walled, dark brown, and globose and thin-walled, hyaline, and oblong to ellipsoid) and three types of phialides, indicating a pleurostoma-like fungus. Phylogenetic results of four nuclear loci including the internal transcribed spacer (ITS) region (ITS1-5.8S-ITS2) and partial sequences of the actin, beta-tubulin, and translation elongation factor 1-α genes confirmed the isolates as Pleurostoma richardsiae. Pathogenicity trials conducted in the field involving 2- to 3-year-old branches of three widely planted oil olive cultivars (Arbequina, Arbosana, and Koroneiki) satisfied Koch’s postulates and confirmed the pathogenic nature of this species to cause the decline of olive trees in California. All three cultivars were equally susceptible to Pl. richardsiae, indicating no detectable resistance to the pathogen. Additional isolations from symptomatic hosts including almond, peach, pistachio, and plum, also confirmed this species, suggesting that Pl. richardsiae is widespread in agricultural systems and should be considered an emerging pathogen of fruit and nut crops in California.
Identification and Description of a New Pathogen Causing Flower Dry Rot on Passiflora edulis in China
Authors: Liu Yuelian , Tang Jianrong , Zhou Yuhan
Published: December 2020

Passiflora edulis Sims (passion fruit) is an economically important fruit crop. However, a new flower dry rot has occurred in orchards located in Zhanjiang, China, and has led to serious production loss. Its disease incidence is approximately 30 to 40%. A total of 221 isolates of Fusarium sp. were obtained from samples of three types of symptomatic flowers. Three representative single-spore isolates (PaB-1, PaB-2, and PaB-3) from each type were used for pathogenicity tests, multilocus phylogenetic analyses, and morphological descriptions. Pathogenicity tests of buds of 5-month-old P. edulis plants showed symptoms similar to those observed in nature, and Koch’s postulates were achieved. By comparing 36 typical species from the FUSARIUM-ID database, multilocus phylogenetic analyses showed that the sequences of TEF1, RPB2, and ITS of these isolates belong to the Incarnatum clade of the F. incarnatum–equiseti species complex (FIESC-17-a) with an independent branch. Therefore, the pathogenic isolates were identified as F. pernambucanum (FIESC-17-a). Moreover, in this study, the conidial anastomosis tubes were first observed in the FIESC. This is the first report of flower dry rot on P. edulis caused by F. pernambucanum. Further studies should be performed to determine effective disease management strategies.
Patients With High Chronic Postoperative Knee Pain 5 Years After Total Knee Replacement Demonstrate Low-grad Inflammation, Impairment of Function, and High Levels of Pain Catastrophizing
Authors: Skrejborg Peter , Petersen Kristian K. , Kold Søren , Kappel Andreas , Pedersen Christian , Østgaard Svend E. , Simonsen Ole , Arendt-Nielsen Lars
Published: December 2020

Objectives:

Total knee replacement (TKR) normally provides improvements of physical function and reduces pain. However, ∼20% of the patients report chronic postoperative knee pain. The aims of the present study were to assess the pain, physical function, and physiological characteristics 5 years after TKR surgery.

Materials and Methods:

Eighty patients were recruited 5 years after TKR and divided into 2 groups based on their average 24-hour knee pain intensity assessed on a visual analog scale (VAS 0 to 10) (“high pain group”: VAS≥3; “low pain group”: VAS<3). The patients completed the PainDETECT Questionnaire (PDQ), Oxford Knee Score (OKS), Pain Catastrophizing Scale, and Forgotten Joint Score-12. Furthermore, the patients underwent a clinical examination of the knees and high-sensitivity serum C-reactive protein was measured as an inflammatory marker.

Results:

A total of 53% of the patients in the high pain group were not satisfied with the outcome, while only 11% of the patients in the low pain group was not satisfied, and the pain intensities in the 2 groups were 5.1 (4.6 to 5 to 6) and 1.1 (0.6 to 1.5) (P<0.001), respectively. Furthermore, the high pain group demonstrates worse scores in: Forgotten Joint Score-12 (P=0.001), OKS function (P<0.001), OKS pain (P<0.001), and Pain Catastrophizing Scale (P<0.001).

