bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of HTK-Custodiol and St-Thomas solution as cardiac preservation solutions on early and midterm outcomes following heart transplantation
Authors: Dulguerov Filip , Abdurashidowa Tamila , Christophel-Plathier Emeline , Ion Lucian , Gunga Ziyad , Rancati Valentina , Yerly Patrick , Tozzi Piergiorgio , Albert Adelin , Ltaief Zied , Rotman Samuel , Meyer Philippe , Lefol Karl , Hullin Roger , Kirsch Matthias
Published: May 2024

OBJECTIVES

The choice of the cardiac preservation solution for myocardial protection at time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm heart transplantation (HTx) outcomes. We retrospectively compared our adult HTx performed with 2 different solutions, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score.

METHODS

From January 2009 to December 2020, 154 consecutive HTx of adult patients, followed up in pre- and post-transplantation by 2 different tertiary centres, were performed at the University Hospital of Lausanne, Switzerland. From 2009 to 2015, the cardiac preservation solution used was exclusively St-Thomas, whereafter an institutional decision was made to use HTK-Custodiol only. Patients were classified in 2 groups accordingly.

RESULTS

There were 75 patients in the St-Thomas group and 79 patients in the HTK-Custodiol group. The 2 groups were comparable in terms of preoperative and intraoperative characteristics. Postoperatively, compared to the St-Thomas group, the Custodiol group patients showed significantly lower inotropic scores [median (interquartile range): 35.7 (17.5–60.2) vs 71.8 (31.8–127), P < 0.001], rejection scores [0.08 (0.0–0.25) vs 0.14 (0.05–0.5), P = 0.036] and 30-day mortality rate (2.5% vs 14.7%, P = 0.007) even after adjusting for potential confounders. Microscopic analysis of the endomyocardial biopsies also showed less specific histological features of subendothelial ischaemia (3.8% vs 17.3%, P = 0.006). There was no difference in primary graft dysfunction requiring postoperative extracorporeal membrane oxygenation. The use of HTK-Custodiol solution significantly improved midterm survival (Custodiol versus St-Thomas: hazard ratio = 0.20, 95% confidence interval: 0.069–0.60, P = 0.004).

CONCLUSIONS

This retrospective study comparing St-Thomas solution and HTK-Custodiol as myocardial protection during heart procurement showed that Custodiol improves outcomes after HTx, including postoperative inotropic score, rejection score, 30-day mortality and midterm survival.
Natural history and complications of normocalcemic hyperparathyroidism: a retrospective cohort study
Authors: Hoong Caroline Wei Shan , Broski Stephen M , Sfeir Jad G , Clarke Bart Lyman
Published: May 2024

Normocalcemic hyperparathyroidism (NHPT) is variably defined, and information regarding complications and natural history are scarce. We aimed to describe the phenotype of NHPT in relation to hypercalcemic hyperparathyroidism (PHPT) and controls, to determine risk of progression, and to develop a predictive model for progression to PHPT. This is a retrospective chart review of 232 patients at a tertiary medical center, comparing 75 controls, 73 patients with NHPT, and 84 with PHPT. NHPT was intermediate in biochemical profile between controls and PHPT with respect to cCa, iPTH, intraindividual coefficient of variant of cCa, phosphorus, and 25(OH)D. NHPT patients had an increased adjusted risk of urolithiasis (OR 5.34, 95%CI, 2.41-12.71, P < .001) and fragility fractures (OR 4.53, 95%CI, 1.63-14.84, P = .006) versus controls, after adjustment for age, sex, and BMI. Fewer NHPT compared with PHPTH patients achieved cure with parathyroidectomy (P = .001). NHPT more often had nonlocalizing imaging or polyglandular disease (P = .005). Parathyroidectomy improved biochemical but not BMD parameters in NHPT. Over a median follow-up of 4.23 (IQR 1.76-5.31) years, NHPT patients managed expectantly experienced no change in iPTH, and progression to PHPT occurred in 9%. An XGBoost model combining 6 factors for progression (mean index 2 iPTH, mean index 2 cCa, 24-h urinary calcium, age, 25(OH)D, and presence of urolithiasis) had an area under the curve 1.00 (95%CI, 1.00-1.00, P < .001) for predicting combined progression. NHPT is a mild variant of PHPT at intermediate risk of urolithiasis and fragility fractures. Cure was less often achieved with parathyroidectomy, which did not improve BMD parameters. Progression was infrequent with conservative management. Because only a minority progressed to PHPT, in addition to lower surgical success rates, we suggest conservative management for the majority of NHPT unless risk factors for progression are identified.
Real-time inverse kinematics for robotic manipulation under remote center-of-motion constraint using memetic evolution
Authors: Davila Ana , Colan Jacinto , Hasegawa Yasuhisa
Published: May 2024

Robotic manipulation in surgical applications often demands the surgical instrument to pivot around a fixed point, known as remote center of motion (RCM). The RCM constraint ensures that the pivot point of the surgical tool remains stationary at the incision port, preventing tissue damage and bleeding. Precisely and efficiently controlling tool positioning and orientation under this constraint poses a complex Inverse Kinematics (IK) problem that must be solved in real-time to ensure patient safety and minimize complications. To address this problem, we propose PivotIK, an efficient IK solver that combines efficient evolutionary exploration with multi-objective Jacobian-based optimization. PivotIK can track desired tool poses accurately while satisfying the RCM constraint in real-time. We evaluated PivotIK through simulations and real-world experiments using redundant robotic manipulators with multi-degree-of-freedom surgical instruments. We compare PivotIK with other IK solvers in terms of solve rates, computation times, tracking errors, and RCM errors under various scenarios, including unconstrained and RCM-constrained trajectories. Our results show that PivotIK achieves superior performance, solving the IK problem in less than 1 ms with errors below 0.01 and 0.1 mm for tracking and RCM, respectively. Our real-world experiments confirm the effectiveness of PivotIK in ensuring smooth trajectory tracking and RCM compliance. PivotIK offers a promising solution for real-time IK for robotic manipulation under RCM constraints in surgical applications.
Environmental Constitutionalism in China: A Constitution without Constitutionalism?
Authors: Wang Evelyn Li
Published: May 2024

