bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure–Response Relationship of Tranexamic Acid in Cardiac Surgery
Authors: Zufferey Paul Jacques , Lanoiselée Julien , Graouch Billal , Vieille Baptiste , Delavenne Xavier , Ollier Edouard 
Published: December 2020

Background
It is unclear whether high-dose regimens of tranexamic acid in cardiac surgery (total dose, 80 to 100 mg/kg) confer a clinical advantage over low-dose regimens (total dose, approximately 20 mg/kg), particularly as tranexamic acid–associated seizure may be dose-related. The authors’ aim was to characterize the exposure–response relationship of this drug.

Methods
Databases were searched for randomized controlled trials of intravenous tranexamic acid in adult patients undergoing cardiopulmonary bypass surgery. Observational studies were added for seizure assessment. Tranexamic acid concentrations were predicted in each arm of each study using a population pharmacokinetic model. The exposure–response relationship was evaluated by performing a model-based meta-analysis using nonlinear mixed-effect models.

Results
Sixty-four randomized controlled trials and 18 observational studies (49,817 patients) were included. Seventy-three different regimens of tranexamic acid were identified, with the total dose administered ranging from 5.5 mg/kg to 20 g. The maximum effect of tranexamic acid for postoperative blood loss reduction was 40% (95% credible interval, 34 to 47%), and the EC50 was 5.6 mg/l (95% credible interval, 0.7 to 11 mg/l). Exposure values with low-dose regimens approached the 80% effective concentration, whereas with high-dose regimens, they exceeded the 90% effective concentration. The predicted cumulative blood loss up to 48 h postsurgery differed by 58 ml between the two regimens, and the absolute difference in erythrocyte transfusion rate was 2%. Compared to no tranexamic acid, low-dose and high-dose regimens increased the risk of seizure by 1.2-fold and 2-fold, respectively. However, the absolute risk increase was only clinically meaningful in the context of prolonged open-chamber surgery.

Conclusions
In cardiopulmonary bypass surgery, low-dose tranexamic acid seems to be an appropriate regimen for reducing bleeding outcomes. This meta-analysis has to be interpreted with caution because the results are observational and dependent on the lack of bias of the predicted tranexamic acid exposures and the quality of the included studies.

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Availability of Donor Human Milk Decreases the Incidence of Necrotizing Enterocolitis in VLBW Infants
Authors: Cohen Morris , Steffen Eileen , Axelrod Randi , Patel Shalini N. , Toczylowski Krystyna , Perdon Christine , Brown David , Kaliappan Sankar , Myers Michael 
Published: December 2020

Background:
Human milk feeding is associated with decreased risk of necrotizing enterocolitis (NEC).

Purpose:
To determine whether a quality improvement project in New Jersey neonatal intensive care units (NICUs) to promote human milk (HM) feedings would be associated with a decrease in NEC.

Methods:
Fourteen New Jersey NICUs engaged in efforts to reduce infection and promote HM feeding in very low birth-weight (VLBW) infants. Donor human milk (DHM) availability and NEC rates were assessed.

Results:
From 2009 to 2016, NICUs with DHM increased from 0 to 7. VLBW infants discharged on any HM increased from 35% in 2007 before the formation of the New Jersey NICU Collaborative to more than 55% in 2016. Time to first oropharyngeal colostrum decreased from 37 to 30 hours from 2014 to 2016. HM at first feeding increased from 71% in 2013 to 82% in 2016. There was an increase in the percentage of feeds that were HM over the first 7 days of feeding. Analyses of data from 9400 VLBW infants born between 2009 and 2016 showed that the incidence of NEC when DHM was not available was 5.1% (367/7182) whereas the incidence when DHM was available (64/2218) was significantly lower (2.9%; P < .0001).

Implications for Practice:
These findings show advantages of feeding HM and effectiveness of forming an NICU collaborative for improving care for preterm infants.

Implications for Research:
New research projects should measure the quantity of HM consumed daily during the entire NICU stay and assess the timing and amount of HM consumption in relationship to incidence of NEC and infection in neonates.
A ROD–CONE DYSTROPHY IS SYSTEMATICALLY ASSOCIATED TO THE RTN4IP1 RECESSIVE OPTIC ATROPHY
Authors: Meunier Isabelle , Bocquet Béatrice , Charif Majida , Dhaenens Claire-Marie , Manes Gael , Amati-Bonneau Patrizia , Roubertie Agathe , Zanlonghi Xavier , Lenaers Guy 
Published: December 2020

Purpose:

RTN4IP1 biallelic mutations cause a recessive optic atrophy, sometimes associated to more severe neurological syndromes, but so far, no retinal phenotype has been reported in RTN4IP1 patients, justifying their reappraisal.