The high pain group demonstrated increased level of high-sensitivity serum C-reactive protein (4.3 mg/L [3.2 to 5.5] vs. 1.7 mg/L [1.2 to 2.2], P<0.001), and decreased range of motion in the knee (110 vs. 119-degree range of motion, P=0.013).

Discussion:

Patients with high chronic postoperative knee pain 5 years after TKR demonstrate decreased physical function, higher levels of catastrophizing thoughts, and increased levels of inflammation.
The Minimum Clinically Important Difference for Patient Health Questionnaire-9 in Minimally Invasive Transforaminal Interbody Fusion
Authors: Lynch Conor P. , Cha Elliot D.K. , Jenkins Nathaniel W. , Parrish James M. , Mohan Shruthi , Jadczak Caroline N. , Geoghegan Cara E. , Singh Kern
Published: December 2020

Study Design.

Retrospective cohort.

Objective.

To investigate and establish minimum clinically important differences (MCID) for Patient Health Questionnaire-9 (PHQ-9) among patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS TLIF).

Summary of Background.

Spine surgery is linked to postoperative improvements in anxiety, depression, and mental health. These improvements have been documented using patient-reported outcome measures such as PHQ-9. Few studies evaluated the clinical significance of PHQ-9 for lumbar spine surgery.

Methods.

Patients who underwent single-level, primary MIS TLIF from 2015 to 2017 were retrospectively reviewed in a prospective database. Patients with incomplete preoperative and 2-year postoperative PHQ-9 surveys were excluded. Demographic and perioperative characteristics were recorded. PHQ-9, 12-Item Short Form (SF-12), and Veterans RAND 12-Item Health Survey (VR-12) Mental Component Summary (MCS) were collected at preoperative, 6-week, 12-week, 6-month, 1-year, and 2-year intervals. MCID was calculated using anchor and distribution-based methods. SF-12 served as an anchor. MCID was assessed using mean change methodology, four receiver operating characteristic curve assessments, and standard error measurement. Cutoff values were selected from receiver operating characteristic curve analysis. MCID achievement rates for all patient-reported outcome measures were calculated.

Results.

A total of 139 patients met inclusion criteria, with a mean age of 55 years and 39% females. The most common spinal pathology was radiculopathy (92%). MCID analysis revealed the following ranges of values: 2.0 to 4.8 (PHQ-9), 6.7 to 12.1 (SF-12 MCS), and 7.5 to 15.9 (VR-12 MCS). Final MCID thresholds were 3.0 (PHQ-9), 9.1 (SF-12 MCS), and 8.1 (VR-12 MCS). MCID achievement at 2-years for PHQ-9, SF-12 MCS, and VR-12 MCS was 89.2%, 85.6%, and 84.9% respectively.

Conclusion.

Our 2-year postoperative MCID analysis is the first mental health calculation from an MIS TLIF cohort. We report a 2-year MCID value for PHQ-9 of 3.0 (2.0–4.8). MCID values for mental health instruments are important for determining overall success of lumbar spine surgery.

Level of Evidence: 3
In-hospital Course and Complications of Laminectomy Alone Versus Laminectomy Plus Instrumented Posterolateral Fusion for Lumbar Degenerative Spondylolisthesis
Authors: Badhiwala Jetan H. , Leung Sean N. , Jiang Fan , Wilson Jamie R.F. , Akbar Muhammad A. , Nassiri Farshad , Witiw Christopher D. , Wilson Jefferson R. , Fehlings Michael G.
Published: December 2020

Study Design.

Retrospective analysis of data from the National Surgical Quality Improvement Program (NSQIP).

Objective.

We sought to compare the short-term outcomes of laminectomy with/without fusion for single-level lumbar degenerative spondylolisthesis (DS).

Summary of Background Data.

Lumbar DS is a common cause of low back and radicular pain. Controversy remains over the safety and efficacy of fusion in addition to standard decompressive surgery.

Methods.

Patients with lumbar DS who underwent laminectomy alone or laminectomy plus posterolateral fusion at a single level were identified from the 2012–2017 NSQIP database. Outcomes included 30-day mortality, major complication, reoperation, readmission, as well as operative duration, need for blood transfusion, length of stay (LOS), and discharge destination. Outcomes were compared between treatment groups by multivariable regression, adjusting for age, sex, and comorbidities (modified Frailty Index). Effect sizes were reported by adjusted odds ratio (aOR) or mean difference (aMD).