There is a long tradition of constitutionalising environmental protection in the People's Republic of China ('China'). This is illustrated, for example, by the constitutionalisation of the need to construct ‘ecological civilisation’ – a set of values and development concepts included in 2018 as part of constitutional amendments. Yet, the Constitution of China is often described as a constitution without constitutionalism. This article examines the constitutional environmental provisions in China, as well as the underpinning constitutional theories, to demonstrate how China enjoys environmental constitutionalism. This version of constitutionalism, however, is absent of rights and overwhelmingly enforced through state-based approaches, which means that it is distinct from the rights-based and courts-centred versions of liberal constitutionalism. This study thus exemplifies how constitutional practices may adopt different formulations and environmental constitutionalism exists without being committed to liberal principles.
Effects of Combination Antiretroviral Therapy and Nutritional Rehabilitation on Growth in Children Aged 6–36 Months with Severe Acute Malnutrition in IMPAACT Protocol P1092
Authors: Mmbaga Blandina Theophil , Ngocho James Samwel , Tierney Camlin , Ziemba Lauren , Reding Christina , Bone Frederic , Bradford Sarah , Costello Diane , Browning Renee , Moye John , Vhembo Tichaona , Mambiya Sharon , Msowoya Esnath , Owor Maxensia , Musoke Philippa
Published: May 2024

Background

Antiretroviral therapy (ART) is known to improve child survival and growth in children living with HIV (CLHIV). We investigated growth outcomes in children with severe nonedematous acute malnutrition (SAM) and without SAM (mild malnutrition and normal nutrition) after initiation of ART in both groups and nutritional support.

Material and Methods

IMPAACT P1092 enrolled CLHIV aged 6 to <36 months with World Health Organization (WHO)-defined SAM or without SAM across 5 sites in Sub-Saharan Africa and followed them for 48 weeks. The enrollment was conducted in four countries: Malawi, Tanzania, Uganda, and Zimbabwe between October 2015 and September 2017. Weight, height, and mid-upper arm circumference (MUAC) were measured at baseline through 48 weeks. WHO weight-for-length/height Z-scores (WFL/H Z-score) were calculated. SAM children received readily available therapeutic food per WHO guidelines. All participants were initiated on a triple-ART regimen. SAM children entered the study after initial nutritional rehabilitation.

Results

Fifty-two CLHIV, 25 in the SAM cohort and 27 in the without SAM cohort, were enrolled. WFL/H Z-scores and MUAC in the SAM cohort increased significantly at weeks 24 and 48 [WFL/H Z-scores: mean change (95% CI) 2.34 (1.77, 2.91) and 2.73 (2.09, 3.37), both P < .001; MUAC: mean change (95% CI) 2.63 (1.98, 3.28) and 3.53 (2.83, 4.24) cm, P < .001]. At week 48, mean SAM height was 4 cm shorter and mean weight 1 kg lighter than without SAM [post hoc mean differences −4.11 (95% CI −8.60, 0.38) cm and −0.92 (95% CI −2.22, 0.39) kg].

Conclusions

CLHIV with SAM who undergo WHO nutritional rehabilitation can achieve significant growth and WFL/H Z-score improvements but continued intensive anthropometric monitoring is needed as SAM may still be behind those without SAM.
A stable fixed-dose combination of benzalkonium chloride-free latanoprost and once-a-day timolol
Authors: Khopade Ajay J , Halder Arindam , Patel Vivek , Pateliya Bharat , Burade Vinod
Published: May 2024

Objective

This study outlines the development of a stable fixed dose combination solution formulation of Benzalkonium chloride-free latanoprost with once-a-day timolol in a gel-free reservoir vehicle.

Methods

A fixed-dose combination (FDC) formulation of latanoprost and timolol maleate was prepared by mixing polymers, buffers, and ionic preservatives followed by parylene coating of plastic bottles that were used for stability studies.

Key findings

The FDC formulation was a clear, colorless, slightly viscous solution. The adsorption of latanoprost on the parylene-coated plastic bottle surface was reduced. Promoting stability for 36 months. The assay and impurities and other physicochemical quality attributes, such as color, clarity, osmolality, and pH met the required standards of both latanoprost and timolol. The sterility and antimicrobial effectiveness testing also complied with the United States Pharmacopeia requirements. Stability was proven for 30 days in simulated in-use conditions. It showed clinically relevant (>2 mm Hg) intraocular pressure (IOP) reduction in a normotensive dog model. It also showed a higher IOP reduction (efficacy) over individual or concomitantly administered drug components and numerically better IOP reduction than the marketed FDC formulation in a conventional vehicle. Faster action was seen within 2-h on the first day and recovery took 5 days post-treatment cessation.

