bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurologic Complications of Patients With COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis
Authors: Li Cathy Meng Fei , Densy Deng Xiaoxiao , Ma Yu Fei , Dawson Emily , Li Carol , Wang Dong Yao , Huong Lynn , Gofton Teneille , Nagpal Atul Dave , Slessarev Marat 
Published: March 2023

OBJECTIVES:
In COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO), our primary objective was to determine the frequency of intracranial hemorrhage (ICH). Secondary objectives were to estimate the frequency of ischemic stroke, to explore association between higher anticoagulation targets and ICH, and to estimate the association between neurologic complications and in-hospital mortality.

DATA SOURCES:
We searched MEDLINE, Embase, PsycINFO, Cochrane, and MedRxiv databases from inception to March 15, 2022.

STUDY SELECTION:
We identified studies that described acute neurological complications in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring ECMO.

DATA EXTRACTION:
Two authors independently performed study selection and data extraction. Studies with 95% or more of its patients on venovenous or venoarterial ECMO were pooled for meta-analysis, which was calculated using a random-effects model.

DATA SYNTHESIS:
Fifty-four studies (n = 3,347) were included in the systematic review. Venovenous ECMO was used in 97% of patients. Meta-analysis of ICH and ischemic stroke on venovenous ECMO included 18 and 11 studies, respectively. The frequency of ICH was 11% (95% CI, 8–15%), with intraparenchymal hemorrhage being the most common subtype (73%), while the frequency of ischemic strokes was 2% (95% CI, 1–3%). Higher anticoagulation targets were not associated with increased frequency of ICH (p = 0.06). In-hospital mortality was 37% (95% CI, 34–40%) and neurologic causes ranked as the third most common cause of death. The risk ratio of mortality in COVID-19 patients with neurologic complications on venovenous ECMO compared with patients without neurologic complications was 2.24 (95% CI, 1.46–3.46). There were insufficient studies for meta-analysis of COVID-19 patients on venoarterial ECMO.

CONCLUSIONS:
COVID-19 patients requiring venovenous ECMO have a high frequency of ICH, and the development of neurologic complications more than doubled the risk of death. Healthcare providers should be aware of these increased risks and maintain a high index of suspicion for ICH.
Characteristics and Outcomes of ICU Patients Without COVID-19 Infection—Pandemic Versus Nonpandemic Times: A Population-Based Cohort Study
Authors: Leafloor Cameron W. , Imsirovic Haris , Qureshi Danial , Milani Christina , Nyarko Kwadjo , Dickson Sarah E. , Thompson Laura , Tanuseputro Peter , Kyeremanteng Kwadwo 
Published: March 2023

IMPORTANCE:
Outcomes for critically ill COVID-19 are well described; however, the impact of the pandemic on critically ill patients without COVID-19 infection is less clear.

OBJECTIVES:
To demonstrate the characteristics and outcomes of non-COVID patients admitted to an ICU during the pandemic, compared with the previous year.

DESIGN:
A population-based study conducted using linked health administrative data comparing a cohort from March 1, 2020, to June 30, 2020 (pandemic) to a cohort from March 1, 2019, to June 30, 2019 (nonpandemic).

SETTING AND PARTICIPANTS:
Adult patients (18 yr old) admitted to an ICU in Ontario, Canada, without a diagnosis of COVID-19 during the pandemic and nonpandemic periods.

MAIN OUTCOMES AND MEASURES:
The primary outcome was all-cause in-hospital mortality. Secondary outcomes included hospital and ICU length of stay, discharge disposition, and receipt of resource intensive procedures (e.g., extracorporeal membrane oxygenation, mechanical ventilation, renal replacement therapy, bronchoscopy, feeding tube insertion, and cardiac device insertion). We identified 32,486 patients in the pandemic cohort and 41,128 in the nonpandemic cohort. Age, sex, and markers of disease severity were similar. Fewer patients in the pandemic cohort were from long-term care facilities and had fewer cardiovascular comorbidities. There was an increase in all-cause in-hospital mortality among the pandemic cohort (13.5% vs 12.5%; p < 0.001) representing a relative increase of 7.9% (adjusted odds ratio, 1.10; 95% CI, 1.05–1.56). Patients in the pandemic cohort admitted with chronic obstructive pulmonary disease exacerbation had an increase in all-cause mortality (17.0% vs 13.2%; p = 0.013), a relative increase of 29%. Mortality among recent immigrants was higher in the pandemic cohort compared with the nonpandemic cohort (13.0% vs 11.4%; p = 0.038), a relative increase of 14%. Length of stay and receipt of intensive procedures were similar.