Results.

The study cohort consisted of 1804 patients; of these, 802 underwent laminectomy alone and 1002 laminectomy plus fusion. On both unadjusted and adjusted analyses, there was no difference in 30-day mortality, major complications, reoperation, or readmission. However, laminectomy plus fusion was associated with longer operative time (170.0 vs. 152.7 minutes; aMD 16.00 minutes, P < 0.001), longer hospital LOS (3.2 vs. 2.5 days; aMD 0.68, P < 0.001), more frequent need for intra- or postoperative blood transfusion (6.8% vs. 3.1%; aOR 2.24, P = 0.001), and less frequent discharge home (80.7% vs. 89.2%; aOR 0.46, P < 0.001).

Conclusion.

We found single-level laminectomy plus fusion for lumbar DS to have a comparable short-term safety profile to laminectomy alone. However, fusion was associated with longer operative time and LOS, higher risk of blood transfusion, and greater need for inpatient rehabilitation. These factors should be recognized by clinicians and discussed with patients in the context of their values when weighing surgical treatment of lumbar DS.

Level of Evidence: 3
Association of Duration of Preoperative Opioid Use with Reoperation After One-level Anterior Cervical Discectomy and Fusion in Nonmyelopathic Patients
Authors: Samuel Andre M. , Lovecchio Francis C. , Premkumar Ajay , Vaishnav Avani S. , Kim Han Jo , Qureshi Sheeraz A.
Published: December 2020

Study Design

Retrospective cohort study.

Objective

The aim of this study was to determine that rates of preoperative opioid use in patients undergoing single-level anterior discectomy and fusion (ACDF) without myelopathy and determine the association with reoperations over 5 years

Summary of Background Data

Preoperative opioid use before cervical spine surgery has been linked to worse postoperative outcomes. However, no studies have determined the association of duration and type of opioid used with reoperations after ACDF.

Methods

Patients undergoing single-level ACDF without myelopathy between 2007 and 2016 with at least 5-year follow-up were identified in one private insurance administrative database. Preoperative opiate use was divided into acute (within 3 months), subacute (acute use and use between 3 and 6 months), and chronic (subacute use and use before 6 months) and by the opiate medication prescribed (tramadol, oxycodone, and hydrocodone). Postoperative rates of additional cervical spine surgery were determined at 5 years and multivariate logistic regression was used to determine the association of preoperative opiates with additional surgery.

Results

Of 445 patients undergoing single-level ACDF without myelopathy, 66.3% were taking opioid medications before surgery. The most commonly used preoperative opioid was hydrocodone (50.3% acute use, 24.7% chronic use). Opioid-naïve patients had a 5-year reoperation rate of 4.7%, compared to 25.0%, 15.5%, and 23.3% with chronic preoperative use of tramadol, hydrocodone, and oxycodone. In multivariate analysis, controlling for age, sex, and Charlson Comorbidity Index, chronic use of hydrocodone (odds ratio [OR] = 2.08, P = 0.05), oxycodone (OR = 4.46, P < 0.01), and tramadol (OR = 4.01, P = 0.01) were all associated with increased reoperations. However, acute use of hydrocodone, oxycodone, and tramadol was not associated with reoperations (P > 0.05).

Conclusion

Both subacute and chronic use of common lower-dose opioid medications is associated with increased reoperations after single-level ACDF in nonmyelopathic patients. This information is critical when counseling patients preoperatively and developing preoperative opioid cessation programs.