Conclusion

A stable FDC formulation in parylene-coated plastic bottles was successfully developed meeting the clinically relevant IOP reduction criteria. Comparable efficacy insptto existing treatment, this FDC is a preferable option for patients with conditions such as dry eye and ocular surface disease.
UCP1‐dependent brown adipose activation accelerates cardiac metabolic remodeling and reduces initial hypertrophic and fibrotic responses to pathological stress
Authors: Challa Azariyas A. , Vidal Pablo , Maurya Santosh K. , Maurya Chandan K. , Baer Lisa A. , Wang Yang , James Natasha Maria , Pardeshi Parth J. , Fasano Matthew , Carley Andrew N. , Stanford Kristin I. , Lewandowski E. Douglas
Published: May 2024

Brown adipose tissue (BAT) is correlated to cardiovascular health in rodents and humans, but the physiological role of BAT in the initial cardiac remodeling at the onset of stress is unknown. Activation of BAT via 48 h cold (16°C) in mice following transverse aortic constriction (TAC) reduced cardiac gene expression for LCFA uptake and oxidation in male mice and accelerated the onset of cardiac metabolic remodeling, with an early isoform shift of carnitine palmitoyltransferase 1 (CPT1) toward increased CPT1a, reduced entry of long chain fatty acid (LCFA) into oxidative metabolism (0.59 ± 0.02 vs. 0.72 ± 0.02 in RT TAC hearts, p < .05) and increased carbohydrate oxidation with altered glucose transporter content. BAT activation with TAC reduced early hypertrophic expression of β‐MHC by 61% versus RT‐TAC and reduced pro‐fibrotic TGF‐β1 and COL3α1 expression. While cardiac natriuretic peptide expression was yet to increase at only 3 days TAC, Nppa and Nppb expression were elevated in Cold TAC versus RT TAC hearts 2.7‐ and 2.4‐fold, respectively. Eliminating BAT thermogenic activation with UCP1 KO mice eliminated differences between Cold TAC and RT TAC hearts, confirming effects of BAT activation rather than autonomous cardiac responses to cold. Female responses to BAT activation were blunted, with limited UCP1 changes with cold, partly due to already activated BAT in females at RT compared to thermoneutrality. These data reveal a previously unknown physiological mechanism of UCP1‐dependent BAT activation in attenuating early cardiac hypertrophic and profibrotic signaling and accelerating remodeled metabolic activity in the heart at the onset of cardiac stress.
How Do Learners Receive Feedback on Note Writing? A Scoping Review
Authors: Hansen Allison , Klute Ryan M. , Yadav Manajyoti , Bansal Saurabh , Bond William F.
Published: May 2024

Purpose

The literature assessing the process of note-writing based on gathered information is scant. This scoping review investigates methods of providing feedback on learners’ note-writing abilities.

Method

Scopus and Web of Science were searched for studies that investigated feedback on student notes or reviewed notes written on an information or data-gathering activity in health care and other fields in August 2022. Of 426 articles screened, 23 met the inclusion criteria. Data were extracted on the article title, publication year, study location, study aim, study design, number of participants, participant demographics, level of education, type of note written, field of study, form of feedback given, source of the feedback, and student or participant rating of feedback method from the included articles. Then possible themes were identified and a final consensus-based thematic analysis was performed.

Results

Themes identified in the 23 included articles were as follows: (1) learners found faculty and peer feedback beneficial; (2) direct written comments and evaluation tools, such as rubrics or checklists, were the most common feedback methods; (3) reports on notes in real clinical settings were limited (simulated clinical scenarios in preclinical curriculum were the most studied); (4) feedback providers and recipients benefit from having prior training on providing and receiving feedback; (5) sequential or iterative feedback was beneficial for learners but can be time intensive for faculty and confounded by maturation effects; and (6) use of technology and validated assessment tools facilitate the feedback process through ease of communication and improved organization.

Conclusions

The various factors influencing impact and perception of feedback include the source, structure, setting, use of technology, and amount of feedback provided. As the utility of note-writing in health care expands, studies are needed to clarify the value of note feedback in learning and the role of innovative technologies in facilitating note feedback.
Lower Hounsfield Units at the Planned Lowest Instrumented Vertebra Is an Independent Risk Factor for Complications Following Adult Cervical Deformity Surgery
Authors: Williamson Tyler K. , Koslosky Ezekial J. , Lebovic Jordan , Owusu-Sarpong Stephane , Tretiakov Peter , Mir Jamshaid , Dave Pooja , Schoenfeld Andrew J. , Diebo Bassel G. , Koller Heiko , Lafage Renaud , Lafage Virginie , Passias Peter G.
Published: May 2024

Background:

The association of Hounsfield units (HU) and junctional pathologies in adult cervical deformity (ACD) surgery has not been elucidated.

Objective:

Assess if the bone mineral density of the LIV, as assessed by HUs, is prognostic for the risk of complications after ACD surgery.

Study Design/Setting:

Retrospective cohort study.

Methods:

HUs were measured on preoperative CT scans. Means comparison test assessed differences in HUs based on the occurrence of complications, linear regression assessed the correlation of HUs with risk factors, and multivariable logistic regression followed by a conditional inference tree derived a threshold for HUs based on the increased likelihood of developing a complication.

Results:

In all, 107 ACD patients were included. Thirty-one patients (29.0%) developed a complication (18.7% perioperative), with 20.6% developing DJK and 11.2% developing DJF. There was a significant correlation between lower LIVs and lower HUs (r=0.351, P=0.01), as well as age and HUs at the LIV. Age did not correlate with change in the DJK angle (P>0.2). HUs were lower at the LIV for patients who developed a complication and an LIV threshold of 190 HUs was predictive of complications (OR: 4.2, [1.2–7.6]; P=0.009).

Conclusions:

Low bone mineral density at the lowest instrumented vertebra, as assessed by a threshold lower than 190 Hounsfield units, may be a crucial risk factor for the development of complications after cervical deformity surgery. Preoperative CT scans should be routinely considered in at-risk patients to mitigate this modifiable risk factor during surgical planning.