CONCLUSIONS AND RELEVANCE:
We found a modest increase in mortality among non-COVID ICU patients during the pandemic compared with a nonpandemic cohort. Future pandemic responses should consider the impact of the pandemic on all patients to preserve quality of care.
Which characteristics are associated with changes in medication status for lower urinary tract symptoms among patients with prostate cancer receiving external beam radiotherapy?
Authors: Kyoda Yuki , Hashimoto Kohei , Takahashi Atsushi , Maehana Takeshi , Tachikawa Kimihito , Muranaka Takashi , Kato Shuichi , Kurisu Tomoyo , Fukuta Fumimasa , Kirisawa Takahiro , Okada Manabu , Kobayashi Ko , Tanaka Toshiaki , Hinotsu Shiro , Masumori Naoya 
Published: March 2023

Abstract

Background
We clarified the predictive factors for changes in the status of medications for lower urinary tract symptoms (LUTS) 2 years after local radiotherapy for nonmetastatic prostate cancer.

Materials and methods
We retrospectively included patients who underwent local external radiotherapy for nonmetastatic prostate cancer in 8 institutions between April 2001 and March 2016. Patients were divided into the medication and no-medication group based on the use of drugs for LUTS before radiotherapy. We defined improvement of LUTS as when the patient did not require medication for LUTS at 24 months after radiotherapy in the medication group and as deterioration when medication was required in the no-medication group. Logistic regression analysis was used to evaluate predictive factors for changes in medication status.

Results
Altogether, 505 patients were divided into a no-medication group (n = 352) and a medication group (n = 153). The number of patients with deterioration and improvement in LUTS was 49 (14%) and 36 (23%), respectively. In the multivariate analysis, the predictive variables for deterioration were the International Prostate Symptom Score (≥8; odds ratio [OR], 2.21; p = 0.014) and the biopsy Gleason score (≤3 + 4 = 7; OR, 2.430; p = 0.008) in the no-medication group, whereas those for improvement were age (<75 years old; OR, 5.81; p = 0.002), the quality of life score (<3; OR, 3.15; p = 0.028), and a positive biopsy core rate (≥50%; OR, 2.530; p = 0.027) in the medication group.

Conclusions
These predictive factors for changes in the status of medications for LUTS at 2 years after external radiotherapy may help determine the definitive therapy for nonmetastatic prostate cancer.
Effect of Different Types and Dosages of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Lipoprotein(a) Levels: A Network Meta-analysis
Authors: Yu Zongliang , Hu Lanqing , Sun Changxin , Wang Zeping , Zhang Xiaonan , Wu Min , Liu Longtao 
Published: March 2023

Abstract:
Lipoprotein(a) [Lp(a)] has become an important component of the residual risk of cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors display promising effects in controlling Lp(a) levels. However, the effects of different types and dosages of PCSK9 inhibitors on Lp(a) have not been studied in detail. These include 2 monoclonal antibodies, alirocumab and evolocumab, and inclisiran, a small interfering RNA. We searched PubMed, Web of Science, Embase, and Cochrane Library for randomized controlled trials to investigate the efficacy of PCSK9 inhibitors at the Lp(a) level. Although changes in Lp(a) levels were not the primary endpoint in any of these studies, they all described these valuable data. Forty-one randomized controlled trials with 17,601 participants were included, involving 23 unduplicated interventions. Most PCSK9 inhibitors significantly reduced Lp(a) levels compared with placebo. The pairwise comparison demonstrated no significant difference among most PCSK9 inhibitors. However, in the comparison among different dosages of alirocumab, the dosage of 150 mg Q2W showed a significant reduction in Lp(a) levels compared with the dosages of 150, 200, and 300 mg Q4W. In addition, the comparison results demonstrated the significant efficacy of evolocumab 140 mg Q2W compared with alirocumab at a dosage of 150 mg Q4W. The cumulative rank probabilities demonstrated that evolocumab 140 mg Q2W showed the highest efficacy. This study showed that PCSK9 inhibitors reduced Lp(a) levels by up to 25.1%. A biweekly dose of either 140 mg evolocumab or 150 mg alirocumab was the best treatment option. However, the reduction in Lp(a) levels with a single kind of PCSK9 inhibitor alone did not demonstrate sufficient clinical benefit. Therefore, for patients with very high Lp(a) levels who remain at high residual risk in the context of statin administration, it may be acceptable to use a kind of PCSK9 inhibitor, but the clinical benefit needs further investigation.
Declining rates of opioid/acetaminophen combination product overdose: 2011–2020
Authors: Harris Elizabeth , Harms Michael , Cao Dazhe , Prestwood Courtney , DeBinya Lister , Kleinschmidt Kurt , Young Amy , Saha Srishti , Rule Jody , Alvarez Kristin , Das Sandeep R. , Lee William M. 
Published: March 2023

