bluuebunny/crossref_metadata_2025 huggingface dataset:
Poor outcomes for trial‐ineligible patients receiving polatuzumab for relapsed/refractory diffuse large B‐cell lymphoma in routine care: An Australian Lymphoma and Related Diseases Registry project
Authors: Shaw Briony , Chung Eliza , Wellard Cameron , Yoo Edward , Bennett Rory , Birks Callum , Johnston Anna , Cheah Chan Y , Hamad Nada , Simpson Jock , Barraclough Allison , Ku Matthew , Viiala Nicholas , Ratnasingam Sumita , Armytage Tasman , Cochrane Tara , Chong Geoffrey , Lee Denise , Manos Kate , Keane Colm , Wallwork Stephanie , Opat Stephen , Hawkes Eliza A.
Published: February 2024

Polatuzumab vedotin (Pola) is an approved therapy in combination with rituximab and bendamustine for relapsed or refractory diffuse large B‐cell lymphoma (RR‐DLBCL) based on positive results of the landmark phase II randomised G029365 trial. However, trial results for many approved novel therapies in RR‐DLBCL have not been replicated in routine care cohorts, as RR‐DLBCL patient populations are heterogeneous and trial eligibility is increasingly restrictive. We evaluated outcomes from pola ± bendamustine and rituximab in patients with RR‐DLBCL enrolled in a compassionate access program with no alternative treatment options identified via the Australasian Lymphoma and Related Diseases Registry according to their eligibility for the original phase II published study. Of 58 eligible patients, 74% met the criteria deeming them ineligible for the G029365 original study at the time of pola's commencement. Median progression‐free survival and overall survival in our cohort were 2.3 and 3.5 months, respectively. In contrast to the landmark trial cohort, more of our patients ceased therapy prior to completion, the majority due to progressive disease and only 8/58 received any subsequent treatment. Dismal outcomes in this Australian real‐world population demonstrate trial eligibility is challenging to meet, and newer treatments can be difficult to deliver in routine care. Clinically applicable results from therapeutic studies require trial cohorts to reflect representative clinical populations wherever possible, and more research is required to address the benefit of novel agents in the increasing majority who are ineligible for modern studies.
Utilizing fab fragment‐conjugated surface plasmon resonance‐based biosensor for detection of SalmonellaEnteritidis
Authors: Eser Esma , Ekiz Okan Öner , Ekiz H. İbrahim
Published: February 2024

Although antibodies, a key element of biorecognition, are frequently used as biosensor probes, the use of these large molecules can lead to adverse effects. Fab fragments can be reduced to allow proper antigen‐binding orientation via thiol groups containing Fab sites that can directly penetrate Au sites chemically. In this study, the ability of the surface plasmon resonance (SPR) sensor to detect Salmonella was studied. Tris(2‐carboxyethyl)phosphine was used as a reducing agent to obtain half antibody fragments. Sensor surface was immobilized with antibody, and bacteria suspensions were injected from low to high concentrations. Response units were changed by binding first reduced antibody fragments, then bacteria. The biosensor was able to determine the bacterial concentrations between 103 and 108 CFU/mL. Based on these results, the half antibody fragmentation method can be generalized for faster, label‐free, sensitive, and selective detection of other bacteria species.
Effects of Gadolinium Retention in the Brains of Type 2 Diabetic Rats after Repeated Administration of Gadolinium‐Based MRI Contrast Agents on Neurobiology and NLRP3 Inflammasome Activation
Authors: Yao Xiang , Zhang Haoran , Hu Jingyi , Lin Xiaoning , Sun Jin , Kang Junlong , Huang Zhichun , Wang Guangsong , Tian Xinhua , Chen E. , Ren Ke
Published: February 2024

Background

The neurotoxic potential of gadolinium (Gd)‐based contrast agents (GBCAs) retention in the brains of patients with type 2 diabetes mellitus (T2DM) is unclear.

Purpose

To determine the deposition and clearance of GBCAs in T2DM rats and the mechanism by which Gd enhances nucleotide‐binding oligomerization domain‐3 (NLRP3) inflammasome activation.

Study Type

Cross‐sectional, prospective.

Animal Model

104 T2DM male Wistar rats.

Field Strength/Sequence

9.4‐T, T1‐weighted fast spin echo sequence.

Assessment

T2DM (male Wistar rats, n = 52) and control group (healthy, male Wistar rats, n = 52) rats received saline, gadodiamide, Gd‐diethylenetriaminepentaacetic acid, and gadoterate meglumine for four consecutive days per week for 7 weeks. The distribution and clearance of Gd in the certain brain were assessed by MRI (T1 signal intensity and relaxation rate R1, on the last day of each week), inductively coupled plasma mass‐spectroscopy, ultraperformance liquid chromatography mass spectrometry, and transmission electron microscopy. Behavioral tests, histopathological features, and the effects of GBCAs on neuroinflammation were also analyzed.

Statistical Tests

One‐way analysis of variance, bonferroni method, and unpaired t‐test. A P‐value <0.05 was considered statistically significant.

Results

The movement distance and appearance time in the open field test of the T2DM rats in the gadodiamide group were significantly shorter than in the other groups. Furthermore, the expression of NLRP3, Pro‐Caspase‐1, interleukin‐1β (IL‐1β), and apoptosis‐associated speck‐like protein containing a CARD protein in neurons was significantly higher in the gadodiamide group than in the saline group, as shown by Western blot. Gadodiamide also induced differentiation of microglia into M1 type, decreased the neuronal mitochondrial membrane potential, and significantly increased neuronal apoptosis from flow cytometry.