Level of Evidence:

Level—III
Enhancing the management of locally advanced head and neck malignancies and cases with local/neck recurrence and metastasis through the integration of anlotinib with concurrent radiochemotherapy
Authors: Tie Xiaojing , Li Hang , Gao Ling , Liu Peijie , Gao Yaohong , Jin Mingxin , Duan Guangting , Yi Zhenying
Published: May 2024

The aim of this study is to assess the effectiveness and safety of anlotinib in conjunction with concurrent radiochemotherapy for the treatment of locally advanced head and neck malignant tumors, including cases exhibiting local or neck recurrence and metastasis. Between June 2020 and June 2023, 42 patients diagnosed with locally advanced head and neck malignant tumors or presenting with local or neck recurrence and metastasis were recruited. These individuals received treatment that combined anlotinib with concurrent radiochemotherapy, followed by a minimum of two cycles of oral anlotinib upon completion of the initial treatment regimen. Among the 19 patients diagnosed with nasopharyngeal carcinoma, 14 patients attained a complete response, while four patients achieved partial response, resulting in an overall response rate of 94.74% (18/19). Conversely, among the 23 patients with non-nasopharyngeal carcinoma, two patients achieved complete response and 16 attained partial response, yielding a response rate of 78.26% (18/23). The 6-month progression-free survival rate was 95.24%. After treatment, serum vascular endothelial growth factor receptor levels exhibited a significant decrease compared with pretreatment levels. Notably, no instances of treatment-related serious adverse reactions were recorded. The combination of anlotinib with concurrent radiochemotherapy demonstrates favorable efficacy in managing locally advanced head and neck malignant tumors, including instances of local or neck recurrence and metastasis. Furthermore, the treatment regimen is characterized by an acceptable safety profile and tolerability.
Clinician Prediction of Survival vs Calculated Prediction Scores in Patients Requiring Extracorporeal Membrane Oxygenation
Authors: Martin Laura Ann , Bojorquez Genesis R. , Yi Cassia , Ignatyev Alex , Pollema Travis , Davidson Judy E. , Odish Mazen
Published: May 2024

Background

Determining appropriate extracorporeal membrane oxygenation (ECMO) candidacy ensures appropriate utilization of this costly resource. The current ECMO survival prediction scores do not consider clinician assessment of patient viability. This study compared clinician prediction of survival to hospital discharge versus prediction scores.

Objectives

The aim of this study was to compare clinician prediction of patients' survival to hospital discharge versus prognostic prediction scores (Respiratory ECMO Survival Prediction [RESP] or Survival After Veno-Arterial ECMO [SAVE] score) to actual survival.

Methods

This was an observational descriptive study from January 2020 to November 2021 conducted with interviews of nurses, perfusionists, and physicians who were involved during the initiation of ECMO within the first 24 hours of cannulation. Data were retrieved from the medical record to determine prediction scores and survival outcomes at hospital discharge. Accuracy of clinician prediction of survival was compared to the RESP or SAVE prediction scores and actual survival to hospital discharge.

Results

Accurate prediction of survival to hospital discharge for veno-venous ECMO by nurses was 47%, 64% by perfusionists, 45% by physicians, and 45% by the RESP score. Accurate predictions of patients on veno-arterial ECMO were correct in 54% of nurses, 77% of physicians, and 14% by the SAVE score. Physicians were more accurate than the SAVE score, P = .021, and perfusionists were significantly more accurate than the RESP score, P = .044. There was no relationship between ECMO specialists' years of experience and accuracy of predications.

Conclusion

Extracorporeal membrane oxygenation clinicians may have better predictions of survival to hospital discharge than the prediction scores. Further research is needed to develop accurate prediction tools to help determine ECMO eligibility.
Effect of phospholipid curcumin Meriva on liver histology and kidney disease in nonalcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial
Authors: Musso Giovanni , Pinach Silvia , Mariano Filippo , Saba Francesca , De Michieli Franco , Framarin Luciana , Berrutti Mara , Paschetta Elena , Parente Renato , Lizet Castillo Yanina , Leone Nicola , Castellino Francesca , Cassader Maurizio , Gambino Roberto
Published: May 2024

Background and Aims:

NASH confers an increased liver-related and kidney morbidity. Phospholipid curcumin (Meriva) is a phospholipid formulation with ameliorated systemic curcumin absorption and delivery. We assessed the safety and efficacy of Meriva in NASH.

Approach and Results:

In this double-blind trial, 52 patients with biopsy-proven NASH (71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a chronic kidney disease) were randomized 1:1 to receive Meriva 2 g/d or placebo for 72 weeks. The primary endpoint was NASH resolution with no worsening of fibrosis. The secondary endpoints included a ≥1 stage liver fibrosis improvement with no NASH worsening; regression of significant (ie, stage ≥F2) fibrosis and CKD; and improvement in renal, glucose, lipid, and inflammatory parameters. We also explored the treatment effect on hepatic activation of NF-kB, a key proinflammatory transcription factor and a major target of curcumin. Fifty-one patients (26 on Meriva and 25 on placebo) completed the trial. Sixteen (62%) patients on Meriva versus 3 (12%) patients on placebo had NASH resolution (RR = 5.33 [95% CI = 1.76–12.13]; p = 0.003). Thirteen (50%) patients on Meriva versus 2 (8%) patients on placebo had ≥1 stage fibrosis improvement (RR = 6.50 [1.63–21.20]; p = 0.008). Eleven (42%) patients on Meriva versus 0 (0%) on placebo had regression of significant liver fibrosis (RR = 18.01 [1.43–36.07]; p = 0.02). Hepatic NF-kB inhibition predicted NASH resolution (AUC = 0.90, 95% CI = 0.84–0.95) and fibrosis improvement (AUC = 0.89, 95% CI = 0.82–0.96). Thirteen (50%) patients on Meriva versus 0 (0%) on placebo had chronic kidney disease regression (RR = 10.71 [1.94–17.99)]; p = 0.004). Compared with placebo, Meriva improved eGFR (difference in adjusted eGFR change: +3.59 [2.96–4.11] mL/min/1.73 m2/y, p = 0.009), fasting glucose(−17 mg/dL; 95% CI = −22, −12), HbA1c (−0.62%; 95% CI = −0.87%, −0.37%), LDL-C (−39 mg/dL; 95% CI = −45, −33), triglycerides (−36 mg/dL, 95% CI = −46, −26), HDL-C (+10 mg/dL; 95% CI = +8, +11), and inflammatory markers. Adverse events were rare, mild, and evenly distributed.

