bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpreting the Evolutionary Echoes of a Protein Complex Essential for Inner-Ear Mechanosensation
Authors: Nisler Collin R , Narui Yoshie , Scheib Emily , Choudhary Deepanshu , Bowman Jacob D , Mandayam Bharathi Harsha , Lynch Vincent J , Sotomayor Marcos
Published: March 2023

The sensory epithelium of the inner ear, found in all extant lineages of vertebrates, has been subjected to over 500 million years of evolution, resulting in the complex inner ear of modern vertebrates. Inner-ear adaptations are as diverse as the species in which they are found, and such unique anatomical variations have been well studied. However, the evolutionary details of the molecular machinery that is required for hearing are less well known. Two molecules that are essential for hearing in vertebrates are cadherin-23 and protocadherin-15, proteins whose interaction with one another acts as the focal point of force transmission when converting sound waves into electrical signals that the brain can interpret. This "tip-link" interaction exists in every lineage of vertebrates, but little is known about the structure or mechanical properties of these proteins in most non-mammalian lineages. Here, we use various techniques to characterize the evolution of this protein interaction. Results show how evolutionary sequence changes in this complex affect its biophysical properties both in simulations and experiments, with variations in interaction strength and dynamics among extant vertebrate lineages. Evolutionary simulations also characterize how the biophysical properties of the complex in turn constrain its evolution and provide a possible explanation for the increase in deafness-causing mutants observed in cadherin-23 relative to protocadherin-15. Together, these results suggest a general picture of tip-link evolution in which selection acted to modify the tip-link interface, although subsequent neutral evolution combined with varying degrees of purifying selection drove additional diversification in modern tetrapods.
DNA i-motif formation at neutral pH is driven by kinetic partitioning
Authors: Školáková Petra , Gajarský Martin , Palacký Jan , Šubert Denis , Renčiuk Daniel , Trantírek Lukáš , Mergny Jean-Louis , Vorlíčková Michaela
Published: March 2023

Cytosine-rich DNA regions can form four-stranded structures based on hemi-protonated C.C+ pairs, called i-motifs (iMs). Using CD, UV absorption, NMR spectroscopy, and DSC calorimetry, we show that model (CnT3)3Cn (Cn) sequences adopt iM under neutral or slightly alkaline conditions for n > 3. However, the iMs are formed with long-lasting kinetics under these conditions and melt with significant hysteresis. Sequences with n > 6 melt in two or more separate steps, indicating the presence of different iM species, the proportion of which is dependent on temperature and incubation time. At ambient temperature, kinetically favored iMs of low stability are formed, most likely consisting of short C.C+ blocks. These species act as kinetic traps and prevent the assembly of thermodynamically favored, fully C.C+ paired iMs. A higher temperature is necessary to unfold the kinetic forms and enable their substitution by a slowly developing thermodynamic structure. This complicated kinetic partitioning process considerably slows down iM folding, making it much slower than the timeframes of biological reactions and, therefore, unlikely to have any biological relevance. Our data suggest kinetically driven iM species as more likely to be biologically relevant than thermodynamically most stable iM forms.
Discovery of natural non-circular permutations in non-coding RNAs
Authors: Eckert Iris , Friedrich Richard , Weinberg Christina E , Weinberg Zasha
Published: March 2023

Research in the last two decades has increasingly demonstrated that RNA has capabilities comparable to those of proteins, for example the ability to form intricate 3D structures necessary for catalysis. Numerous protein domains are known in varied within-domain rearrangements, called permutations, that change the N- to C-terminal order of important amino acids inside the domain, but maintain their 3D locations. In RNAs, by contrast, only simple circular permutations are known, in which 5′ and 3′ portions of the molecule are merely swapped. Here, we computationally find and experimentally validate naturally occurring RNAs exhibiting non-circular permutations of previously established hammerhead ribozyme RNAs. In addition to the rearranged RNAs, a bioinformatics-based search uncovered many other new conserved RNA structures that likely play different biological roles. Our results further demonstrate the structural sophistication of RNA, indicate a need for more nuance in the analysis of pseudoknots, and could be exploited in RNA-based biotechnology applications.
Tissue-specific regulation of gene expression via unproductive splicing
Authors: Mironov Alexei , Petrova Marina , Margasyuk Sergey , Vlasenok Maria , Mironov Andrey A , Skvortsov Dmitry , Pervouchine Dmitri D
Published: March 2023