Data Conclusion

T2DM may affect both the deposition and clearance of GBCAs in the brain. Informed by the T2DM model, gadodiamide could mediate the neuroinflammatory response by NLRP3 inflammasome activation.

Level of Evidence

1

Technical Efficacy

Stage 1
Single high‐energy arc proton therapy with Bragg peak boost (SHARP)
Authors: Penfold Scott N. , Santos Alexandre M. C. , Penfold Melanie , Shierlaw Emma , Crain Rosanna
Published: February 2024

Introduction

Because of the co‐location of critical organs at risk, base of skull tumours require steep dose gradients to achieve the prescribed dosimetric criteria. When available, proton beam therapy (PBT) is often considered a desirable modality for these cases, but in many instances, compromises in target coverage are still required to achieve critical organ at risk (OAR) tolerance doses. A number of techniques have been proposed to further improve the penumbra of PBT. In the current study, we propose a novel, collimator‐free treatment planning technique that combines high‐energy shoot‐through proton beams with conventional Bragg peak spot placement. The small spot size of the high‐energy pencil beams provides a sharp penumbra at the target boundary, and the Bragg peak spots provide a higher linear energy transfer (LET) boost to the target centre.

Methods

Three base of skull chordoma patients were retrospectively planned with three different PBT treatment planning techniques: (1) conventional intensity‐modulated proton therapy (IMPT); (2) high‐energy proton arc therapy (HE‐PAT); and (3) the novel technique combining HE‐PAT and IMPT, referred to as single high‐energy arc with Bragg peak boost (SHARP). The Monaco 6 treatment planning system was used.

Results

SHARP was found to improve the PBT penumbra in the plane perpendicular to the HE‐PAT beams. Minimal penumbra differences were observed in the plane of the HE‐PAT beams. SHARP reduced dose‐averaged LET to surrounding organs at risk.

Conclusion

A novel PBT treatment planning technique was successfully implemented. Initial results indicate the potential for SHARP to improve the penumbra of PBT treatments for base of skull tumours.
Task‐induced changes in brain entropy
Authors: Camargo Aldo , Del Mauro Gianpaolo , Wang Ze
Published: February 2024

Entropy indicates irregularity of a dynamic system, with higher entropy indicating higher irregularity and more transit states. In the human brain, regional brain entropy (BEN) has been increasingly assessed using resting state fMRI (rs‐fMRI), while changes of regional BEN during task‐based fMRI have been scarcely studied. The purpose of this study is to characterize task‐induced regional BEN alterations using the large Human Connectome Project (HCP) data. To control the potential modulation by the block design, BEN of task‐fMRI was calculated from the fMRI images acquired during the task conditions only (task BEN) and then compared to BEN of rs‐fMRI (resting BEN). Moreover, BEN was separately calculated from the control blocks of the task‐fMRI runs (control BEN) and compared to task BEN. Finally, control BEN was compared to resting BEN to test for residual task effects in the control condition. With respect to resting state, task performance unanimously induced BEN reduction in the peripheral cortical area and BEN increase in the centric part of the sensorimotor and perception networks. Control compared to resting BEN showed similar entropy alterations, suggesting large residual task effects. Task compared to control BEN was characterized by reduced entropy in occipital, orbitofrontal, and parietal regions.
Does transcranial direct current stimulation of the primary motor cortex improve implicit motor sequence learning in Parkinson's disease?
Authors: Firouzi Mahyar , Baetens Kris , Swinnen Eva , Baeken Chris , Van Overwalle Frank , Deroost Natacha
Published: February 2024

Implicit motor sequence learning (IMSL) is a cognitive function that is known to be associated with impaired motor function in Parkinson's disease (PD). We previously reported positive effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) on IMSL in 11 individuals with PD with mild cognitive impairments (MCI), with the largest effects occurring during reacquisition. In the present study, we included 35 individuals with PD, with (n = 15) and without MCI (n = 20), and 35 age‐ and sex‐matched controls without PD, with (n = 13) and without MCI (n = 22). We used mixed‐effects models to analyze anodal M1 tDCS effects on acquisition (during tDCS), short‐term (five minutes post‐tDCS) and long‐term reacquisition (one‐week post‐tDCS) of general and sequence‐specific learning skills, as measured by the serial reaction time task. At long‐term reacquisition, anodal tDCS resulted in smaller general learning effects compared to sham, only in the PD group, p = .018, possibly due to floor effects. Anodal tDCS facilitated the acquisition of sequence‐specific learning (M = 54.26 ms) compared to sham (M = 38.98 ms), p = .003, regardless of group (PD/controls). Further analyses revealed that this positive effect was the largest in the PD‐MCI group (anodal: M = 69.07 ms; sham: M = 24.33 ms), p < .001. Although the observed effect did not exceed the stimulation period, this single‐session tDCS study confirms the potential of tDCS to enhance IMSL, with the largest effects observed in patients with lower cognitive status. These findings add to the body of evidence that anodal tDCS can beneficially modulate the abnormal basal ganglia network activity that occurs in PD.
Understanding functional brain reorganization for naturalistic piano playing in novice pianists
Authors: Olszewska Alicja M. , Gaca Maciej , Droździel Dawid , Widlarz Agnieszka , Herman Aleksandra M. , Marchewka Artur
Published: February 2024