Level of Evidence: 3
Effects of N-acetylcysteine treatment on ethanol’s rewarding properties and dopaminergic alterations in mesocorticolimbic and nigrostriatal pathways
Authors: Laverde Celina Ferrari , Morais-Silva Gessynger , Amaral Vanessa Cristiane Santana , Marin Marcelo Tadeu
Published: December 2020

Recent reports have shown that N-acetylcysteine (N-AC) has beneficial effects in the treatment of cocaine and nicotine abuse. Considering the similar neurobiologic mechanisms involved in the development of addiction to different drugs, N-AC treatment could be useful in the treatment of ethanol abuse. The rewarding properties of the drugs of abuse plays an important role in the development of addiction and can be studied using the conditioned place preference (CPP) paradigm. Thus, to study the effects of N-AC treatment in the rewarding effects of ethanol, we investigated the effects of N-AC administration in the ethanol-induced CPP and neurochemical alterations within the mesocorticolimbic and the nigrostriatal dopaminergic pathways. Adult male Swiss mice were pretreated with N-AC (60 or 120 mg/kg intraperitoneal) and tested for the development, expression, or extinction of the ethanol-induced CPP. Another cohort of animals received N-AC (60 or 120 mg/kg intraperitoneal) 2-h before an acute administration of ethanol and had their brains removed for dopamine and its metabolites quantification in the mesocorticolimbic and nigrostriatal pathways. Pretreatment with N-AC (120 mg/kg) blocked the development of ethanol-induced CPP. On the other hand, N-AC at both doses did not alter the expression nor the extinction of ethanol-induced CPP. N-AC increased 3,4-dihydroxyphenylacetic acid content in the medial prefrontal cortex and dopaminergic turnover within the substantia nigra. Besides that, there was an increase in dopamine content in the nucleus accumbens of ethanol-treated animals. In summary, N-AC treatment blocked the development of ethanol CPP, without altering ethanol effects on dopaminergic neurotransmission.
MASSIVE BILATERAL SEROUS RETINAL DETACHMENT IN A YOUNG PATIENT WITH HYPERTENSIVE CHORIORETINOPATHY AND CHRONIC KIDNEY DISEASE
Authors: Arévalo Simental Diana Esperanza , Sepulveda Tinajero Luis Humberto , Villarreal Contreras Fátima Andrea , Becerra Cota Miriam Guadalupe , Ingolotti Mariana
Published: December 2020

Purpose:

Report a case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment in a young patient with chronic kidney disease.

Methods:

Observational case report.

Results:

An 18-year-old man with Grade 5 chronic kidney disease, systemic high blood pressure, secondary acute pulmonary edema, and acute uremic syndrome was referred to our service complaining of bilateral decreased vision starting one week ago. The patient was treated at that moment with hemodialysis and losartan. At initial examination, the patient's blood pressure was 170/120 mmHg; dilated fundus examination evidenced optic disk edema, hypertensive chorioretinopathy, and massive serous retinal detachment with best-corrected visual acuity of hand motion in both eyes. The case was diagnosed as undertreated hypertension and was referred to the nephrologist for treatment adjustments. At 1-month follow-up, blood pressure was 160/90 mmHg; there was clinical improvement in both eyes but with ischemic sequelae. At the final follow-up 6 months later, blood pressure was 100/60 mmHg, best-corrected visual acuity was 20/80 in the right eye and count fingers at 2 min the left eye, and there was a complete resolution of the retinal serous detachment in both eyes.

Conclusion:

Patients with massive serous detachments due to systemic hypertension are atypical so it is of immense importance for the ophthalmologists to recognize the ocular manifestations of systemic diseases that put the patient's life at risk as in this case.
Anterior Segment Surgeries Under Topical Fresh Frozen Plasma Treatment in Ligneous Conjunctivitis
Authors: Ozbek-Uzman Selma , Yalniz-Akkaya Zuleyha , Nurozler Tabakci Burcu , Singar Evin , Burcu Ayse
Published: December 2020

Purpose:

To evaluate the efficacy of topical fresh frozen plasma (FFP) therapy on clinical symptoms, findings, and prognosis after anterior segment surgeries in patients with ligneous conjunctivitis (LC).

Methods:

Retrospective case note review.

Results:

Eleven eyes of 7 cases whose remission was not achieved after medical treatment such as topical corticosteroids, cyclosporine A, and heparin were included in the study. The median age of admission was 19 (1–49) years, median duration of FFP treatment was 48 (15–79) months, median follow-up period was 62 (16–114) months, and median age at symptom onset was 12 (4–252) months. Diagnosis was made according to clinical presentations, plasminogen activities, and response to treatment. Topical FFP that was prepared in our clinic was used in all cases. Surgeries (membrane excision, eyelid surgery, deep anterior lamellar keratoplasty, and cataract surgery) were performed after at least 1 month of FFP treatment. Prosthetic contact lens was applied to one eye. During the follow-up period, recurrences requiring membrane excision and side effects from topical FFP were not observed.