Eukaryotic gene expression is regulated post-transcriptionally by a mechanism called unproductive splicing, in which mRNA is triggered to degrade by the nonsense-mediated decay (NMD) pathway as a result of regulated alternative splicing (AS). Only a few dozen unproductive splicing events (USEs) are currently documented, and many more remain to be identified. Here, we analyzed RNA-seq experiments from the Genotype-Tissue Expression (GTEx) Consortium to identify USEs, in which an increase in the NMD isoform splicing rate is accompanied by tissue-specific down-regulation of the host gene. To characterize RNA-binding proteins (RBPs) that regulate USEs, we superimposed these results with RBP footprinting data and experiments on the response of the transcriptome to the perturbation of expression of a large panel of RBPs. Concordant tissue-specific changes between the expression of RBP and USE splicing rate revealed a high-confidence regulatory network including 27 tissue-specific USEs with strong evidence of RBP binding. Among them, we found previously unknown PTBP1-controlled events in the DCLK2 and IQGAP1 genes, for which we confirmed the regulatory effect using small interfering RNA (siRNA) knockdown experiments in the A549 cell line. In sum, we present a transcriptomic pipeline that allows the identification of tissue-specific USEs, potentially many more than were reported here using stringent filters.
Insights into translocation mechanism and ribosome evolution from cryo-EM structures of translocation intermediates of Giardia intestinalis
Authors: Majumdar Soneya , Emmerich Andrew , Krakovka Sascha , Mandava Chandra Sekhar , Svärd Staffan G , Sanyal Suparna
Published: March 2023

Giardia intestinalis is a protozoan parasite that causes diarrhea in humans. Using single-particle cryo-electron microscopy, we have determined high-resolution structures of six naturally populated translocation intermediates, from ribosomes isolated directly from actively growing Giardia cells. The highly compact and uniquely GC-rich Giardia ribosomes possess eukaryotic rRNAs and ribosomal proteins, but retain some bacterial features. The translocation intermediates, with naturally bound tRNAs and eukaryotic elongation factor 2 (eEF2), display characteristic ribosomal intersubunit rotation and small subunit’s head swiveling—universal for translocation. In addition, we observe the eukaryote-specific ‘subunit rolling’ dynamics, albeit with limited features. Finally, the eEF2·GDP state features a uniquely positioned ‘leaving phosphate (Pi)’ that proposes hitherto unknown molecular events of Pi and eEF2 release from the ribosome at the final stage of translocation. In summary, our study elucidates the mechanism of translocation in the protists and illustrates evolution of the translation machinery from bacteria to eukaryotes from both the structural and mechanistic perspectives.
Almonertinib Combined with Anlotinib and Temozolomide in a Patient with Recurrent Glioblastoma with EGFR L858R Mutation
Authors: Hou Zhiwei , Wu Huaguo , Luo Ningning , Li Shuo , Zhang Xiang , Dong Shuai , Zhu Dongyuan , Zhang Hui , Tao Rongjie
Published: March 2023

Glioblastoma (GBM) is the most common primary brain tumor, and patients with GBM have a universally poor prognosis. Genomic profiling has detected epidermal growth factor receptor (EGFR) gene alterations in more than half of GBMs. Major genetic events include amplification and mutation of EGFR. Interestingly, we identified an EGFR p.L858R mutation in a patient with recurrent GBM for the first time. Based on the genetic testing results, almonertinib combined with anlotinib and temozolomide was administered and obtained 12 months of progression-free survival after the diagnosis of recurrence as the fourth-line treatment. This is the first report that an EGFR p.L858R mutation was identified in a patient with recurrent GBM. Furthermore, this case report represents the first study applying the third-generation TKI inhibitor almonertinib in the treatment of recurrent GBM. The results of this study indicate that EGFR might be a new marker for the treatment of GBM with almonertinib.
Analysis of companion cell and phloem metabolism using a transcriptome-guided model of Arabidopsis metabolism
Authors: Hunt Hilary , Brueggen Nico , Galle Alexander , Vanderauwera Sandy , Frohberg Claus , Fernie Alisdair R , Sonnewald Uwe , Sweetlove Lee J
Published: March 2023