Methods:
Seven patients from four families carrying biallelic RTN4IP1 variants were retrospectively reviewed, with emphasis on their age of onset, visual acuity, multimodal imaging including color and autofluorescence frames, spectral-domain optical coherence tomography with RNFL and macular analyses.

Results:
Seven patients from four RTN4IP1 families developed in their first decade of life a bilateral recessive optic atrophy with severe central visual loss, and primary nystagmus developed in 5 of 7 patients. Six patients were legally blind. In a second stage, the seven individuals developed a rod–cone dystrophy, sparing the macular zone and the far periphery. This retinal damage was identified by 55° field fundus autofluorescence frames and also by spectral-domain optical coherence tomography scans of the temporal part of the macular zone in five of the seven patients. Full-field electroretinography measurements disclosed reduced b-wave amplitude of the rod responses in all patients but two. Family 4 with the p.R103H and c.601A > T (p.K201*) truncating mutation had further combined neurological signs with cerebellar ataxia, seizures, and intellectual disability.

Conclusion:

RTN4IP1 recessive optic atrophy is systematically associated to a rod–cone dystrophy, which suggests that both the retinal ganglion cells and the rods are affected as a result of a deficit in the mitochondrial respiratory chain. Thus, systematic widefield autofluorescence frames and temporal macular scans are recommended for the evaluation of patients with optic neuropathies.
LONG-TERM INCIDENCE AND RISK FACTORS OF OCULAR HYPERTENSION FOLLOWING DEXAMETHASONE-IMPLANT INJECTIONS
Authors: Rezkallah Amina , Mathis Thibaud , Abukhashabah Amro , Voirin Nicolas , Malclès Ariane , Agard Émilie , Lereuil Théo , Denis Philippe , Dot Corinne , Kodjikian Laurent 
Published: December 2020

Purpose:To analyze the incidence, risk factors, and time to onset of ocular hypertension (OHT) after intravitreal injections (IVI) of dexamethasone implant and to evaluate the long-term cumulative probability of intraocular pressure elevation.Methods:Eyes of patients having received at least one dexamethasone implant IVI between October 2010 and February 2015 were included in the present study. Ocular hypertension was defined as intraocular pressure > 25 mmHg and/or an increase of 10 mmHg over the follow-up period compared with baseline intraocular pressure.Results:Four hundred ninety-four eyes were studied in 410 patients. For a total of 1,371 IVI, the incidence of OHT was 32.6% in the study eyes with a mean follow-up period of 30 months (3–62.5) and a median follow-up of 29 months. Pressure-lowering treatment was introduced for 36.9% of eyes. Topical treatment alone was sufficient to manage OHT in 97%. Young age, male sex, uveitis and retinal vein occlusion, and glaucoma treated with a double- or triple-combination topical pressure-lowering medication were found to be risk factors for OHT. The incidence of OHT did not change with an increase in the number of IVI, and there was no cumulative effect, defining by an increase of the incidence of OHT in patients after repeated IVI (P= 0.248).Conclusion:This study confirmed that OHT is of moderate incidence, transient, controlled by topical treatment and provides data on the long-term cumulative probability of intraocular pressure elevation in a large cohort of eyes treated with dexamethasone implant IVI. Repeat injections of dexamethasone implant neither increase nor decrease the risk of OHT.
History, presence, and future of mitomycin C in glaucoma filtration surgery
Authors: Wolters Jarno E.J. , van Mechelen Ralph J.S. , Al Majidi Rana , Pinchuk Leonard , Webers Carroll A.B. , Beckers Henny J.M. , Gorgels Theo G.M.F. 
Published: December 2020

Purpose of review
Mitomycin C (MMC) is an alkylating agent with extraordinary ability to crosslink DNA, preventing DNA synthesis. By this virtue, MMC is an important antitumor drug. In addition, MMC has become the gold standard medication for glaucoma filtration surgery (GFS). This eye surgery creates a passage for drainage of aqueous humor (AqH) out of the eye into the sub-Tenon's space with the aim of lowering the intraocular pressure. A major cause of failure of this operation is fibrosis and scarring in the sub-Tenon's space, which will restrict AqH outflow. Intraoperative application of MMC during GFS has increased GFS success rate, presumably mainly by reducing fibrosis after GFS. However, still 10% of glaucoma surgeries fail within the first year.