Learning to play the piano is a unique complex task, integrating multiple sensory modalities and higher order cognitive functions. Longitudinal neuroimaging studies on adult novice musicians show training‐related functional changes in music perception tasks. The reorganization of brain activity while actually playing an instrument was studied only on a very short time frame of a single fMRI session, and longer interventions have not yet been performed. Thus, our aim was to investigate the dynamic complexity of functional brain reorganization while playing the piano within the first half year of musical training. We scanned 24 novice keyboard learners (female, 18–23 years old) using fMRI while they played increasingly complex musical pieces after 1, 6, 13, and 26 weeks of training. Playing music evoked responses bilaterally in the auditory, inferior frontal, and supplementary motor areas, and the left sensorimotor cortex. The effect of training over time, however, invoked widespread changes encompassing the right sensorimotor cortex, cerebellum, superior parietal cortex, anterior insula and hippocampus, among others. As the training progressed, the activation of these regions decreased while playing music. Post hoc analysis revealed region‐specific time‐courses for independent auditory and motor regions of interest. These results suggest that while the primary sensory, motor, and frontal regions are associated with playing music, the training decreases the involvement of higher order cognitive control and integrative regions, and basal ganglia. Moreover, training might affect distinct brain regions in different ways, providing evidence in favor of the dynamic nature of brain plasticity.
Normal and malaligned talonavicular fusion alters cadaveric foot pressure and kinematics
Authors: Wahl Elizabeth P. , Lin William D. , Whittaker Eric C. , Cook Brian K. , Sangeorzan Bruce J. , Ledoux William R.
Published: February 2024

Talonavicular (TN) fusion is a common treatment for TN arthritis or deformity correction. There is incongruous evidence regarding remaining motion at the talocalcaneal and calcaneocuboid joints after TN fusion. Additionally, the effects of a malaligned TN fusion are not well understood and alignment of the fusion may be important for overall foot integrity. This project assessed the kinematic and kinetic effects of neutral and malaligned TN fusions. Ten cadaveric feet were tested on a gait simulator in four conditions: unfused, fused in neutral, fused in varus, and fused in valgus. The fusions were simulated with external fixation hardware. An eight‐camera motion analysis system and a 10‐segment foot model generated kinematic data, and a pressure mat captured pressure data. Simulated TN fusion was achieved in eight feet. From unfused to fused‐neutral, range of motion (ROM) was not eliminated in the adjacent joints, but the positions of the joints changed significantly throughout stance phase. Furthermore, the ROM increased at the tibiotalar joint. Plantar pressure and center of pressure shifted laterally with neutral fusion. The malalignments marginally affected the ROM but changed joint positions throughout stance phase. Pressure patterns were shifted laterally in varus malalignment and medially in valgus malalignment. The residual motion and the altered kinematics at the joints in the triple joint complex after TN fusion may subsequently increase the incidence of arthritis. Clinical significance: This study quantifies the effects of talonavicular fusion and malalignment on the other joints of the triple joint complex.
Association between 4%‐tetrasodium EDTA and sepsis in neonatal piglets: A retrospective cohort study
Authors: Pauline Mirielle L. , Labonne Evan , Wizzard Pamela R. , Turner Justine M. , Wales Paul W.
Published: February 2024

Background

Central line–associated bloodstream infections are a major concern for children with intestinal failure and in animal research using parenteral nutrition (PN). In neonatal piglets receiving PN, we compared sepsis, line occlusions, line replacements, mortality, and costs with and without the use of a 4%‐tetrasodium ethylenediaminetetraacetic acid (T‐EDTA) locking solution.

Methods

We performed a retrospective review of piglets with a central venous jugular catheter enrolled in 14‐day exclusive PN (TPN) trials or in 7‐day short bowel syndrome (SBS) trials, before and after initiation of T‐EDTA. Lines were locked with a 1‐ml solution for 2 h daily (T‐EDTATPN, n = 17; T‐EDTASBS, n = 48) and compared with our prior standard of care using 1.5‐ml heparin flushes twice daily (CONTPN, n = 34; CONSBS, n = 48). Line patency and signs of sepsis were checked twice daily. Jugular catheters were replaced for occlusions whenever possible. Humane end points were used for sepsis not responding to antibiotic treatment or unresolved catheter occlusions.

Results

Compared with CON, sepsis was reduced using T‐EDTA, significantly for TPN (P = 0.006) and with a trend for SBS piglets (P = 0.059). Line occlusions necessitating line changes were reduced 15% in TPN studies (P = 0.16), and no line occlusions occurred for T‐EDTA SBS piglets.

Conclusion

In our neonatal piglet research, use of T‐EDTA locking solution decreased sepsis and, although not statistically significant, reduced occlusions requiring line replacements. Given the expense of animal research, adding a locking solution must be cost‐effective, and we were able to show that T‐EDTA significantly reduced total research costs and improved animal welfare.
Body composition assessment for sarcopenic obesity and 3‐year mortality in older adults: A comparison study
Authors: Akgul Yavuz Sultan Selim , Akin Sibel , Cengiz Burcu Eren , Kocaslan Derya , Ozer Nurhayat Tugra
Published: February 2024

Background

There is no universally accepted definition of sarcopenic obesity (SO), and its prevalence is ambiguous. This study aimed to investigate the prevalence of SO in older adults based on different definitions and determine which predicts all‐cause mortality.