Conclusions:

LC is a rare membranous conjunctivitis that proceeds with remissions and recurrences. When it was shown that the etiology of LC is plasminogen deficiency, FFP became the only treatment option targeting the etiology. In this study, we observed that the topical FFP is an effective treatment method that prevents recurrence and ensures regression of membranes and safer anterior segment surgeries in LC.
Supply and Demand of Domestic Corneal Tissue and Its Implications on Export Potential—Using Australia as an Example
Authors: Machin Heather , Buckland Lisa , Georges Pierre , Ghabcha Mona , Golding-Holbrook Tamme , Leighton Candice , Mackey Adrienne , Weinel Luke , Whiting Victoria , Sutton Gerard , Baird Paul N.
Published: December 2020

Purpose:

Corneal tissue importation is only possible if another country is able to export corneas without impacting its own domestic demand. Currently, there is little evidence to indicate whether export nations have such surplus capacity and in a position to export. To explore this concept, we examined our nation, Australia, which is reported to routinely decline donations because of its ability to meet domestic corneal transplant demand. Our research offers insights and opportunities for Australia and other nations to evaluate their domestic and international supply and allocation of corneal tissue in this space.

Method:

We collated 12 months of data on collected and noncollected donations, through participating Australian Eye Banks. The explanation of why some known donors were declined or not pursued indicated if demand was met and potential surplus-for-export levels.

Results:

There were 7.5% (n = 11,889) of deaths in Australia that were notified to Australian Eye Banks during our reporting period. Of those, 9.3% (n = 1106/11,889) were recovered and allocated, 15.7% (n = 1863/11,889) were known but declined, and 75% (n = 8920/11,889) were not pursued. Of those that were declined, 64.3% (n = 1197/1863) were declined because of limitations with service/manpower at the eye bank, whereas 35.7% (n = 666/1863) were declined because demand was met.

Conclusions:

Australia did not meet demand all the time, during our data period. There were adequate quantities of potential donors to support increasing recovery for domestic allocation and provide for exportation without hindrance to Australian demand. Further examination of domestic supply and demand cycles and the export process is required before routine exportation.
Association between inter-arm difference in SBP and central blood pressure in a Beijing community cohort
Authors: Ma Wei , Qi Litong , Fan Fangfang , Yang Ying , Zhang Baowei , Jia Jia , Li Min , Zhang Yan , Huo Yong
Published: December 2020

Objective

The inter-arm SBP difference (IASBPD) can serve as a predictor of cardiovascular disease (CVD). In this study, we aimed to determine the relationship between IASBPD and central blood pressure (CBP).

Methods

The study cohort comprised of 7842 eligible individuals. Their BPs were assessed simultaneously in both arms using an Omron BP-203RPEIII vascular profiler, and the IASBPD was measured as the absolute difference in these values (absolute value of left minus right). The CBP was noninvasively measured using an Omron HEM-9000AI device. Multivariate regression analysis was used to assess the association between the central SBP (cSBP) and the IASBPD.

Results

An IASBPD of ≥10 mmHg was positively associated with the cSBP (β = 2.26; 95% confidence interval, 1.04–3.48; P < 0.001). The interaction test showed no significant interactions between the IASBPD and any of the assessed covariates (age group; sex; BMI; smoking status; heart rate group; the presence of hypertension, diabetes, or CVD; and antihypertensive drug use) when the cSBP was used as the outcome in the subgroup analysis.