Conclusions:

In patients with NASH, Meriva administration for 72 weeks was safe, well-tolerated, and improved liver histology, possibly through NF-kB inhibition, kidney disease, and metabolic profile.
Moxifloxacin-associated acute pigment dispersion and iris transillumination after phakic lens surgery
Authors: Jones Marlee , Reynhout Julia , Schirber Scott , Khachikian Stephen
Published: May 2024

Introduction:

Acute pigment dispersion and elevated intraocular pressure (IOP) were found after phakic intraocular lens surgery where 0.5% moxifloxacin was used. While scattered reports can be found in the literature, to the authors' knowledge, this is the first time it has been linked to intracameral 0.5% moxifloxacin.

Patient and Clinical Findings:

A 23-year-old man experienced symptoms of unilateral eye pain, increased IOP, diffuse pigment dispersion, transillumination defects, and mydriasis after successful bilateral Starr Visian EVO implantable collamer lens implantation.

Diagnosis, Intervention and Outcomes:

Intracameral moxifloxacin (0.5%) was given at the time of the procedure and was suspected to be the cause of this patient's postoperative findings. These findings are consistent with iris toxicity associated with systemic moxifloxacin. Supportive care was given, however, the resulting pigment dispersion and mydriasis are permanent.

Conclusions:

Although generally safe for intracameral use, moxifloxacin has the potential to be toxic to the iris. Patients with phakia may be at higher risk of this toxicity, and lower concentrations of intracameral moxifloxacin should be considered in these patients.
Influence of chronotype on pain incidence during early adolescence
Authors: Li Rui , Groenewald Cornelius , Tham See Wan , Rabbitts Jennifer A. , Ward Teresa M. , Palermo Tonya M.
Published: May 2024

During adolescence major shifts in sleep and circadian systems occur with a notable circadian phase delay. Yet, the circadian influence on pain during early adolescence is largely unknown. Using 2 years of data from the Adolescent Brain Cognitive Development study, we investigated the impact of chronotype on pain incidence, moderate-to-severe pain, and multiregion pain 1 year later in U.S. adolescents. Based on the Munich ChronoType Questionnaire, chronotype was calculated as the midpoint between sleep onset and offset on free days, corrected for sleep debt over the week. Adolescents reported pain presence over the past month, and if present, rated pain intensity (0-10 numerical rating scale; ≥ 4 defined as moderate-to-severe pain) and body site locations (Collaborative Health Outcomes Information Registry Body Map; ≥2 regions defined as multiregion pain). Three-level random intercept logistic regression models were specified for each pain outcome, adjusting for baseline sociodemographic and developmental characteristics. Among 5991 initially pain-free adolescents (mean age 12.0 years, SD 0.7), the mean chronotype was 3:59 am (SD 97 minutes), and the 1-year incidence of pain, moderate-to-severe pain, and multiregion pain was 24.4%, 15.2%, and 13.5%, respectively. Each hour later chronotype at baseline was associated with higher odds of developing any pain (odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.01, 1.11), moderate-to-severe pain (OR = 1.10, 95% CI = 1.05-1.17), and multiregion pain (OR = 1.08, 95% CI = 1.02-1.14) during 1-year follow-up. In this diverse U.S. adolescent sample, later chronotype predicted higher incidence of new-onset pain.
The impact of von Willebrand factor on fibrin formation and structure unveiled with type 3 von Willebrand disease plasma
Authors: Martinez-Vargas Marina , Courson Justin , Gardea Luis , Sen Mehmet , Yee Andrew , Rumbaut Rolando , Cruz Miguel A.
Published: May 2024

Normally, von Willebrand factor (VWF) remains inactive unless its A1A2 domains undergo a shear stress-triggered conformational change. We demonstrated the capacity of a recombinant A2 domain of VWF to bind and to affect fibrin formation, altering the fibrin clot structure. The data indicated that VWF contains an additional binding site for fibrin in the A2 domain that plays a role in the incorporation of VWF to the polymerizing fibrin. This study is to examine the hypothesis that active plasma VWF directly influence fibrin polymerization and the structure of fibrin clots.

The study used healthy and type 3 von Willebrand disease (VWD) plasma, purified plasma VWF, fibrin polymerization assays, confocal microscopy and scanning electron microscopy.

The exposed A2 domain in active VWF harbors additional binding sites for fibrinogen, and significantly potentiates fibrin formation (P < 0.02). Antibody against the A2 domain of VWF significantly decreased the initial rate of change of fibrin formation (P < 0.002). Clot analyses revealed a significant difference in porosity between normal and type 3 VWD plasma (P < 0.008), further supported by scanning electron microscopy, which demonstrated thicker fibrin fibers in the presence of plasma VWF (P < 0.0003). Confocal immunofluorescence microscopy showed punctate VWF staining along fibrin fibrils, providing visual evidence of the integration of plasma VWF into the fibrin matrix.