Background:
During the opioid epidemic, misuse of acetaminophen-opioid products resulted in supratherapeutic acetaminophen ingestions and cases of hepatotoxicity. In 2014, the US Food and Drug Administration (FDA) limited the amount of acetaminophen in combination products to 325 mg, and the US Drug Enforcement Administration (DEA) changed hydrocodone/acetaminophen from schedule III to schedule II. This study assessed whether these federal mandates were associated with changes in acetaminophen-opioid supratherapeutic ingestions.

Methods:
We identified emergency department encounters at our institution of patients with a detectable acetaminophen concentration and manually reviewed these charts.

Results:
We found a decline in acetaminophen-opioid supratherapeutic ingestions after 2014. A downtrend in hydrocodone/acetaminophen ingestions accompanied a relative increase in codeine/acetaminophen ingestions from 2015 onwards.

Conclusion:
This experience at one large safety net hospital suggests a beneficial impact of the FDA ruling in reducing likely unintentional acetaminophen supratherapeutic ingestions, carrying a risk of hepatotoxicity, in the setting of intentional opioid ingestions.
Stage migration as a surrogate of survival in hepatocellular carcinoma treated with transarterial chemoembolization
Authors: Kassab Ihab , Singal Amit G. , Ali Aamir , Narasimman Manasa , Arvind Ashwini , Ahmed Muneeb , Joshi Sagar , Manzoor Komal , Rich Nicole , Chen Vincent L , Zhao Zhe , Sarwar Ammar , Parikh Neehar D. 
Published: March 2023

Background & Aims:
Locoregional therapies, including transarterial chemoembolization (TACE), are recommended for the treatment of HCC; however, clinical trials evaluating their effectiveness have been complicated by a lack of validated surrogate outcomes. We aimed to evaluate if stage migration could serve as a potential surrogate of overall survival in patients undergoing TACE.

Approach:
We conducted a retrospective cohort study of adult patients with HCC who underwent TACE as initial therapy from 3 centers in the US from 2008 to 2019. The primary outcome was overall survival from the date of the first TACE treatment, and the primary exposure of interest was Barcelona Clinic Liver Cancer stage migration to a more advanced stage within 6 months of TACE. Survival analysis was completed using Kaplan-Meier and multiple Cox proportional hazard models adjusted by the site.

Results:
Of 651 eligible patients (51.9% Barcelona Clinic Liver Cancer stage A and 39.6% stage B), 129 (19.6%) patients experienced stage migration within 6 months of TACE. Those with stage migration had larger tumors (5.6 vs. 4.2 cm, p < 0.01) and higher AFP levels (median 92 vs. 15 ng/mL, p < 0.01). In multivariate analysis, stage migration was significantly associated with worse survival (HR: 2.82, 95% CI: 2.66–2.98), with a median survival of 8.7 and 15.9 months in those with and without stage migration. Other predictors of worse survival included the White race, higher AFP levels, a higher number of tumors, and a larger maximum HCC diameter.

Conclusion:
Stage migration is associated with increased mortality after TACE in patients with HCC and could serve as a surrogate end point in clinical trials evaluating locoregional therapies such as TACE.
Alcohol-induced tubulin post-translational modifications directly alter hepatic protein trafficking
Authors: Adhikari Raghabendra , Mitra Ramyajit , Bennett Robert G. , McVicker Benita L. , Tuma Pamela L. 
Published: March 2023

Background:
Chronic ethanol exposure leads to enhanced protein acetylation and acetaldehyde adduction. Of the multitude of proteins that are modified on ethanol administration, tubulin is among the best studied. However, an open question is whether these modifications are observed in patient samples. Both modifications have also been implicated in promoting alcohol-induced defects in protein trafficking, but whether they do so directly is also unanswered.