Recent findings
In this review, we evaluate risks and benefits of MMC as an adjuvant for GFS. In addition, we discuss possible improvements of its use by adjusting dose and method of administration.

Summary
One way of improving GFS outcome is to prolong MMC delivery by using a drug delivery system.
Visual outcomes after cataract surgery: topical nonsteroidal anti-inflammatory drug prophylaxis compared with prednisolone
Authors: Shorstein Neal H. , Carolan James , Liu Liyan , Alexeeff Stacey E. , Amsden Laura B. , Herrinton Lisa J. 
Published: December 2020

Purpose:
To compare visual outcomes in patients without a history of macular edema after phacoemulsification using combination topical nonsteroidal anti-inflammatory drug plus prednisolone with prednisolone alone.

Setting:
Kaiser Permanente Northern California, USA.

Design:
Retrospective cohort study.

Methods:
Information was obtained from the electronic health record. The first measure of corrected distance visual acuity (CDVA) recorded during the period 3 weeks to 1 year after phacoemulsification was obtained. Confounding factors and clustering of eyes within patients were adjusted using linear mixed effects regression models for the continuous outcome of CDVA improvement and general estimating equations for the dichotomous outcome of 20/20 or better vs 20/25 or worse.

Results:
The study included 62 700 health plan members of whom 26,309 (42%) used topical prednisolone alone, whereas 36,391 (58%) used combination treatment. The mean within-person change in CDVA from the preoperative measurement to the postoperative measurement was the same (−0.43 logMAR) for patients in the 2 groups. However, the group that received combination treatment was somewhat more likely to achieve CDVA of 20/20 or better (odds ratio 1.24 with 95% CI, 1.20-1.28).

Conclusions:
In this large study of cataract surgery patients, a small statistically significant association of combination treatment compared with prednisolone alone was observed.
Reoperation for complications within 90 days of minimally invasive glaucoma surgery
Authors: Shalaby Wesam Shamseldin , Bechay Joseph , Myers Jonathan S. , Lee Daniel , Razeghinejad Reza , Kolomeyer Natasha Nayak , Katz L. Jay , Shukla Aakriti Garg 
Published: December 2020

Objective:
To describe reoperations that occurred within 90 days of minimally invasive glaucoma surgery (MIGS) at a single institution over a 30-month period.

Setting:
Tertiary care hospital.

Design:
Retrospective case series.

Methods:
Charts of adult patients who underwent trabecular microbypass stents, gel microstents, and goniotomy procedures (including gonioscopy-assisted transluminal trabeculotomy) from October 1, 2017, to March 15, 2020, at Wills Eye Hospital were examined. Outcome measures were unanticipated reoperations within the first 90 days after MIGS procedures and the complications that led to these reoperations.

Results:
A total of 448 MIGS procedures were performed on 436 eyes of 348 patients over a 30-month period by 6 glaucoma surgeons. Of these, 206 (46.0%) were trabecular microbypass stents (198 iStent/iStent inject and 8 Hydrus), 152 (33.9%) were gel microstents, and 90 (20.1%) were goniotomy procedures. Combined phacoemulsification took place in 256 eyes (58.7%). Reoperation within 90 days took place in 23 (5.3%) of 436 eyes, including 16 (10.5%) of 152 eyes in the gel microstent group, 4 (2.0%) of 198 eyes in iStent/iStent inject group, and 3 (3.3%) of 90 eyes in the goniotomy group. Indications for reoperation were elevated intraocular pressure (IOP) in 16 (69.6%) of 23 eyes, gel microstent tip exposure with wound leakage in 3 (13.0%) of 23 eyes, and early gel microstent encapsulation without elevated IOP in 1 (4.3%) of 23 eyes. Two (8.7%) of 23 eyes required reoperation for intraocular lens complications, whereas 1 (4.3%) of 23 eyes had elevated IOP and aphakia requiring reoperation.