The study with type 3 VWD plasma supports the hypothesis that plasma VWF directly influences fibrin polymerization and clot structure. In addition, a conformational change in the A1A2 domains exposes a hidden fibrin(ogen) binding site, indicating that plasma VWF determines the fibrin clot structure.
Hematological ratios in patients with acute decompensation and acute-on-chronic liver failure: prognostic factors
Authors: Lashen Sameh A. , Salem Perihan , Ibrahim Esraa , Abd Elmoaty Dalia , Yousif Walid I.
Published: May 2024

Background and aims

Acute-on-chronic liver failure (ACLF) is the most severe form of acutely decompensated cirrhosis and is characterized by the presence of intense systemic inflammation. Leucocyte quantification can serve as an indirect indicator of systemic inflammation. In our study, we investigated the predictive value of hematological ratios (neutrophils to lymphocytes, monocyte to lymphocytes, platelets to lymphocytes, lymphocytes to C-reactive protein, and neutrophils to lymphocytes and platelets) in acute decompensation (AD) and ACLF patients and their relation to disease severity and early mortality.

Patients and methods

We included 60 patients with ACLF and AD, and 30 cirrhotic controls. Clinical data were collected, and survival was followed for 1 and 6 months. Blood samples were analyzed at admission for differential leucocytes and assessed for liver and renal function tests. The leukocyte ratios were calculated and compared, and their correlation with liver function indicators and prognosis was assessed.

Results

All ratios were significantly higher in AD and ACLF patients compared to control (except for lymphocyte to C-reactive protein ratio which was significantly lower), and were positively correlated with Child-Pugh score, model for end-stage liver disease (MELD)-Na, and ACLF severity scores. Multivariate regression revealed that neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, and MELD-Na were independent prognostic factors of 1-month and 6-month mortality. A unique prognostic nomogram incorporating MELD-Na, neutrophil to lymphocyte ratio, and monocyte to lymphocyte ratio could be proposed for predicting prognosis in AD and ACLF patients.

Conclusions

Cheap, easy, and noninvasive hematological ratios are introduced as a tool for early identification and risk stratification of AD and ACLF patients.
Symptoms of functional dyspepsia and irritable bowel syndrome among medical students in Slovakia and their relation to diet and exercise
Authors: Liptak Peter , Duricek Martin , Schnierer Martin , Ziaciková Ivana Liptak , Rosolanka Robert , Baranovicova Eva , Sturdik Igor , Jackuliak Peter , Veseliny Eduard , Varady Alena , Banovcin Peter
Published: May 2024

Introduction

There is a substantial lack of data regarding the prevalence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) in the region of Central/Eastern Europe. It is a well-described and known fact that environmental, ethnic, dietary, and cultural factors can influence the reporting of symptoms. Therefore, we aim to provide the first data documenting the prevalence of specific disorders of gut-brain interaction in Slovakia.

Methods

This is a multicenter-based study. The study population consists of medical students from three medical faculties in Slovakia, mainly with Slovakian and Scandinavian permanent residency. Data collection was performed by means of anonymous questionnaires consisting of several demographic questions. Two forms of questionnaires were used. One was in paper form, and the second was distributed via email.

Results

Altogether, 1061 students participated in this study. Symptoms of IBS were presented in 7.3% of students, and FD in 13%. In the Slovakian group, these were FD 12%, and IBS 7%. The subgroup from Scandinavia shows a prevalence of IBS of 11.7% and FD of 14.0%. A lack of exercise and a vegan diet are related to a higher presence of FD.

Conclusion

The results of this multicentre study represent the first published data for the presence of symptoms of IBS and FD in Slovakia. Our data also show a significantly higher prevalence of IBS in students from Scandinavia compared with those from Central/Eastern Europe. A higher frequency of physical exercise is associated with a lower presence of symptoms of FD. On the other hand, the symptoms of FD were mostly prevalent in the group adhering to a vegan and vegetarian type diet.
Impacts of rifaximin and midodrine on morbidity, mortality, and quality of life in patients with decompensated liver cirrhosis
Authors: Elsabaawy Maha Mohammad , Assem Medhat , Badran Hanaa , Mahmoud Asmaa , Elsabaawy Dalia , Ragab Amr
Published: May 2024

Background

Vasodilatation and bacterial dislocation are the main contributors to the catastrophic events in patients with decompensated liver cirrhosis (DLC).

Aim

The aim of this study was to evaluate the impacts of adding midodrine and rifaximin on morbidity, mortality, and quality of life in patients with DLC.

Methods

This interventional clinical study included 100 consecutively enrolled DLC patients randomized 1 : 1 into two groups. Group A received oral midodrine (5 mg/8 h) and rifaximin (550 mg/12 h) with standard diuretic therapy, while group B received only standard diuretic therapy. Clinical and laboratory data, including the McGill Quality of Life Questionnaire, were evaluated over a 3-month treatment period.

Results

In the study group, there was a significant reduction in Child–Pugh and Model for End-Stage Liver Disease scores, international normalized ratio, and mean arterial blood pressure at 2, 6, and 12 weeks (P < 0.05). Ascites, spontaneous bacterial peritonitis incidence, hematemesis, paracentesis need, and hepatic encephalopathy showed improvement after 12 weeks compared with the control group. McGill Quality of Life Questionnaire significantly improved after 6 and 12 weeks (P < 0.05). Survival rates demonstrated a noteworthy improvement (P = 0.014), substantiated by evidence in both univariate and multivariate regression analyses.