Methods and Results:
We first confirmed that tubulin was hyperacetylated and acetaldehyde-adducted in the livers from ethanol-exposed individuals to a similar extent as observed in the livers from ethanol-fed animals and hepatic cells. Livers from individuals with nonalcohol-associated fatty liver showed modest increases in tubulin acetylation, whereas nonalcohol-associated fibrotic human and mouse livers showed virtually no tubulin modifications. We also asked whether tubulin acetylation or acetaldehyde adduction can directly explain the known alcohol-induced defects in protein trafficking. Acetylation was induced by overexpressing the α-tubulin–specific acetyltransferase, αTAT1, whereas adduction was induced by directly adding acetaldehyde to cells. Both αTAT1 overexpression and acetaldehyde treatment significantly impaired plus-end (secretion) and minus-end (transcytosis)–directed microtubule-dependent trafficking and clathrin-mediated endocytosis. Each modification led to similar levels of impairment as observed in ethanol-treated cells. The levels of impairment by either modification showed no dose dependence or no additive effects suggesting that substoichiometric tubulin modifications lead to altered protein trafficking and that lysines are not selectively modified.

Conclusions:
These results not only confirm that enhanced tubulin acetylation is observed in human livers but that it is most relevant to alcohol-induced injury. Because these tubulin modifications are associated with altered protein trafficking that alters proper hepatic function, we propose that changing the cellular acetylation levels or scavenging free aldehydes are feasible strategies for treating alcohol-associated liver disease.
Adherence of those With Self-Reported Glaucoma in the United States to Eye Examination Visits
Authors: Hou Chiun-Ho , Shih Shu-Fang , Pu Christy 
Published: March 2023

Précis:
The adherence of American patients with self-reported glaucoma to the follow-up recommendations is extremely low. Estimated adherence rate is lower than that obtained by previous studies that did not use a US nationally representative sample.

Purpose:
To evaluate adherence to ophthalmic outpatient follow-up visits and vision examinations in the American population aged 40 years or above.

Methods:
The percentage of American patients aged≥40 years who adhered to glaucoma treatment guidelines was estimated using 2015–2019 Medical Expenditure Panel Survey (MEPS) data. Adherence was defined according to the International Council of Ophthalmology guidelines. We also compared individuals with and without self-reported glaucoma who have made at least one ophthalmic outpatient visit and at least 1 vision examination visit within a year. Differences in means and percentages were estimated to account for the covariance due to the complex sampling design.

Results:
Approximately 4.4 million people aged or above 40 years had self-reported glaucoma in 2019 (3.21%). The rate of prevalence significantly differed with race, with Black people having the highest prevalence in all studied years. Only 7.1% (95% CI: 0.049–0.102) and 2.67% (95% CI: 0.0137–0.0519) of this population underwent at least 1 ophthalmic outpatient examination or 1 vision examination per year. Older age, never married status, higher education, eye conditions, and diabetes were significantly associated with a higher probability of ophthalmic health care use.

Conclusions:
Adherence to follow-up among patients with self-reported glaucoma in this population-level study was lower than that in previously reported American, non-nationally representative studies. Barriers to adherence at the population level should be assessed to inform the design of future policy or program interventions.
Human pain ratings to electrical sinusoids increase with cooling through a cold-induced increase in C-fibre excitability
Authors: Pakalniskis Julius , Soares Sabrina , Rajan Suhasini , Vyshnevska Alina , Schmelz Martin , Solinski Hans Jürgen , Rukwied Roman , Carr Richard 
Published: March 2023

Abstract
Low-frequency sinusoidal current applied to human skin evokes local axon reflex flare and burning pain, indicative of C-fibre activation. Because topical cooling works well as a local analgesic, we examined the effect of cooling on human pain ratings to sinusoidal and rectangular profiles of constant current stimulation. Unexpectedly, pain ratings increased upon cooling the skin from 32 to 18°C. To explore this paradoxical observation, the effects of cooling on C-fibre responses to stimulation with sinusoidal and rectangular current profiles were determined in ex vivo segments of mouse sural and pig saphenous nerve. As expected by thermodynamics, the absolute value of electrical charge required to activate C-fibre axons increased with cooling from 32°C to 20°C, irrespective of the stimulus profile used. However, for sinusoidal stimulus profiles, cooling enabled a more effective integration of low-intensity currents over tens of milliseconds resulting in a delayed initiation of action potentials. Our findings indicate that the paradoxical cooling–induced enhancement of electrically evoked pain in people can be explained by an enhancement of C-fibre responsiveness to slow depolarization at lower temperatures. This property may contribute to symptoms of enhanced cold sensitivity, especially cold allodynia, associated with many forms of neuropathic pain.
Endoscopic retrograde cholangiopancreatography-oriented surgery for accomplished treatment of Mirizzi syndrome: a single-center experience
Authors: Karaahmet Fatih , Kekilli Murat 
Published: March 2023

Background
Mirizzi syndrome is a gallstone disease characterized by compression of extrahepatic biliary duct with an impacted stone. Our aim is to identify and describe the incidence, clinical presentation, operative details and the association postoperative complication of Mirizzi syndrome in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).