Methods

This prospective longitudinal follow‐up study included outpatients aged ≥60 years. SO was defined by sarcopenia definition based on the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria plus obesity. Three different methods were used to define obesity. Body mass index (BMI) ≥ 30 kg/m2, waist circumference (WC) ≥ 102 cm for men and ≥88.0 cm for women, and body fat percentage (BF%) ≥ 37.3% for men and ≥51.1% for women. Different definitions of SO and their mortality predictions were compared.

Results

The median age of the 584 patients in the study was 70.0 (interquartile range, 66.0–76.0) years. The prevalence of sarcopenia was 38.5% (47.5% in men and 35.7% in women). The prevalence of SO based on BMI, WC, and BF% was 15.3%, 16.4%, and 10.5%, respectively. The mortality rate was 6.7%. SO based on BMI (odds ratio [OR], 2.73; 95% CI, 1.12–17.9; P = 0.024) and BF% (OR, 1.43; 95% CI, 1.19–3.02; P = 0.007) were significantly associated with 3‐year mortality after adjusting for the confounding variables of age, sex, and number of comorbidities. SO based on WC was not associated with mortality (OR, 0.78; 95% CI, 0.07–1.27; P = 0.104).

Conclusion

The use of BF% and BMI for defining SO is appropriate in outpatient older adults.
Determination of energy requirements after minor burns using indirect calorimetry: A descriptive cohort study
Authors: Rousseau Anne‐Françoise , Fadeur Marjorie , Fauville Jean‐Philippe , Hans Nadine , Martin François , Misset Benoit
Published: February 2024

Background

Minor burns could be associated with moderate hypermetabolism. In this study, the primary outcome was measured energy expenditure (mEE) determined by indirect calorimetry in patients with minor burns. We also compared mEE with predictive values and actual energy intakes.

Methods

Adults with minor burns exclusively treated on an outpatient basis were included. During the week following injury, a dietitian performed indirect calorimetry (Q‐NRG in canopy mode), calculated the estimated energy expenditure (eEE) based on the Harris‐Benedict (HB) and Henry formulas, and evaluated daily energy intakes using a food anamnesis.

Results

Forty‐nine patients (59.2% male; median age: 35 [interquartile range: 29–46.5] years; body mass index [BMI]: 26.2 [22.3–29.6] kg/m2; burn surface area [BSA]: 1.5% [1%–2%]) were included 4 (2–6) days after injury. The mEE was 1863 (1568–2199) kcal or 25 (22.4–28.5) kcal/kg and 1838 (1686–2026) kcal or 26.1 (23.7–27.7) kcal/kg in patients who were respectively fasting for >10 h or not (P = 0.991 or P = 0.805). The total mEE was 104% (95%–116%) and 108% (99%–122%) of the total eEE using the HB and Henry formulas, respectively, with diet‐induced thermogenesis and physical activity level. Hypermetabolism (ie, oxygen consumption at rest ≥3.5 ml/kg/min) was observed in 21/49 (42.9%) patients. Energy intakes corresponded to 71% (60%–86%) of the total mEE.

Conclusion

Performing indirect calorimetry in adults with minor burns revealed that ≥40% of the tested adults presented a hypermetabolism and that their mEE was not covered by their energy intakes.
Outcomes of rectal cancer patients who refuse surgery after incomplete clinical response to neoadjuvant therapy
Authors: Labadie Kevin P. , Olson Kristofor A. , Sun Steven H. , Ituarte Philip H. G. , Hanna Mark , Zerhouni Yasmin , Lai Lily L. , Sentovich Stephen M. , Kaiser Andreas M. , Melstrom Kurt A.
Published: February 2024

Background and Objectives

Total mesorectal excision (TME) remains the standard of care for patients with rectal cancer who have an incomplete response to total neoadjuvant therapy (TNT). A minority of patients will refuse curative intent resection. The aim of this study is to examine the outcomes for these patients.

Methods

A retrospective cohort study of stage 1−3 rectal adenocarcinoma patients who underwent neoadjuvant chemoradiation therapy or TNT at a single institution. Patients either underwent TME, watch‐and‐wait protocol, or if they refused TME, were counseled and watched (RCW). Clinical outcomes and resource utilization were examined in each group.

Results

One hundred seventy‐one patients (Male 59%) were included with a median surveillance of 43 months. Twenty‐nine patients (17%) refused TME and had shortened overall survival (OS). Twelve patients who refused TME converted to a complete clinical response (cCR) on subsequent staging with a prolonged OS. 92% of these patients had a near cCR at initial staging endoscopy. Increased physician visits and testing was utilized in RCW and WW groups.

Conclusion

A significant portion of patients convert to cCR and have prolonged OS. Lengthening the time to declare cCR may be considered in select patients, such as those with a near cCR at initial endoscopic staging.
A Prognostic Model for Cancer‐Specific Survival Among Patients with Nodular Melanoma in Head and Neck
Authors: Fan Fangli , Gou Juxiang , Li Shulian , Ji Qiang
Published: February 2024

Objectives

This study aims to evaluate the correlation between risk factors and treatment methods affecting nodular melanoma (NM) in the head and neck, as well as cancer‐specific survival (CSS), and provide personalized predictive tools for clinical physicians.

Methods

The retrospective study data of 1848 patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. All variables were included in the correlation analysis using the Spearman method. Significant prognostic factors were extracted and integrated through Cox risk regression analysis to construct a nomogram. To assess the performance of the nomogram, Harrell's concordance index (C‐index) and a receiver operating characteristic (ROC) curve analysis were employed.