Conclusion

Combined midodrine with rifaximin represents an endowment to patients with DLC with spectacular improvements in synthetic liver functions, along with improved quality of life, and survival.
Veno-Occlusive Disease: A Life-Saving Novel Approach With Plasma Exchange, IVIG, and Steroid, Without Defibrotide
Authors: Katlan Banu , Erkasar Funda , Topdemir Mesut , Günaydin Gulçin , Ozen Alptug
Published: May 2024

Introduction:

Hepatic veno-occlusive disease (VOD) is a critical medical emergency with a high mortality rate of up to 90% if not promptly treated. Defibrotide is the only approved medication for VOD treatment, exhibiting anti-inflammatory, antithrombotic, and anti-ischemic properties. This report presents a case of severe VOD in a patient undergoing acute lymphoblastic leukemia (ALL) treatment.

Case Presentation:

We describe the successful and rapid treatment of severe VOD in an ALL patient using therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and methylprednisolone (MPZ). The patient showed significant clinical and laboratory improvement after this combined therapeutic approach.

Conclusion:

This case highlights the effectiveness of TPE, IVIG, and MPZ in the treatment of severe VOD in ALL patients, providing insights into alternative therapeutic strategies in the absence of Defibrotide.
Comparing Leadership Skills of Senior Emergency Medicine Residents in 3-Year Versus 4-Year Programs During Simulated Pediatric Resuscitation
Authors: Schoppel Kyle , Keilman Ashley , Fayyaz Jabeen , Padlipsky Patricia , Diaz Maria Carmen G. , Wing Robyn , Hughes Mary , Franco Marleny , Swinger Nathan , Whitfill Travis , Walsh Barbara ,   Improving Pediatric Acute Care Through Simulation (ImPACTS)
Published: May 2024

Objectives

The majority of pediatric patients in the United States (US) are evaluated and treated at general emergency departments. It is possible that discrepancies in length of emergency medicine (EM) residency training may allow for variable exposure to pediatric patients, critical resuscitations, and didactic events. The goal of this pilot study was to compare leadership skills of graduating EM residents from 3- to 4-year programs during simulated pediatric resuscitations using a previously validated leadership assessment tool, the Concise Assessment of Leader Management (CALM).

Methods

This was a prospective, multicenter, simulation-based cohort pilot study that included graduating 3rd- and 4th-year EM resident physicians from 6 EM residency programs. We measured leadership performance across 3 simulated pediatric resuscitations (sepsis, seizure, cardiac arrest) using the CALM tool and compared leadership scores between the 3rd- and 4th-year resident cohorts. We also correlated leadership to self-efficacy scores.

Results

Data was analyzed for 47 participating residents (24 3rd-year residents and 23 4th-year residents). Out of a total possible CALM score of 66, residents from 3-year programs scored 45.2 [SD ± 5.2], 46.8 [SD ± 5.0], and 46.6 [SD ± 4.7], whereas residents from 4-year programs scored 45.5 [SD ± 5.2], 46.4 [SD ± 5.0], and 48.2 [SD ± 4.3] during the sepsis, seizure, and cardiac arrest cases, respectively. The mean leadership score across all 3 cases for the 3-year cohort was 46.2 [SD ± 4.8] versus 46.7 [SD ± 4.5] (P = 0.715) for the 4-year cohort.

Conclusions

These data show feasibility for a larger cohort project and, while not statistically significant, suggest no difference in leadership skills between 3rd- and 4th-year EM residents in our study cohort. This pilot study provides the basis of future work that will assess a larger multicenter cohort with the hope to obtain a more generalizable dataset.
Low Prevalence of Clinically Significant Hyponatremia following Cranial Vault Reconstruction for Single-Suture Craniosynostosis
Authors: Breuler Christopher , Lynn Jeremy V. , Buchman Lauren , Matusko Niki , Makar Katelyn , Ranganathan Kavitha , Mouch Charles , Muraszko Karin , Buchman Steven R.
Published: May 2024

Background:

Patients are commonly monitored for hyponatremia after intracranial procedures, yet the prevalence of hyponatremia after cranial vault reconstruction (CVR) remains unclear. The purpose of this study is to define the prevalence, risk factors, and complications of hyponatremia after CVR to optimize postoperative sodium surveillance protocols.

Methods:

Patients with nonsyndromic, single-suture craniosynostosis who underwent primary CVR between 2009 and 2020 at Michigan Medicine were included (n = 231). Demographic, intraoperative, and postoperative characteristics were compared by postoperative hyponatremia status at P < 0.05 significance. Hyponatremia was defined as mild (<135 mEq/L), moderate (<130 mEq/L), or severe (<125 mEq/L) based on the lowest postoperative laboratory draw.

Results:

Twenty-three patients (10.0%) developed mild postoperative hyponatremia. No patient developed moderate or severe postoperative hyponatremia. On multivariable regression, decreased preoperative sodium level (P = 0.03) and decreased preoperative weight (P = 0.02) were significantly associated with mild postoperative hyponatremia. No patient developed complications or required hospital readmission because of hyponatremia.

Conclusions:

This large retrospective cohort study of patients with nonsyndromic single-suture craniosynostosis demonstrated a 10% prevalence of mild, clinically inconsequential hyponatremia and 0% prevalence of moderate or severe, clinically significant hyponatremia after primary CVR. Patients with low preoperative sodium level or weight were at increased risk for developing mild postoperative hyponatremia. The results suggest that patients with preoperative sodium greater than 140 mEq/L or preoperative weight greater than 10 kg may be candidates for limited postoperative sodium surveillance; however, future prospective studies are warranted before implementation.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Simultaneous Injection of Contrast and Saline Using Spiral Flow-Generating Tube for Hepatic Dynamic Computed Tomography: Effect on Enhancement of Liver Parenchyma and Metastases to the Liver
Authors: Nagata Hiroji , Iori Hisako , Yoshida Shiori , Kawashima Hiroki , Nishino Yuka , Sakasai Ryo , Yamamura Hiroshi , Minami Tetsuya
Published: May 2024

Purpose

Recently, there have been a few reports regarding the usefulness of a novel saline injection technique using a spiral flow-generating tube. The purpose of this study was to evaluate whether simultaneous saline injection using a spiral flow-generating tube was able to improve hepatic contrast enhancement and lesion conspicuity of metastatic liver tumors.