Conclusion

The mechanism underlying the ability of the IASBPD to predict CVD may partly involve an increase in the CBP.
Diverse clinical outcome of Hunter syndrome in patients with chromosomal aberration encompassing entire and partial IDS deletions: what is important for early diagnosis and counseling?
Authors: Jezela-Stanek Aleksandra , Pokora Paulina , Młynek Marlena , Smyk Marta , Ziemkiewicz Kamila , Różdżyńska-Świątkowska Agnieszka , Tylki-Szymańska Anna
Published: December 2020

Our study aims to delineate the syndromology of Hunter syndrome (MPSII), by presenting three patients with different clinical courses, caused by different genetic mechanisms. Single-nucleotide variants (SNV) or small deletions encompassing the iduronate-2-sulfatase (IDS) gene are identified in the majority of affected individuals, while deletion of contiguous genes or whole IDS gene (described herein) has been reported rarely, mainly in patients with a severe Hunter syndrome presentation. There is; however, lack of reliable genotype–phenotype correlation, especially regarding anthropometric parameters, and thus our understanding of MPSII pathophysiology is not complete. On the basis of our observations, we would like to draw attention to the fact that neurological manifestations observed in patients with contiguous gene deletions, encompassing the IDS gene, may significantly differ from those observed in SNV. The phenotype is; however, difficult to predict and depends on the type (deletion/duplication), size (small/large) of aberration, and gene content. Moreover, it also has implications for genetic counseling, and recurrence risk in those families differs from the usual situation and must be clarified by parental chromosomal studies.
Timing of Cleft Palate Repair in Patients With and Without Robin Sequence
Authors: Skolnick Gary B. , Keller Matthew R. , Baughman Ethan J. , Nguyen Dennis C. , Nickel Katelin B. , Naidoo Sybill D. , Olsen Margaret A. , Patel Kamlesh B.
Published: December 2020

Background:

This cohort study aimed to assess how age at repair affects outcomes in nonsyndromic patients with and without Robin Sequence using a national database of commercial healthcare claims.

Methods:

Children under 4 years of age undergoing palatoplasty were identified in the IBM MarketScan Commercial Database based on ICD-9-CM and CPT procedure codes. They were divided into Robin and non-Robin cleft palate groups, and further divided by time of initial cleft palate repair: Robin Sequence into 2 groups: age ≤10 months or >10 months; non-Robin cleft palate into 3 groups: age ≤10 months, >10–14 months, or >14 months age. Time to cleft palate revision within each group was assessed using Cox proportional-hazard models.

Results:

A total of 261 patients with Robin Sequence and 3046 with non-Robin cleft palate were identified. In patients with Robin, later repair was associated with decreased risk of secondary procedures compared with early repair (Hazard Ratio (HR) 0.19, 95%CI 0.09–0.39, P < 0.001). In patients with non-Robin cleft palate, decreased risk of revision compared to early repair was associated both with repair at >10–14 months (adjusted HR 0.40, 95%CI 0.31–0.52, P < 0.001) and > 14 months (adjusted HR 0.71, 95%CI 0.57–0.88, P = 0.002). Adjusting for timing of repair, patients with non-Robin cleft palate were at significantly increased risk of secondary procedure if diagnosed with failure to thrive or anemia in the 30 days prior to palatoplasty.

Conclusions:

In patients with and without Robin sequence, cleft palate repair at or before 10 months of age was associated with higher risk for secondary procedures.
Reproducible breath metabolite changes in children with SARS-CoV-2 infection
Authors: Berna Amalia Z. , Akaho Elikplim H. , Harris Rebecca M. , Congdon Morgan , Korn Emilie , Neher Samuel , M’Farrej Mirna , Burns Julianne , John Audrey R. Odom
Published: December 2020

SARS-CoV-2 infection is diagnosed through detection of specific viral nucleic acid or antigens from respiratory samples. These techniques are relatively expensive, slow, and susceptible to false-negative results. A rapid non-invasive method to detect infection would be highly advantageous. Compelling evidence from canine biosensors and studies of adults with COVID-19 suggests that infection reproducibly alters human volatile organic compounds (VOCs) profiles. To determine whether pediatric infection is associated with VOC changes, we enrolled SARS-CoV-2-infected and -uninfected children admitted to a major pediatric academic medical center. Breath samples were collected from children and analyzed through state-of-the-art GCxGC-ToFMS. Isolated features included 84 targeted VOCs. Candidate biomarkers that were correlated with infection status were subsequently validated in a second, independent cohort of children. We thus find that six volatile organic compounds are significantly and reproducibly increased in the breath of SARS-CoV-2-infected children. Three aldehydes (octanal, nonanal, and heptanal) drew special attention, as aldehydes are also elevated in the breath of adults with COVID-19. Together, these biomarkers demonstrate high accuracy for distinguishing pediatric SARS-CoV-2 infection and support the ongoing development of novel breath-based diagnostics.
Sulodexide in the treatment of patients with early stages of COVID-19: a randomised controlled trial
Authors: Gonzalez-Ochoa Alejandro J. , Raffetto Joseph D. , Hernández Ana G. , Zavala Nestor , Gutiérrez Obed , Vargas Arturo , Loustaunau Jorge
Published: December 2020