Results

Spearman's correlation analysis revealed a positive correlation between radiotherapy and lymph node metastasis, whereas chemotherapy showed a stronger association with distant metastasis. However, Cox risk regression analysis demonstrated that Mohs surgery and wide excision with margins exceeding 1 cm yielded substantial therapeutic advantages. Five independent risk prognostic factors (Breslow thickness, ulceration, N classification, M classification, and surgery type) were employed to construct a nomogram. The C‐index for this nomogram was 0.713 for the training set and 0.720 for the validation set. In the training set, the 3‐, 5‐, and 8‐year areas under the curve (AUCs) for CSS were 0.752, 0.723, and 0.720, whereas the validation set's AUCs were 0.754, 0.763, and 0.760, respectively. Calibration curves indicated the nomogram's strong discriminative ability for predicting CSS.

Conclusion

In this study, we identified independent prognostic factors for patients with NM in head and neck and developed a relatively accurate model to predict the survival probability of them, which could contribute to the tumor assessment and clinical decision‐making.

Level of Evidence

3 Laryngoscope, 134:3611–3619, 2024
17β‐estradiol Attenuates the Middle Ear Inflammatory Response to Nontypeable Haemophilus influenzae
Authors: Khampang Pawjai , Samuels Tina L. , Blaine‐Sauer Simon , Lucas Julliette , Yan Ke , Johnston Nikki , Kerschner Joseph E.
Published: February 2024

Objectives

17β‐estradiol (E2) is a steroidal hormone with immunomodulatory functions that play a role in infectious and inflammatory diseases. E2 was recently identified as the leading upstream regulator of differentially expressed genes in a comparative RNA sequencing study of pediatric patients with otitis media (OM) versus OM‐free counterparts and may therefore play a role in the inflammatory response to bacterial otopathogens during pediatric OM. This study examined the effect of E2 on bacterial‐induced inflammatory cytokine expression in an in vitro pediatric OM model.

Methods

An immortalized middle ear (ME) epithelial cell line, ROM‐SV40, was developed from a pediatric recurrent OM patient. The culture was exposed to E2 at physiological levels for 1–48 h prior to 6 h‐stimulation with nontypeable Haemophilus influenzae (NTHi) whole cell lysate. TNFA, IL1B, IL6, and IL8 were assayed by qPCR and ELISA.

Results

E2 pretreatment (24 h) abrogated NTHi induction of IL6; a longer pretreatment (1–10 nM, 48 h) abrogated IL1B induction (p < 0.05). E2 pretreatment (5 nM, 48 h) abrogated NTHi‐induced IL8 secretion (p = 0.017).

Conclusion

E2 pretreatment partially rescued NTHi‐induced cytokine production by ME epithelia. These data support a role for E2 in moderating the excessive inflammatory response to middle ear infection that contributes to OM pathophysiology.

Levels of Evidence

NA Laryngoscope, 134:3815–3819, 2024
The Association Between Obesity and Spontaneous Temporal Bone CSF Leak Outcomes: A Systematic Review and Meta‐Analysis
Authors: Spinos Dimitrios , Geropoulos Georgios , Vavoulis Georgios , Georgountzos Georgios , Papageorgakopoulou Manthia , Karela Nina Rafailia , Varoutis Panagiotis , Evangelou Kyriacos , Cho Wai Sum
Published: February 2024

Objective

We undertook a systematic review of the literature with meta‐analysis to identify the role of obesity (BMI ≥30) in the patient characteristics presenting with spontaneous cerebrospinal fluid (sCSF) leaks of the lateral skull base and the outcomes of their repair.

Data Sources

A Systematic Review of English Articles using MEDLINE, EMBASE, and Cochrane Library.

Review Methods

The research algorithm included the following keywords: “spontaneous CSF leak,” “lateral skull base,” “temporal bone,” “meningocele,” “encephalocele,” and “otorrhea.” We also manually searched the references of included studies, to identify possible studies missed during our literature search.

Results

More than two‐thirds of the patients were female (69.2%) and often were obese (mean BMI 36.5 kg/m2) with a mean age of 57. Most common presenting symptoms were otorrhea and hearing loss. Most authors did not report a routine use of a post‐operative lumbar drain. Most patients had a single skull base defect and encephaloceles prolapsing through, across obese and non‐obese groups. Median length of stay in hospital was 3.2 days, and the majority of patients did not have any recurrence during their follow‐up (89.6%), which was not affected by obesity.

Conclusion

Obesity does not affect length of hospital stay or recurrence rate following surgical repair of lateral skull base sCSF leaks. Surgical repair is a safe and viable approach in the management of obese patients with sCSF leaks in the temporal bone.

Level of Evidence

NA Laryngoscope, 134:2012–2018, 2024
Improving HPV‐Related Oropharyngeal Cancer Knowledge and HPV Vaccination Rates via Virtual Workshops
Authors: Evans Lauran K. , Azar Shaghauyegh S. , Chen Haidee , Saad Miryam , Subhash Sneha , Su‐Velez Brooke M. , St. John Maie A.
Published: February 2024

Objective

To validate the efficacy of a virtual, interdisciplinary workshop in improving HPV knowledge, and vaccination practices among primary care and dental trainees.