Conclusions:
The rate of reoperation within the first 90 days after MIGS was low. Elevated IOP and complications associated with gel microstents were the main indications for reoperation.
Optical function of intraocular lenses in different opacification patterns: metrology analysis of 67 explants
Authors: Łabuz Grzegorz , Yildirim Timur M. , Khoramnia Ramin , Son Hyeck-Soo , Auffarth Gerd U. 
Published: December 2020

Purpose:
To determine how the type of opacification would have compromised the function of intraocular lenses (IOLs) prior to explantation using metrology.

Setting:
David J Apple Laboratory, Heidelberg, Germany.

Design:
Laboratory investigation.

Methods:
Of 67 explanted IOLs, 28 with homogeneous calcification, 21 with localized calcification, and 18 subluxated IOLs without calcification that served as controls were identified. The modulation transfer function (MTF) cutoff (0.43 at 100 lp/mm) was used to define decreased optical quality, following the manufacturers' guidelines for IOL testing. Light scattering was evaluated in vitro using a clinical device.

Results:
Only 1 control IOL demonstrated a decreased MTF compared with 4 and 15 in the homogeneous and localized groups, respectively. The MTF-derived metrics did not differ between the homogeneous and control IOLs (P = .99), but both showed better performance than those with localized opacification (P < .001). The median straylight parameter in the homogeneous pattern was 181.8 deg2/sr (108.5 to 244.1 deg2/sr), but in the localized group, it was less [69.8 (17.7 to 250.8) deg2/sr] (P = .02). Both opacification patterns yielded a significant straylight increase compared with the controls (P < .001).

Conclusions:
The study demonstrated that optical quality differed between the 2 types of opacification. The centrally localized pattern showed a significant MTF reduction, indicating a larger potential to affect patient visual acuity. Although localized calcification demonstrated lower straylight than that found in the homogeneous form, both conditions may cause severe glare phenomena.
Nosocomial pneumonia diagnosis revisited
Authors: Koulenti Despoina , Zhang Yuchi , Fragkou Paraskevi C. 
Published: December 2020

Purpose of review
Nosocomial pneumonia represents a significant burden even for the most resilient healthcare systems. Timely and reliable diagnosis is critical but remains a deficient field. This review critically revises the latest literature on the diagnosis of nosocomial pneumonia, including advances in imaging techniques, as well as the utility of rapid microbiological tests in establishing the etiological diagnosis.

Recent findings
Studies on low radiation computed tomography (CT) and lung ultrasound (LUS) have shown promising results for early nosocomial pneumonia diagnosis; however, further data on their sensitivity and specificity are needed, especially for picking up subtle and nonspecific radiographic findings. Moreover, data supporting their superiority in pneumonia diagnosis is still limited. As for microbiological diagnosis, several culture-independent molecular diagnostic techniques have been developed, identifying both causative microorganisms as well as determinants of antimicrobial resistance, but more studies are needed to delineate their role in nosocomial pneumonia diagnosis.

Summary
The development of nonculture dependent tests has launched a new era in microbiological nosocomial pneumonia diagnosis. These modalities along with the use of LUS and/or low radiation CT might improve the sensitivity and specificity of nosocomial pneumonia diagnosis, enhance early detection and guide the antimicrobial therapy but more studies are needed to further evaluate them and determine their role for the routine clinical practice.
Emerging cellular and pharmacologic therapies for acute respiratory distress syndrome
Authors: Gonzalez Hector , Horie Shahd , Laffey John G. 
Published: December 2020

Purpose of review
Advances in our understanding of the pathophysiology and biology of ARDS has identified a number of promising cellular and pharmacological therapies. These emerging therapeutics can modulate the immune response, reduce epithelial injury, target endothelial and vascular dysfunction, have anticoagulant effects, and enhance ARDS resolution.

Recent findings
Mesenchymal stromal cell therapy shows promise in earlier phase clinical testing, whereas a number of issues regarding clinical translation, such as donor and effect variability, are currently being optimized to enable larger scale clinical trials. Furthermore, a number of promising mesenchymal stromal cell therapy clinical studies for COVID-19-induced ARDS are underway. Recent studies provide support for several emerging ARDS pharmacotherapies, including steroids, statins, vitamins, anticoagulants, interferons, and carbon monoxide. The history of unsuccessful clinical trials of potential therapies highlights the challenges to successful translation for this heterogeneous clinical syndrome. Given this, attention has focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies, i.e. ‘precision medicines’.

