bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a Clearer Causal Question Underlying the Association Between Cancer and Dementia
Authors: Rojas-Saunero L. Paloma , van der Willik Kimberly D. , Schagen Sanne B. , Ikram M. Arfan , Swanson Sonja A. 
Published: March 2024

Background:
Several observational studies have described an inverse association between cancer diagnosis and subsequent dementia risk. Multiple biologic mechanisms and potential biases have been proposed in attempts to explain this association. One proposed explanation is the opposite expression of Pin1 in cancer and dementia, and we use this explanation and potential drug target to illustrate the required assumptions and potential sources of bias for inferring an effect of Pin1 on dementia risk from analyses measuring cancer diagnosis as a proxy for Pin1 expression.

Methods:
We used data from the Rotterdam Study, a population-based cohort. We estimate the association between cancer diagnosis (as a proxy for Pin1) and subsequent dementia diagnosis using two different proxy methods and with confounding and censoring for death addressed with inverse probability weights. We estimate and compare the complements of a weighted Kaplan–Meier survival estimator at 20 years of follow-up.

Results:
Out of 3634 participants, 899 (25%) were diagnosed with cancer, of whom 53 (6%) had dementia, and 567 (63%) died. Among those without cancer, 15% (411) were diagnosed with dementia, and 667 (24%) died over follow-up. Depending on the confounding and selection bias control, and the way in which cancer was used as a time-varying proxy exposure, the risk ratio for dementia diagnosis ranged from 0.71 (95% confidence interval [CI] = 0.49, 0.95) to 1.1 (95% CI = 0.79, 1.3).

Conclusion:
Being explicit about the underlying mechanism of interest is key to maximizing what we can learn from this cancer-dementia association given available or readily collected data, and to defining, detecting, and preventing potential biases.
Recurrent alcohol-associated hepatitis is common and is associated with increased mortality
Authors: Gratacós-Ginès Jordi , Ruz-Zafra Pilar , Celada-Sendino Miriam , Martí-Carretero Aina , Pujol Clàudia , Martín-Mateos Rosa , Echavarría Víctor , Frisancho Luis E. , García Sonia , Barreales Mónica , Tejedor-Tejada Javier , Vázquez-Rodríguez Sergio , Cañete Nuria , Fernández-Carrillo Carlos , Valenzuela María , Martí-Aguado David , Horta Diana , Quiñones Marta , Bernal-Monterde Vanesa , Acosta Silvia , Artaza Tomás , Pinazo José , Villar-Lucas Carmen , Clemente-Sánchez Ana , Badia-Aranda Ester , Giráldez-Gallego Álvaro , Rodríguez Manuel , Sancho-Bru Pau , Cabezas Joaquín , Ventura-Cots Meritxell , Fernández-Rodríguez Conrado , Aguilera Victoria , Tomé Santiago , Bataller Ramon , Caballería Juan , Pose Elisa ,   REHALC Registry investigators
Published: March 2024

Background and Aims:
Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described.

Approach and Results:
A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7–36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8–29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p<0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11–2.18]).

Conclusions:
RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH.
Surgical drainage methods during pars plana vitrectomy for rhegmatogenous retinal detachment: a systematic review and meta-analysis
Authors: Grad Justin R. , Hatamnejad Amin , Huan Peter W. , Popovic Marko M. , McKay Bryon R. , Kertes Peter J. , Muni Rajeev H. 
Published: March 2024

Purpose:
To assess efficacy and safety outcomes of subretinal fluid drainage methods during pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD).

Methods:
A systematic search strategy was conducted of studies published between January 2000 and October 2022. Included studies reported on either the safety or efficacy of two or more drainage methods during PPV for RRD patients.

Results:
Two randomized and five observational studies consisting of 1524 eyes were included. Best corrected visual acuity at last study observation and primary reattachment rate were similar across groups. A significantly lower risk of epiretinal membrane formation (ERM) was associated with draining subretinal fluid through pre-existing retinal breaks (PRB) (RR= 0.70, 95% CI=[0.60, 0.83], p=<0.01, I2=0%) or with perfluorocarbon liquid (PFCL) (RR=0.70, 95% CI=[0.59, 0.83], p=<0.01, I2=0%) compared to posterior retinotomy (PR). The risk of an abnormal foveal contour was significantly greater in PFCL-treated eyes relative to PR (RR=1.56, 95% CI=[1.13, 2.17], p=<0.01, I2=0%).