Background

Targeting endothelial cells has been suggested for the treatment of patients with COVID-19 and sulodexide has pleiotropic properties within the vascular endothelium that can prove beneficial to the same. We aimed to evaluate the effect of sulodexide when used in the early clinical stages of COVID-19.

Methods

We conducted a single-centre, outpatient setting, randomised controlled trial with a parallel-group design in Mexico. Including patients within three days of clinical symptom onset, who were at a high risk of severe clinical progression due to chronic comorbidities. Participants were randomly allocated to receive an oral dose of sulodexide (500 LRU twice a day) or the placebo for 21 days. Primary outcomes were need and length of hospitalisation, need and length of oxygen support.

Results

Between June 5 and August 30, 2020, 243 patients were included in the “per-protocol” analysis. One hundred twenty-four of them received sulodexide, while 119 received placeboes. At 21 days follow-up, 22 of 124 patients required hospitalisation in the sulodexide group compared to 35 of 119 in the placebo group [relative risk (RR), 0·6; 95% confidence interval (CI), 0·37-0·96; p=0·03]. Fewer patients required oxygen support in the sulodexide group [37 of 124 vs. 50 of 119; RR, 0·71; 95% CI, 0·5 to 1; p=0·05], and for fewer days (9±7·2 in the sulodexide group vs. 11·5±9·6 in the placebo group; p=0·02). There was no between-group difference concerning the length of hospital stay.

Interpretation

Early intervention in COVID-19 patients with sulodexide reduced hospital admissions and oxygen support requirements, although with no significant effect on mortality. This has beneficial implications in the patient well-being, making sulodexide a favourable medication until an effective vaccine or an antiviral becomes available.

Funding

Researcher independently initiated, partially funded by Alfasigma, Mexico.

Listed in the ISRCTN registry under ID ISRCTN59048638.
The prognostic value of lymph node involvement after neoadjuvant chemotherapy is different among breast cancer subtypes
Authors: Laot Lucie , Laas Enora , Girard Noemie , Dumas Elise , Daoud Eric , Grandal Beatriz , Pierga Jean-Yves , Coussy Florence , Kirova Youlia , Alam Elsy el , Bataillon Guillaume , Lae Marick , Llouquet Florence , Reyal Fabien , Hamy Anne-Sophie
Published: December 2020

Introduction

The three different breast cancer subtypes (Luminal,HER2-positive and triple negative (TNBCs) display different natural history and sensitivity to treatment, but little is known about whether residual axillary disease after neoadjuvant chemotherapy (NAC) carries a different prognostic value by BC subtype.

Methods

We retrospectively evaluated axillary involvement (0, 1 to 3 positive nodes, ≥ 4 positive nodes) on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between nodal involvement (ypN) binned into 3 classes (0; [1-3];4 or more), relapse-free survival (RFS) and overall survival (OS) among the global population, and according to BC subtypes.

Results

1197 patients were included in the analysis (luminal (n = 526, 43.9%), TNBCs (n = 376, 31.4%),HER2-positive BCs (n = 295, 24.6%)). After a median follow-up of 110.5 months, ypN was significantly associated with RFS, but this effect was different by BC subtype (Pinteraction= 0.004), and this effect was nonlinear. In the luminal subgroup, RFS was impaired in patients with 4 or more nodes involved (HR=2.8; 95% CI [1.93;4.06],p<0.001) when compared with ypN0, while it was not in patients with 1 to 3 nodes (HR=1.24, 95% CI = [0,86;1.79]). In patients with TNBC, both 1-3N+ and ≥ 4 N+ classes were associated with a decreased RFS (HR=3.19, 95%CI= [2.05; 4.98] and HR=4.83, 95%CI= [3.06; 7.63], respectivelyversusypN0,p< 0.001). Similar decreased prognosis were observed among patients withHER2-positive BC (1-3N+: HR=2.7, 95%CI= [1.64; 4.43] and ≥ 4 N+: HR=2.69, 95%CI= [1.24; 5.8] respectively,p=0.003).