Companion cells and sieve elements play an essential role in vascular plants, and yet the details of the metabolism that underpins their function remain largely unknown. Here, we construct a tissue-scale flux balance analysis (FBA) model to describe the metabolism of phloem loading in a mature Arabidopsis (Arabidopsis thaliana) leaf. We explore the potential metabolic interactions between mesophyll cells, companion cells, and sieve elements based on the current understanding of the physiology of phloem tissue and through the use of cell type–specific transcriptome data as a weighting in our model. We find that companion cell chloroplasts likely play a very different role to mesophyll chloroplasts. Our model suggests that, rather than carbon capture, the most crucial function of companion cell chloroplasts is to provide photosynthetically generated ATP to the cytosol. Additionally, our model predicts that the metabolites imported into the companion cell are not necessarily the same metabolites that are exported in phloem sap; phloem loading is more efficient if certain amino acids are synthesized in the phloem tissue. Surprisingly, in our model predictions, the proton-pumping pyrophosphatase (H+-PPiase) is a more efficient contributor to the energization of the companion cell plasma membrane than the H+-ATPase.
THE NATIONAL RESEARCH COUNCIL OF CANADA MANGANESE BATH SYSTEM
Authors: Archambault J P
Published: March 2023

The manganese salt bath is considered a primary standard for determining the absolute emission rate of radionuclide neutron sources. The National Research Council of Canada has recently revived its manganese salt bath and a full description of the system is given here. The physical characteristics of the bath, as well as the methods for determining the efficiency of the bath system and the induced activity in the bath, are described. An in-depth analysis of the fraction of neutrons captured in the manganese and the correction factor for neutron losses is also provided. Finally, the results of emission rate measurements of four different sources, complete with an uncertainty budget, are given. The emission rates of three americium-beryllium neutron sources and one californium-252 neutron source were found to agree with the known values, within a standard uncertainty of 1.7%.
Altered Associations Between Motivated Performance and Frontostriatal Functional Connectivity During Reward Anticipation in Schizophrenia
Authors: Smucny Jason , Hanks Timothy D , Lesh Tyler A , O’Reilly Randall C , Carter Cameron S
Published: March 2023

Background and hypothesis

The neuronal mechanisms that underlie deficits in effort cost computation in schizophrenia (SZ) are poorly understood. Given the role of frontostriatal circuits in valence-oriented motivation, we hypothesized that these circuits are either dysfunctional in SZ or do not appropriately predict behavior in SZ when task conditions are difficult and good performance is rewarded.

Study design

A total of 52 people with recent onset SZ-spectrum disorders and 48 healthy controls (HCs) performed a 3T fMRI task with 2 valence conditions (rewarded vs neutral) and 2 difficulty conditions. Frontostriatal connectivity was extracted during the cue (anticipatory) phase. Individual behavior was fit using a drift-diffusion model, allowing the performance parameter, drift rate (DR), to vary between task conditions. Three models were examined: A group × condition model of DR, a group × condition model of connectivity, and a regression model of connectivity predicting DR depending on group and condition.

Study results

DRs showed the expected positive correlation with accuracy and a negative association with reaction time. The SZ group showed a deficit in DR but did not differ in overall connectivity or show a valence-specific deficit in connectivity. Significant group × valence × difficulty interactions, however, were observed on the relationship between right dorsolateral prefrontal (DLPFC)-striatal connectivity and DR (DLPFC-Caudate: F = 10.92, PFDR = .004; DLPFC-Putamen: F = 5.14, PFDR = .048) driven by more positive relationships between DR and connectivity during cues for the difficult-rewarded condition in HCs compared to SZ.

Conclusions

These findings suggest that frontostriatal connectivity is less predictive of performance in SZ when task difficulty is increased and a reward incentive is applied.
Chest radiograph findings in children with COVID-19—A retrospective analysis from a tertiary care paediatric hospital in South India
Authors: Vendhan Kanimozhi , Kathirrajan Mithra , Kathirvelu Gopinathan , S Balasubramanian
Published: March 2023

Objective

The primary aim of this study is to document the chest X-ray findings in children with COVID-19 pneumonia. The secondary aim is to correlate chest X-ray findings to patient outcome.

Methods

We performed a retrospective analysis of children (0–18 years) with SARS-CoV-2 admitted to our hospital from June 2020 to December 2021. The chest radiographs were assessed for: peribronchial cuffing, ground-glass opacities (GGOs), consolidation, pulmonary nodules and pleural effusion. The severity of the pulmonary findings was graded using a modification of the Brixia score.