Conclusions:
No significant differences were observed in final BCVA at last study observation and primary reattachment rates across different drainage methods. There remains limited information on the topic and future research is warranted.
Visual Outcomes after Internal Limiting Membrane Peeling vs. Flap in the Closure of Full Thickness Macular Holes
Authors: Suarez Mallory K. , Wang Sean K. , Hayes Bartlett , Greven Margaret A. , Shah Rajiv E. , Greven Craig , Russell Greg , Ong Sally S. 
Published: March 2024

Purpose:To examine postoperative outcomes of internal limiting membrane peeling (ILMP) versus flap (ILMF) in the closure of full thickness macular holes (FTMH).Methods:Retrospective chart review of patients who underwent pars plana vitrectomy and gas tamponade with ILMP or ILMF to close FTMH at the Atrium Health Wake Forest Baptist from January 2012 to October 2022 with at least 3 months follow up. Main outcome measures were type 1 primary FTMH closure and postoperative best corrected visual acuity (BCVA) in mean logMAR.Results:130 and 30 eyes underwent ILMP and ILMF respectively. There were no significant differences in baseline characteristics between the groups. 96% of ILMP eyes and 90% of ILMF eyes achieved primary hole closure (p=0.29). Among all eyes with primary hole closure, BCVA at 1 year was not different between the groups but when stratified by lens status, was superior in the ILMP versus ILMF group in pseudophakic eyes: the estimated least-squares mean BCVA (Snellen equivalent) [95% confidence interval] was 0.42 (20/50) [0.34, 0.49] in the ILMP group and 0.71 (20/100) [0.50, 0.92] in the ILMF group.Conclusions:ILMP and ILMF techniques yielded similarly high FTMH closure rates. In pseudophakic eyes with primary hole closure, ILMF eyes had worse BCVA at 1 year.
Rahnella Aquatilis Endophthalmitis after Intravitreal Injection in an Immunocompetent Patient
Authors: Williams Parker J. , Xue Gilbert , Ross Bing X. , White Erika , Shammas Lisa , Yoganathan Pradeepa , Chapman Christopher , Lin Xihui 
Published: March 2024

Purpose:
To present a novel case of exogenous Rahnella aquatilis endophthalmitis following an intravitreal injection.

Methods:
Case report

Results:
A 74-year-old male presented with acute progressive vision loss and pain in the left eye, 5 days after an intravitreal injection for diabetic macular edema. The patient was diagnosed with exogenous endophthalmitis and empirically treated with intravitreal injections of vancomycin and ceftazidime as well as topical and oral ciprofloxacin. In follow up two days later, the patient was treated with preoperative povidone-iodine followed by prompt vitrectomy with additional vancomycin and ceftazidime due to pharmacy sterile hood issues that delayed antibiotic availability. Microbiological cultures and two mass spectrometry identification tests confirmed the diagnosis of exogenous Rahnella aquatilis endophthalmitis. Despite the presence of scattered retinal hemorrhagic infarcts involving the macula and subsequent full-thickness atrophic macular holes seen in follow up, the patient achieved a favorable anatomical and functional outcome of BCVA 20/80 at 1 year of follow-up.

Conclusion:
This case highlights the occurrence of exogenous Rahnella aquatilis endophthalmitis following an intravitreal injection for diabetic macular edema. Prompt diagnosis and treatment produced a favorable outcome relative to other typical Gram-negative Enterobacteriaceae organisms.
Scheimpflug-Based Tomographic Risk Factors for the Development of Acute Corneal Hydrops in Keratoconus
Authors: Yu Sarah N. , Gad Rania , Kutler Rachel , Trief Danielle 
Published: March 2024

Purpose:
The purpose of this study was to assess the risk factors that predispose patients with keratoconus to develop acute corneal hydrops (ACH), including both clinical and tomographic risk factors. We additionally describe tomographic changes of the cornea over time after ACH.