Summary
Mesenchymal stromal cells, steroids, statins, vitamins, anticoagulants, interferons and carbon monoxide have therapeutic promise for ARDS. Identifying ARDS sub-populations most likely to benefit from targeted therapies may facilitate future advances.
Ventilation of coronavirus disease 2019 patients
Authors: Grasselli Giacomo , Cattaneo Emanuele , Scaravilli Vittorio 
Published: December 2020

Purpose of review
To summarize the current knowledge of pathophysiology and ventilatory management of acute respiratory failure in COVID-19.

Recent findings
Early reports suggested that COVID-19 is an ‘atypical ARDS’ with profound hypoxemia with normal respiratory system compliance (Crs). Contrarily, several more populated analyses showed that COVID-19 ARDS has pathophysiological features similar to non-COVID-19 ARDS, with reduced Crs, and high heterogeneity of respiratory mechanics, hypoxemia severity, and lung recruitability. There is no evidence supporting COVID-19-specific ventilatory settings, and the vast amount of available literature suggests that evidence-based, lung-protective ventilation (i.e. tidal volume ≤6 ml/kg, plateau pressure ≤30 cmH2O) should be enforced in all mechanically ventilated patients with COVID-19 ARDS. Mild and moderate COVID-19 can be managed outside of ICUs by noninvasive ventilation in dedicated respiratory units, and no evidence support an early vs. late intubation strategy. Despite widely employed, there is no evidence supporting the efficacy of rescue therapies, such as pronation, inhaled vasodilators, or extracorporeal membrane oxygenation.

Summary
Given the lack of evidence-based specific ventilatory strategies and a large amount of literature showing pathophysiological features similar to non-COVID-19 ARDS, evidence-based lung-protective ventilatory strategies should be pursued in all patients with COVID-19 ARDS.
Advances in newer basal and bolus insulins: impact on type 1 diabetes
Authors: Vliebergh Joke , Lefever Eveline , Mathieu Chantal 
Published: December 2020

Purpose of review
Insulin administration is vitally important to maintain a good glycaemic control in people with type 1 diabetes mellitus (T1DM). The purpose of this review is to give a clinically relevant overview of the newer basal and bolus insulin analogues and to highlight their practicalities of use and advantages in specific categories of patients with T1DM.

Recent findings
Second-generation rapid-acting insulin analogues (i.e. faster insulin aspart and ultrarapid-acting lispro) have shown to be safe, efficient and superior in controlling postprandial plasma glucose levels without an increase in hypoglycaemia. The newest basal insulin analogues, insulin glargine U300 and degludec, have proven to be efficient in reducing hypoglycaemic events due to a more stable action profile.

Summary
The second-generation rapid-acting and basal insulin analogues approach better the desired physiological insulin pattern of the beta cell. Due to a faster absorption, it is possible to inject the prandial insulin analogues more closely or even after meals without compromising postprandial glucose control. Due to more stable release patterns, basal insulins now have more reliable and longer profiles, covering basal insulin demands in a superior way, leading to a better glycaemic control with less hypoglycaemia (especially nocturnal events) and an improved quality of life.
Dysfunctional voiding: update on evaluation and treatment
Authors: Bauer Abbie 
Published: December 2020

Purpose of review
This review will be covering dysfunctional voiding, its diagnosis, and treatment options. This will focus primarily on dysfunctional voiding rather than all lower urinary tract dysfunction and we will focus on some of the newer findings and progress within this disease.

Recent findings
Dysfunctional voiding is the inappropriate sphincter and pelvic floor constriction during voiding in an otherwise neurologically normal child. This has a wide spectrum of symptoms and can lead to a number of complications such as chronic kidney disease and poor quality of life if not appropriately addressed. Dysfunctional voiding is diagnosed with a careful examination and history with further imaging including a renal ultrasound and uroflowmetry to confirm the diagnosis. Urotherapy and biofeedback are the first and second-line treatments respectively and lead to significant improvement or cure in the majority of patients. For refractory patients, additional therapy options include use of α-blockers, botulinum injection, and electroneurostimulation, though the majority of the literature surrounding the use of these therapies consists of small studies with heterogenous causes of voiding dysfunction.

Summary
Dysfunctional voiding is a common urologic complaint that has many excellent options for improving the patient's voiding issues and should be considered in patients with voiding dysfunction.