Methods

A virtual platform was utilized to hold HPV educational workshops with primary care and dental trainees. Online surveys were distributed before and after the 1‐h interactive workshop, led by otolaryngology residents. Surveys included the workshop's impact on (a) improving knowledge of HPV‐associated oropharyngeal squamous cell carcinoma (OPSCC) and (b) affecting change in HPV vaccination practices. The vaccination rates of trainees were recorded prior to and after workshop attendance.

Results

After the workshop, participants demonstrated significantly improved scores related to knowledge of HPV in the head and neck (p = 0.003) and showed an increased comfort level with counseling on HPV vaccination (p = 0.002). Respondents were also more aware that the HPV vaccine is approved to prevent OPSCC (61% vs. 95%, p < 0.05). Ninety‐seven percent of respondents stated that the workshop changed their HPV vaccination practices, and 95% of those not fully vaccinated stated they would now be more likely to receive the vaccine themselves. There was a significant increase in the average number of HPV vaccines administered at the studied trainee clinic, from 16.83 vaccines/month to 37.6 vaccines/month (percent increase = 123%) in 5 months following the workshop (p = 0.002).

Conclusion

The present interactive virtual workshop demonstrates efficacy in improving HPV‐related knowledge and vaccination practices among trainees. The virtual nature of the course facilitates knowledge transfer and can be used to foster multi‐institutional partnerships regarding medical education and vaccination efforts.

Level of Evidence

4 Laryngoscope, 134:3096–3101, 2024
Choice of Adjuvant Radiotherapy Facility in Major Salivary Gland Cancer
Authors: Patel Aman M. , Haleem Afash , Maxwell Russell , Lukens John N. , Lin Alexander , Brody Robert M. , Brant Jason A. , Carey Ryan M.
Published: February 2024

Objective

Undergoing surgery and adjuvant radiotherapy (aRT) at the same facility has been associated with higher overall survival (OS) in head and neck squamous cell carcinoma. Our study investigates whether undergoing surgery and aRT at the same academic facility is associated with higher OS in major salivary gland cancer (MSGC).

Methods

The 2006–2018 National Cancer Database was queried for patients with MSGC undergoing surgery at an academic facility and then aRT. Multivariable binary logistic and Cox proportional hazards regression models were implemented.

Results

Of 2801 patients satisfying inclusion criteria, 2130 (76.0%) underwent surgery and aRT at the same academic facility. Residence in a less populated area (adjusted odds ratio [aOR] 1.69, 95% confidence interval [CI] 1.16–2.45), treatment without adjuvant chemotherapy (aOR 1.97, 95% CI 1.41–2.76), and aRT duration (aOR 1.02, 95% CI 1.01–1.04) were associated with undergoing surgery and aRT at different facilities on multivariable logistic regression adjusting for patient demographics, clinicopathologic features, and adjuvant therapy (p < 0.01). Five‐year OS was higher in patients undergoing surgery and aRT at the same academic facility (68.8% vs. 61.9%, p < 0.001). Undergoing surgery and aRT at different facilities remained associated with worse OS on multivariable Cox regression (aHR 1.41, 95% CI 1.10–1.81, p = 0.007).

Conclusion

Undergoing surgery and aRT at the same academic facility is associated with higher OS in MSGC. Although undergoing surgery and aRT at the same academic facility is impractical for all patients, academic physicians should consider same‐facility treatment for complex patients who would most benefit from clear multidisciplinary communication.

Level of Evidence

4 Laryngoscope, 134:3620–3632, 2024
Total Laryngectomy for Respiratory Complications From Advanced Duchenne Muscular Dystrophy
Authors: Peleman John , Lin Jared S. , Lin Ho‐Sheng
Published: February 2024

Due to respiratory weakness, late‐stage Duchenne muscular dystrophy (DMD) patients may suffer from chronic aspiration, which is sometimes treated using tracheostomy. However, definitive laryngectomy has not been described in the literature as an aspiration prevention modality in DMD, especially in patients with contraindications to tracheostomy. A case is presented for a patient with advanced stage Duchenne muscular dystrophy suffering from chronic aspiration pneumonia and excessive oral secretions who became ventilator dependent. A tracheostomy was placed, but was noted to have excessive secretions and high cuff pressures, which have been known to be associated with worsened swallow dysfunction as well as tracheoinnominate fistula. The patient therefore was considered for total laryngectomy, which he underwent successfully. Post‐operatively, the patient was noted to have improved subjective quality of life, engaged in an oral diet, and had less secretions surrounding his tracheostoma post‐operatively. Aspiration prevention surgeries are done to improve quality of life by improving oral intake, decreasing the need for frequent suctioning, and can sometimes allow for speech. It is important to consider quality of life for DMD patients as more of these patients are living into their 30s with the aid of mechanical ventilation. Laryngectomy is a surgery that can definitively correct chronic aspiration while allowing for oral intake. Laryngoscope, 134:3677–3678, 2024
A temperature‐controlled, circular maintenance system for studying growth and development of pelagic tunicates (salps)
Authors: Müller Svenja J. , Wessels Wiebke , Driscoll Sara , Pakhomov Evgeny A. , Auerswald Lutz , Michael Katharina , Meyer Bettina
Published: February 2024