Methods:
We retrospectively reviewed patients with keratoconus who were followed at our institution from January 2015 to May 2023. Control eyes, defined as eyes with advanced keratoconus (stage IV Amsler–Krumeich classification on initial examination) were compared with eyes that developed ACH. Demographic, clinical, and tomographic factors were investigated. Visual acuity, keratometry, and corneal thickness were assessed at each follow-up visit to monitor progression over time.

Results:
Twenty-three eyes of 19 patients developed ACH over the follow-up period. The incidence of known clinical associations including seasonal allergies, eye rubbing, snoring, asthma, and eczema was similar between the hydrops and control groups. There was a higher incidence of Down syndrome in the hydrops group (P = 0.04). Eyes that developed hydrops had similar best corrected visual acuity on initial examination, but had steeper keratometry (P = 0.003) and thinner corneas (P < 0.001) than controls at baseline. After hydrops, progressive corneal flattening and reduced maximum keratometry occurred over time. However, final best corrected visual acuity was worse compared with initial examination before hydrops (P = 0.03), as well as compared with control eyes (P < 0.001).

Conclusions:
Risk factors of developing ACH include steep keratometry and thin corneas as well as Down syndrome. Although corneal flattening will occur after resolution of acute corneal edema, visual acuity worsened after ACH.
Gene therapy for age-related macular degeneration: potential, feasibility, and pitfalls
Authors: Berkowitz Sean T. , Finn Avni P. 
Published: March 2024

Purpose of review
The landscape for age-related macular degeneration (AMD) is rapidly changing with addition of biosimilars and now United States Food and Drug Administration (FDA) approved nonneovascular AMD (nnAMD) treatment options. These developments have inspired a burgeoning pipeline of gene therapy approaches focused on similar antivascular endothelial growth factors (VEGF) and complement related pathways. Historic and more recent setbacks in the gene therapy pipeline, including intraocular inflammatory reactions, have raised important concerns for adverse events related to AMD therapeutics both for gene and nongene approaches. The specific clinical profile of these therapeutics approaching later stage clinical trials are complex and under active investigation; however, these options hold promise to disrupt the current landscape and change management paradigms for one of the leading causes of vision loss worldwide.

Recent findings
This review covers current gene therapy approaches for neovascular AMD (nAMD) and nnAMD. Intravitreal, suprachoroidal, and subretinal delivery routes are discussed with attention to technical procedure, capabilities for transgene delivery to target tissue, immunogenicity, and collateral effects. Suprachoroidal delivery is an emerging approach which may bridge some of the practical drawbacks for intravitreal and subretinal methods, though with less elaborated immunologic profile. In parallel to delivery modification, viral vectors have been cultivated to target specific cells, with promising enhancements in adeno-associated viral (AAV) vectors and persistent interest in alternate viral and nonviral delivery vectors. Ongoing questions such as steroid or immunosuppressive regimen and economic considerations from a payer and societal perspective are discussed.

Summary
The present review discusses emerging gene therapy options which could foster new, more durable nAMD and nnAMD therapeutics. These options will need refinement with regards to route, vector, and dosage, and specialists must decipher the specific clinical risk benefit profile for individual patients. Ongoing concerns for immunogenicity or dosage related adverse events could stifle progress, while further vector development and refined delivery techniques have the potential to change the safety and efficacy of currently options in the pipeline.
Characterizing high-cost healthcare users among adults with back pain in Ontario, Canada: a population-based cohort study
Authors: Wong Jessica J. , Côté Pierre , Tricco Andrea C. , Watson Tristan , Rosella Laura C. 
Published: March 2024