Methods
The ERCP procedures were held in Gastroenterology Endoscopy Unit and retrospectively evaluated. The patients were divided into two groups, the cholelithiasis + common bile duct (CBD) stone group and the Mirizzi syndrome group. These groups were compared with the demographic characteristics, ERCP procedures, types of Mirizzi syndrome and surgical technique.

Results
A total of 1018 consecutive patients who underwent ERCP were scanned retrospectively. Of the 515 patients fulfilling the criteria for ERCP, 12 had Mirizzi syndrome and 503 had cholelithiasis and CBD stones. Half of the Mirizzi syndrome patients were diagnosed with pre-ERCP ultrasonography. The mean diameter of choledoc was found to be 10 mm in ERCP. ERCP-related complication rates (pancreatitis, bleeding and perforation) were the same in the two groups; 66.6% of the Mirizzi syndrome patients applied cholecystectomy and placement of T-tube surgical procedures, and there were no postoperative complications.

Conclusion
Surgery is the definitive treatment of Mirizzi syndrome. Thus patients should have a correct preoperative diagnosis for an appropriate and safe surgery. We think that ERCP could be the best guide for this. Also, we believe that intraoperative cholangiography with ERCP and hybrid procedures for guiding surgical treatment may become an advanced treatment option in the future.
Accuracy and concordance of two-dimensional shear-wave elastography using transient elastography as the reference in chronic viral hepatitis and HIV infection in Rio de Janeiro, Brazil
Authors: Coelho Mariana , Fernandes Flavia , Cardoso Sandra W. , Piedade Juliana , Torres da Silva Marcos Vinícius , Santos Ricardo , Veloso Valdilea G. , Grinsztejn Beatriz , Pereira Gustavo Henrique , Perazzo Hugo 
Published: March 2023

Objectives
Evaluate the accuracy and agreement of two-dimensional shear-wave elastography (2D-SWE) LOGIQ-S8 with transient elastography in patients from Rio de Janeiro, Brazil.

Method
This retrospective study compared liver stiffness measurements (LSMs) using transient elastography (M and XL probes) and 2D-SWE GE-LOGIQ-S8 performed by a single experienced operator on the same day in 348 consecutive individuals with viral hepatitis or HIV infection. Suggestive and highly suggestive compensated-advanced chronic liver disease (c-ACLD) were defined by transient elastography-LSM ≥10 kPa and ≥15 kPa, respectively. Agreement between techniques and accuracy of 2D-SWE using transient elastography-M probe as the reference was assessed. Optimal cut-offs for 2D-SWE were identified using the maximal Youden index.

Results
Three hundred five patients [61.3% male, median age = 51 [interquartile range (IQR), 42–62] years, 24% with hepatitis C virus (HCV) ± HIV; 17% with hepatitis B virus (HBV) ± HIV; 31% were HIV mono-infected and 28% had HCV ± HIV post-sustained virological response] were included. The overall correlation (Spearman’s ρ) was moderate between 2D-SWE and transient elastography-M (ρ = 0.639) and weak between 2D-SWE and transient elastography-XL (ρ = 0.566). Agreements were strong (ρ > 0.800) in people with HCV or HBV mono-infection, and poor in HIV mono-infected (ρ > 0.400). Accuracy of 2D-SWE for transient elastography-M ≥ 10 kPa [area under the receiver operating characteristic (AUROC) = 0.91 (95% confidence interval [CI], 0.86–0.96); optimal cut-off = 6.4 kPa, sensitivity = 84% (95% CI, 72–92), specificity = 89% (95% CI, 84–92)] and for transient elastography-M ≥ 15 kPa [AUROC = 0.93 (95% CI, 0.88–0.98); optimal cut-off = 7.1 kPa; sensitivity = 91% (95% CI, 75–98), specificity = 89% (95% CI, 85–93)] were excellent.

Conclusion
2D-SWE LOGIQ-S8 system had a good agreement with transient elastography and an excellent accuracy to identify individuals at high risk for c-ACLD.