Salps have attracted attention as zooplankton organisms that may be able to expand their habitat range and increase their ecological importance in the face of ongoing global warming. Due to their gelatinous nature, unique feeding strategy, and reproductive ecology such changes could have profound impacts on regional marine ecosystems. While their role in the regional carbon cycle is receiving attention, our knowledge of their physiology and life cycle is still limited. This knowledge gap is mainly due to their fragile gelatinous nature, which makes it difficult to capture and maintain intact specimen in the laboratory. We present here a modified kreisel tank system that has been tested onboard a research vessel with the Southern Ocean salp Salpa thompsoni and at a research station with Salpa fusiformis and Thalia democratica from the Mediterranean Sea. Successful maintenance over days to weeks allowed us to obtain relative growth and developmental rates comparable to in situ field samples of S. thompsoni and S. fusiformis, and provided insights into previously unknown features of their life cycle (e.g., testes development). Our results show that traditional methods of estimating growth, such as cohort analysis, may lead to a general overestimation of growth rates and neglect individual strategies (e.g., shrinkage), which can affect the results and conclusions drawn from population dynamic models. By providing a starting point for the successful maintenance of different species, comparable experiments on the physiology of salps is made possible. This will contribute to refining model parameters and improving the reliability of the predictions.
Error‐Free Long‐Lifespan Optical Storage Enhanced by Deep Learning
Authors: Wang Chu‐Han , Ma Jie , Feng Yu‐Du , Xu Xiao‐Yun , Zhang Tian‐Yu , Cheng Ke , Jin Xian‐Min
Published: February 2024

Optical information storage, in virtue of its large capacity, high stability, and long longevity, holds promising prospects in mass storage, while being limited by the trade‐off between readout quality and error rate. The emerging intersection of optical storage and deep learning presents a valuable opportunity to achieve high‐fidelity data storage. Here, a novel paradigm of error‐free long‐lifespan optical storage enhanced is proposed by deep learning, harnessing neural network to extract optical information from birefringence measurements. It is demonstrated that using neural networks outperforms traditional approaches in terms of efficiency and accuracy. Moreover, by adding extra birefringence information as input to the neural network, nearly accuracy is achieved on an established five‐bit dataset. Remarkably, even under extremely severe ambiguity, the paradigm still fulfills error‐free readout and maintains a long lifespan. The experimental storage scheme is significantly conducive to the development of large‐scale error‐free storage, and paves the way for robust optical storage with environmental and temporal tolerance in practical scenarios.
I‐surfaces from surfaces with one exceptional unimodal point
Authors: Rollenske Sönke , Torres Diana
Published: February 2024

We complement recent work of Gallardo, Pearlstein, Schaffler, and Zhang, showing that the stable surfaces with and they construct are indeed the only ones arising from imposing an exceptional unimodal double point.

In addition, we explicitly describe the birational type of the surfaces constructed from singularities of type , , .
Density of smooth functions in Musielak–Orlicz–Sobolev spaces Wk,Φ(Ω)$W^{k,\Phi }(\Omega)$
Authors: Kamińska Anna , Żyluk Mariusz
Published: February 2024

We consider here Musielak–Orlicz–Sobolev (MOS) spaces , where is an open subset of , and is a Musielak–Orlicz function. The main outcomes consist of the results on density of the space of compactly supported smooth functions in . One section is devoted to compare the various conditions on appearing in the literature in the context of maximal operator and density theorems in MOS spaces. The assumptions on we apply here are substantially weaker than in the earlier papers on the topics of approximation by smooth functions. One of the reasons is that in the process of proving density theorems, we do not use the fact that the Hardy–Littlewood maximal operator on Musielak–Orlicz space is bounded, a standard tool employed in density results for different types of Sobolev spaces. We show in particular that under some regularity assumptions on , (A1) and that are not sufficient for the maximal operator to be bounded, the space of is dense in . In the case of variable exponent Sobolev space , we obtain the similar density result under the assumption that , , , , satisfies the log‐Hölder condition and the exponent function is essentially bounded.
The Mullins–Sekerka problem via the method of potentials
Authors: Escher Joachim , Matioc Anca‐Voichita , Matioc Bogdan‐Vasile
Published: February 2024

It is shown that the two‐dimensional Mullins–Sekerka problem is well‐posed in all subcritical Sobolev spaces with . This is the first result, where this issue is established in an unbounded geometry. The novelty of our approach is the use of the potential theory to formulate the model as an evolution problem with nonlinearities expressed by singular integral operators.
Epigenetic modifications in obesity‐associated diseases
Authors: Long Yiqian , Mao Chao , Liu Shuang , Tao Yongguang , Xiao Desheng
Published: February 2024

The global prevalence of obesity has reached epidemic levels, significantly elevating the susceptibility to various cardiometabolic conditions and certain types of cancer. In addition to causing metabolic abnormalities such as insulin resistance (IR), elevated blood glucose and lipids, and ectopic fat deposition, obesity can also damage pancreatic islet cells, endothelial cells, and cardiomyocytes through chronic inflammation, and even promote the development of a microenvironment conducive to cancer initiation. Improper dietary habits and lack of physical exercise are important behavioral factors that increase the risk of obesity, which can affect gene expression through epigenetic modifications. Epigenetic alterations can occur in early stage of obesity, some of which are reversible, while others persist over time and lead to obesity‐related complications. Therefore, the dynamic adjustability of epigenetic modifications can be leveraged to reverse the development of obesity‐associated diseases through behavioral interventions, drugs, and bariatric surgery. This review provides a comprehensive summary of the impact of epigenetic regulation on the initiation and development of obesity‐associated cancers, type 2 diabetes, and cardiovascular diseases, establishing a theoretical basis for prevention, diagnosis, and treatment of these conditions.
Autoimmune Movement Disorders Complicating Treatment with Immune Checkpoint Inhibitors
Authors: Dinoto Alessandro , Trentinaglia Milena , Carta Sara , Mantovani Elisa , Ferrari Sergio , Tamburin Stefano , Tinazzi Michele , Mariotto Sara
Published: February 2024

Background

Immune checkpoint inhibitors (ICI) may trigger autoimmune neurological conditions, including movement disorders (MD).