Abstract
Some patients with back pain contribute disproportionately to high healthcare costs; however, characteristics of high-cost users with back pain are not well defined. We described high-cost healthcare users based on total costs among a population-based cohort of adults with back pain within the Ontario government's single-payer health system across sociodemographic, health, and behavioural characteristics. We conducted a population-based cohort study of Ontario adult (aged 18 years or older) respondents of the Canadian Community Health Survey (CCHS) with back pain (2003-2012), linked to administrative data (n = 36,605; weighted n = 2,076,937, representative of Ontario). Respondents were ranked based on gradients of total healthcare costs (top 1%, top 2%-5%, top 6%-50%, and bottom 50%) for 1 year following the CCHS survey, with high-cost users as top 5%. We used multinomial logistic regression to investigate characteristics associated with the 4 cost groups. Top 5% of cost users accounted for 49% ($4 billion CAD) of total healthcare spending, with inpatient hospital care as the largest contributing service type (approximately 40% of costs). Top 5% high-cost users were more likely aged 65 years or older (ORtop1% = 16.6; ORtop2-5% = 44.2), with lower income (ORtop1% = 3.6; ORtop 2-5% = 1.8), chronic disease(s) (ORtop1% = 3.8; ORtop2-5% = 1.6), Aggregated Diagnosis Groups measuring comorbidities (ORtop1% = 25.4; ORtop2-5% = 13.9), and fair/poor self-rated general health (ORtop1% = 6.7; ORtop2-5% = 4.6) compared with bottom 50% users. High-cost users tended to be current/former smokers, obese, and report fair/poor mental health. High-cost users (based on total costs) among adults with back pain account for nearly half of all healthcare spending over a 1-year period and are associated with older age, lower income, comorbidities, and fair/poor general health. Findings identify characteristics associated with a high-risk group for back pain to inform healthcare and public health strategies that target upstream determinants.
Individual Patient Comorbidities and Effect on Cochlear Implant Performance
Authors: Dang Sabina , Kallogjeri Dorina , Dizdar Karmela , Lee David , Bao James W. , Varghese Jordan , Walia Amit , Zhan Kevin , Youssef Stephanie , Durakovic Nedim , Wick Cameron C. , Herzog Jacques A. , Buchman Craig A. , Piccirillo Jay F. , Shew Matthew A. 
Published: March 2024

AbstractObjectiveTo examine the association between preoperative comorbidities and cochlear implant speech outcomes.Study DesignRetrospective cohort.SettingTertiary referral center.PatientsA total of 976 patients who underwent cochlear implantation (CI) between January 2015 and May 2022. Adult patients with follow-up, preoperative audiologic data, and a standardized anesthesia preoperative note were included.ExposureAdult Comorbidity Evaluation 27 (ACE-27) based on standardized anesthesia preoperative notes.Main Outcome MeasuresPostoperative change in consonant–nucleus–consonant (CNC) score, AzBio Sentence score in quiet, and AzBio + 10 dB signal-to-noise ratio (SNR). Sentence score of the implanted ear at 3, 6, and 12 months.ResultsA total of 560 patients met inclusion criteria; 112 patients (20%) had no comorbidity, 204 patients (36.4%) had mild comorbidities, 161 patients (28.8%) had moderate comorbidities, and 83 patients (14.8%) had severe comorbidities. Mixed model analysis revealed all comorbidity groups achieved a clinically meaningful improvement in all speech outcome measures over time. This improvement was significantly different between comorbidity groups over time for AzBio Quiet (p= 0.045) and AzBio + 10 dB SNR (p= 0.0096). Patients with severe comorbidities had worse outcomes. From preop to 12 months, the estimated marginal mean difference values (95% confidence interval) between the no comorbidity group and the severe comorbidity group were 52.3 (45.7–58.9) and 32.5 (24.6–40.5), respectively, for AzBio Quiet; 39.5 (33.8–45.2) and 21.2 (13.6–28.7), respectively, for AzBio + 10 dB SNR; and 43.9 (38.7–49.0) and 31.1 (24.8–37.4), respectively, for CNC.ConclusionsComorbidities as assessed by ACE-27 are associated with CI performance. Patients with more severe comorbidities have clinically meaningful improvement but have worse outcome compared to patients with no comorbidities.
Status epilepticus: what's new for the intensivist
Authors: Benghanem Sarah , Pruvost-Robieux Estelle , Neligan Aidan , Walker Matthew C. 
Published: March 2024

Purpose of review
Status epilepticus (SE) is a common neurologic emergency affecting about 36.1/100 000 person-years that frequently requires intensive care unit (ICU) admission. There have been advances in our understanding of epidemiology, pathophysiology, and EEG monitoring of SE, and there have been large-scale treatment trials, discussed in this review.