Conclusion

The prognostic value of residual axillary disease should be considered differently in the 3 BC subtypes to accurately stratify patients with a high risk of recurrence after NAC who should be offered second line therapies.
Antibacterial consumption in the context of COVID-19 in Pakistan: an analysis of national pharmaceutical sales data for 2019-20
Authors: Orubu Ebiowei Samuel F. , Malik Farrukh , Figueras Albert , Ching Carly , Fuzail Ahsan M , Wirtz Veronika J. , Zaman Muhammad H.
Published: December 2020

Objectives

Uncertainties in the pharmaceutical management of COVID-19 have led to reports of increased indiscriminate uses of antibiotics. The aim of this study was to investigate this at a national level in Pakistan.

Methods

We used IQVIA pharmaceutical sales volume data to analyze antibiotic consumption for January-April 2020 in Pakistan. The consumption of 77 antibiotics for systemic use in 2020 was calculated, and compared against the same period in 2019 to track changes in total consumption and consumption pattern by six assigned therapeutic groups: tetracyclines, quinolones, beta-lactam penicillins, other-beta-lactams, macrolides and “others” – comprising the remaining groups.

Results

The total consumption for January-April 2020 was 17.76 Defined Daily Doses per 1000 population per day (a 18.8% decrease from 2019). Quinolones, beta-lactam penicillins, other-beta-lactams, and macrolides constituted 80% of total consumption. There were increases between February-April 2020 of macrolides and “others”. In March 2020, 112768 more people consumed a macrolide per day compared to March 2019; mostly azithromycin.

Conclusions

Total consumption decreased in the first four months of 2020 compared to 2019, possibly arising from a combination of several pre-existing and concurrent economic conditions as well as the lockdown situation. However, the results suggest an increase in the consumption of the macrolide class of antibiotics during the early phase of COVID-19 in Pakistan.
What is the probability that this patient, who presents to a UK hospital, will be diagnosed with Covid-19? Prospective validation of the open-source CovidCalculatorUK resource
Authors: Chapman George , Mundell Lewis , Harrison Charlotte H. , Cargill Tamsin , Keating Odhran , Johnson Mark , Smith Andrew
Published: December 2020

Introduction

The novel coronavirus SARS-CoV2 and the associated disease, Covid-19, continue to pose a global health threat. The CovidCalculatorUK is an open-source online tool (covidcalculatoruk.org) that estimates the probability that an individual patient, who presents to a UK hospital, will later test positive for SARS-CoV2. The objective is to aid cohorting decisions and minimise nosocomial transmission of SARS-CoV2.

Methods

This n = 500 prospective, observational, multicentre, validation study compared the CovidCalculatorUK’s estimated probability of Covid-19 with the first SARS-CoV2 oropharyngeal/nasopharyngeal swab result for individual patients admitted to hospital during the study period (01.04.20 − 18.05.20). A comparison with senior clinicians’ estimates of the probability of Covid-19 was also made.

Results

Patients who were prospectively grouped, by the CovidCalculatorUK, into 0-30% estimated probability, 30-60% and 60-100% estimated probability went on to have first swab SARS-CoV2 positive results in: 15.7%, 30.5% and 61.9% of cases, respectively. CovidCalculatorUK performance demonstrated an area under the curve of 0.76 (95% CI 0.71 – 0.81) (p < 0.001). Senior clinician stratification of the estimated probability of Covid-19 performed similarly to the CovidCalculatorUK.

Conclusion

The CovidCalculatorUK provides a reasonably accurate estimate of the probability of an individual testing positive on their first SARS-CoV2 nasopharyngeal/oropharyngeal swab. The CovidCalculatorUK output performs similarly to a senior clinician’s estimate. Further evolution of the calculator may improve performance.