Objectives

The aim of this study was to characterize MDs occurring as immune‐related adverse events (irAEs) of ICIs.

Methods

A systematic literature review of case reports/series of MDs as irAEs of ICIs was performed.

Results

Of 5682 eligible papers, 26 articles with 28 patients were included. MDs occur as a rare complication of cancer immunotherapy with heterogeneous clinical presentations and in most cases in association with other irAEs. Inflammatory basal ganglia T2/fluid attenuated inversion recovery abnormalities are rarely observed, but brain imaging is frequently unrevealing. Cerebrospinal fluid findings are frequently suggestive of inflammation. Half of cases are associated with a wide range of autoantibodies. Steroids and ICI withdrawal usually lead to improvement, even though some patients experienced relapses or a severe clinical course.

Conclusion

MDs are a rare complication of ICIs that should be promptly recognized to offer patients a correct diagnosis and treatment.
Tax incentives, common institutional ownership, and corporate ESG performance
Authors: Huang Chengjie , Zhou Hang , Norhayati Wan Ahmad , Saad Ram Al Jaffri , Zhang Xinrui
Published: February 2024

Against the backdrop of sustainable development, enterprises, the general public, and regulatory bodies are exhibiting an escalating level of concern regarding the performance in environmental stewardship, social responsibility, and corporate governance collectively referred to as ESG (Environmental, Social Responsibility, and Corporate Governance). This research, from the vantage point of external fiscal policy, investigates the examination of the impact of tax incentives on corporate ESG performance. Drawing upon panel data spanning from 2010 to 2021 at the level of China's A‐share listed companies and grounded in the context of accelerated depreciation policy for fixed assets, this study commitment to both identify and empirically test the presence of a significant positive correlation between tax incentives and corporate ESG performance. Our analysis of the financial mechanism and the Research and Development (R&D) mechanism reveals that tax incentives are instrumental in alleviating the financing constraints faced by corporations, thereby augmenting their financial performance. Furthermore, they serve to intensify R&D efforts, thereby fostering the generation of green innovations. In conclusion, our findings underscore that tax incentive policies significantly enhance the ESG performance of enterprises with common institutional shareholdings, an effect attributed to the presence of governance and synergy effects.
Interleaved Propofol‐Ketamine Maintains DBS Physiology and Hemodynamic Stability: A Double‐Blind Randomized Controlled Trial
Authors: Kornilov Evgeniya , Baker Erdman Halen , Kahana Eilat , Fireman Shlomo , Zarchi Omer , Israelashvili Michal , Reiner Johnathan , Glik Amir , Weiss Penina , Paz Rony , Bergman Hagai , Tamir Idit
Published: February 2024

Background

The gold standard anesthesia for deep brain stimulation (DBS) surgery is the “awake” approach, using local anesthesia alone. Although it offers high‐quality microelectrode recordings and therapeutic‐window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy.

Objectives

The aim is to investigate a novel anesthesia regimen of ketamine‐induced conscious sedation for the physiological testing phase of DBS surgery.

Methods

Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events.

Results

Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part‐III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively.

Conclusions

Ketamine‐induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post‐operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
A homozygous stop codon in HORMAD2 in a patient with recurrent digynic triploid miscarriage
Authors: Liang Manqi , Suresh Beena , Bareke Eric , Choufani Sanaa , Jagadeesh Sujatha , Weksberg Rosanna , Majewski Jacek , Slim Rima
Published: February 2024

Background

Recurrent miscarriage (RM) affects 1% to 5% of couples trying to conceive. Despite extensive clinical and laboratory testing, half of the RM cases remain unexplained. We report the genetic analysis of a couple with eight miscarriages and the search for their potential genetic etiology.

Methods

Short tandem repeat (STR) markers, single nucleotide polymorphic (SNP) microarray, and human DNA methylation microarray were used to analyze the genotypes of two miscarriages. Exomes sequencing was performed on DNA from the two partners and identified variants were validated by Sanger sequencing.

Results

STR marker genotyping demonstrated that the two available miscarriages are triploid digynic and resulted from the failure of Meiosis II. SNP microarray analysis revealed an additional Meiosis I abnormality that is the segregation of the two maternal homologous chromosomes in one triploid miscarriage. Whole‐exome sequencing on DNA from the two partners identified candidate variants only in the female partner in two genes with roles in female reproduction, a missense in EIF4ENIF1 (OMIM 607445) and a stop gain in HORMAD2 (OMIM 618842). EIF4ENIF1 is a eukaryotic translation initiation factor 4E nuclear import factor required for the oocyte germinal vesicle breakdown, and HORMAD2 is part of the synaptonemal complex that was hypothesized to act as a checkpoint mechanism to eliminate oocytes with asynapsis during meiotic prophase I in mice.

Conclusion

While both genes may contribute to the phenotype, the Meiosis I abnormalities in the conceptions favor the causal role of HORMAD2 in the etiology of RM in this couple. This report illustrates the importance of comprehensively analyzing the products of conception to guide the search for the genetic causation of RM.