Methods

We randomized a total of 411 patients with various liver diseases including metastases by total body weight (A, n = 204) and contrast dilution protocol (B, n = 207). Group A received 400 mgI/kg of contrast medium alone without a spiral flow-generating tube; group B received contrast medium 400 mgI/kg simultaneous with injection of a 0.57-ml/kg physiologic saline solution through a spiral flow-generating tube. Abdominal aorta computed tomography (CT) number, hepatic enhancement (ΔHU), percentage of tests demonstrating an enhancement effect of the liver parenchyma exceeding Δ50 HU in 3 measured segments (S2, S6, and S8), and the contrast-to-noise ratio of the metastatic liver tumors were measured.

Results

The mean aortic CT number of group B (417.0 HU ± 61.7; P < 0.01) was approximately 10% higher than that of group A (384.6 ± 79.1 HU). The average ΔHU was 59.8 ± 11.4 HU for group A and 61.7 ± 11.7 for group B. The ΔHU for group B was significantly higher than that for group A (P = 0.017). The percentage of tests demonstrating with the enhancement effect of group B was more than 80% in all subgroups; however, that of group A was less than 80% in all subgroups. The contrast-to-noise ratio of group B (7.8 ± 3.3 HU) was significantly higher compared to that of group A (6.5 ± 2.8 HU) (P < 0.05).

Conclusions

Because of the volume effect, injecting a contrast medium diluted with normal saline improved the degree of hepatic and aortic contrast enhancement and achieved better visualization of liver metastases.

Clinical Impact

The use of spiral flow-generating tube may help diagnostic of hepatic and aortic contrast enhancement and liver metastases.

Importance

The use of a spiral flow-generating tube improved the degree of hepatic and aortic contrast enhancement and achieve better visualization of liver metastases.

Points

The use of low-concentration syringe formulations is limited by body weight. However, the use of spiral flow-generating tube provides low-concentration contrast medium regardless of body weight
Cause Analysis and Surgical Treatment of Aponeurotic Ptosis With Upper Eyelid Depression
Authors: Hou Dan , Tian Bingyu , Wang Xiaoyu , Wang Qianyu , Zhu Yuan
Published: May 2024

Background:

Ptosis and upper eyelid depression were previously diagnosed as 2 separate diseases. The authors found that in patients with aponeurotic ptosis accompanied by upper eyelid depression, the main cause of upper eyelid depression was impaired dynamic transmission of the levator aponeurosis.

Objective:

To analyze the causes of upper eyelid depression in patients with aponeurotic ptosis accompanied by upper eyelid depression and to introduce the best treatment methods.

Methods:

The authors enrolled 15 eyes (11 patients) with aponeurotic ptosis accompanied by upper eyelid depression from October 2021 to August 2022. The authors analyzed the causes of upper eyelid depression in those patients and performed aponeurotic ptosis correction surgery and orbital septum fat release surgery. After 6 to 12 months of follow-up, the authors reviewed the patient’s medical records and photographs to evaluate the treatment outcomes.

Results:

After surgery, ptosis was corrected and upper eyelid depression significantly improved in all the patients. One patient had poor eyelid morphology and upper eyelid depression due to habitual brow lifting, which was relieved after an injection of botulinum toxin into the frontalis muscle. One patient had overcorrection of the upper eyelid depression on the affected side and no other complications.

Conclusion:

The main cause of upper eyelid depression in patients with aponeurotic ptosis is impaired dynamic transmission of the levator aponeurosis. Aponeurotic ptosis repair surgery and orbital septum fat release surgery are simple surgical procedures that restore the normal anatomy and physiology of the upper eyelid and maintain the normal structure of the eyelid, with good post-operative outcomes.
Biomechanical Analysis of Orbital Development: A Finite Element Analysis by an Experimentally Validated Model
Authors: Wang Mingyang , Jiang Xue , Song Dongyu , Li Dongmei
Published: May 2024

Aims:

Constructing orbital finite element models capable of simulating the development process and analyzing the biomechanical mechanism.

Methods:

Four normal orbits from 1-month-old New Zealand white rabbits were used in this study. Toshiba Aquilion Prime was used to determine the computed tomography scan and direct orbital pressure manometry using an improved manometer based on the TSD104 pressure sensor transducer. The finite element analysis was conducted using the ANSYS Workbench platform.

Results:

The biomechanics of each orbital wall improved to varying degrees as the rabbit orbit grew and developed. The von Mises stress in both rabbits initially concentrated at the lower edge of the posterior orbital wall, expanded to the entire orbit, and ultimately became more significant in the biomechanics of the region that consisted of the posterior orbital and superior orbital walls. During the expansion phase, the biomechanics of both rabbits gradually developed from the nasal side to the occipital side for radial displacement. It is evident that the finite element model is a good fit for simulating the physiological development of the rabbit orbit. The maximum radial displacement and maximum von Mises stress appeared 2 intermissions during the development of the orbit, at about 50 to 60 days and 80 to 90 days.

Conclusion:

This study establishes a theoretical foundation for the creation of a biomechanical model of human orbital development by offering the first finite element model to simulate orbital development and analyze the biomechanical mechanism of orbital pressure on orbital development.