Recent findings
Recent changes in the definitions of SE have helped guide management protocols and we have much better predictors of outcome. Observational studies have confirmed the efficacy of benzodiazepines and large treatment trials indicate that all routinely used second line treatments (i.e., levetiracetam, valproate and fosphenytoin) are equally effective. Better understanding of the pathophysiology has indicated that nonanti-seizure medications aimed at underlying pathological processes should perhaps be considered in the treatment of SE; already immunosuppressant treatments are being more widely used in particular for new onset refractory status epilepticus (NORSE) and Febrile infection-related epilepsy syndrome (FIRES) that sometimes revealed autoimmune or paraneoplastic encephalitis. Growing evidence for ICU EEG monitoring and major advances in automated analysis of the EEG could help intensivist to assess the control of electrographic seizures.

Summary
Research into the morbi-mortality of SE has highlighted the potential devastating effects of this condition, emphasizing the need for rapid and aggressive treatment, with particular attention to cardiorespiratory and neurological complications. Although we now have a good evidence-base for the initial status epilepticus management, the best treatments for the later stages are still unclear and clinical trials of potentially disease-modifying therapies are long overdue.
How to manage catatonia, Parkinson and dementia in ICU
Authors: Attali David , Calligaris Charlotte , Grabli David , Slooter Arjen J.C. 
Published: March 2024

Purpose of review
The rising prevalence of neurodegenerative and mental disorders, combined with the challenges posed by their frailty, has presented intensivists with complex issues in the intensive care unit (ICU). This review article explores specific aspects of care for patients with catatonia, Parkinson's disease (PD), and dementia within the context of the ICU, shedding light on recent developments in these fields.

Recent findings
Catatonia, a neuropsychiatric syndrome with potentially life-threatening forms, remains underdiagnosed, and its etiologies are diverse. PD patients in the ICU present unique challenges related to admission criteria, dopaminergic treatment, and respiratory care. Dementia increases the risk of delirium. Delirium is associated with long-term cognitive impairment and dementia.

Summary
While evidence is lacking, further research is needed to guide treatment for ICU patients with these comorbidities.
Acute encephalopathy in the ICU: a practical approach
Authors: Kurtz Pedro , van den Boogaard Mark , Girard Timothy D. , Hermann Bertrand 
Published: March 2024

Purpose of review
Acute encephalopathy (AE) – which frequently develops in critically ill patients with and without primary brain injury – is defined as an acute process that evolves rapidly and leads to changes in baseline cognitive status, ranging from delirium to coma. The diagnosis, monitoring, and management of AE is challenging. Here, we discuss advances in definitions, diagnostic approaches, therapeutic options, and implications to outcomes of the clinical spectrum of AE in ICU patients without primary brain injury.

Recent findings
Understanding and definitions of delirium and coma have evolved. Delirium is a neurocognitive disorder involving impairment of attention and cognition, usually fluctuating, and developing over hours to days. Coma is a state of unresponsiveness, with absence of command following, intelligible speech, or visual pursuit, with no imaging or neurophysiological evidence of cognitive motor dissociation. The CAM-ICU(−7) and the ICDSC are validated, guideline-recommended tools for clinical delirium assessment, with identification of clinical subtypes and stratification of severity. In comatose patients, the roles of continuous EEG monitoring and neuroimaging have grown for the early detection of secondary brain injury and treatment of reversible causes.

Summary
Evidence-based pharmacologic treatments for delirium are limited. Dexmedetomidine is effective for mechanically ventilated patients with delirium, while haloperidol has minimal effect of delirium but may have other benefits. Specific treatments for coma in nonprimary brain injury are still lacking.