Results

There were a total of 90 patients with SARS-CoV-2 infection; the mean age was 5.8 years (age range 7 days to 17 years). Abnormalities were seen on the CXR in 74 (82%) of the 90 patients. Bilateral peribronchial cuffing was seen in 68% (61/90), consolidation in 11% (10/90), bilateral central GGOs in 2% (2/90) and unilateral pleural effusion in 1% (1/90). Overall the average CXR score in our cohort of patients was 6. The average CXR score in patients with oxygen requirement was 10. The duration of hospital stay was significantly longer in those patients with CXR score >9.

Conclusion

The CXR score has the potential to serve as tool to identify children at high risk and may aid planning of clinical management in such patients.
Inclusion of Spanish-Speaking Families in NICU Symptom Research Using a Community Advisory Board
Authors: Garcia Dana , Fortney Christine A. , Gerhardt Cynthia A. , Baughcum Amy E. , Slaughter Jonathan L. , Rodriguez Erin M.
Published: March 2023

Background:

Admission rates of Hispanic/Latinx families to the neonatal intensive care unit (NICU) are rising, yet knowledge regarding their experiences is limited. Non-English-speaking families are often excluded from research because study measures are not available in their language. The inclusion of these families in NICU research is crucial to understand the impact of cultural and language barriers in infant and family care, and the translation of study measures into Spanish could better ensure that these families' perspectives are included. However, previous research has utilized the standard translation–backtranslation method with which problems have been noted.

Purpose:

This article describes the planning, preparation, and action phases that were completed with the use of a community advisory board (CAB) to prepare and transcreate research study materials from English to Spanish for pilot testing.

Methods:

Community members of interest were invited to form the CAB, and 2 meetings were held to review study materials in the English and Spanish versions. Prior to the second meeting, a professional translation company translated study materials from English to Spanish.

Results:

Feedback from the CAB ensured consistent content and reading levels, and culturally appropriate language usage. The CAB also provided suggestions to the research protocol and advised sensitive methods of recruitment and measure administration.

Implications for Practice and Research:

More accurate and culturally appropriate transcreation of study measures can reduce barriers to research participation and facilitate better communication with non-English-speaking families in health equity research to better inform evidence-based interventions and clinical practices across diverse groups.
Rheumatologic immune checkpoint inhibitor-related adverse events
Authors: Defoe Melissa , Bermas Bonnie L.
Published: March 2023

Purpose of review

Immune check point inhibitors (ICIs) are a unique class of cancer treatments that harness the body's innate antitumor response. Although these medications have transformed oncology care, they also lead to generalized immune activation that can result in toxicities across a spectrum of organ systems called immune-related adverse events. This article reviews the most common rheumatologic immune-related adverse events and their management.

Recent findings

Inflammatory arthritis, polymyalgia rheumatic, sicca symptoms, systemic sclerosis, myositis, and vasculitis have all been reported as ICI adverse events. Treatment includes nonsteroidal anti-inflammatory drugs, glucocorticoids, traditional DMARDs, and biologics.

Rheumatologists have an important role in the management of patients with rheumatologic immune-related adverse events. Working with our oncology colleagues, we can help manage rheumatologic immune-related adverse events while optimally preserving ICI's antitumor effects.
Evaluating the association between race and complications following pediatric upper extremity surgery
Authors: Gupta Puneet , Palosaari Andrew , Quan Theodore , Ifarraguerri Anna M. , Tabaie Sean
Published: March 2023

Race can influence perioperative care and outcomes in adult and pediatric orthopedic surgery. However, no prior study has evaluated any associations between race and complications following upper extremity surgery in pediatric patients. Thus, the purpose of this study was to evaluate whether there are any differences in risks for complications, readmission, or mortality following upper extremity surgery between African American and Caucasian pediatric patients. Pediatric patients who had a primary upper extremity procedure from 2012 to 2019 were identified in the National Surgical Quality Improvement Program-Pediatric database. Patients were categorized into two cohorts: patients who were Caucasian and patients who were African American. Differences in demographics, comorbidities, and postoperative complications were assessed and compared between the two-patient population using bivariate and multivariable regression analyses. Of the 25 848 pediatric patients who underwent upper extremity surgeries, 21 693 (83.9%) were Caucasian, and 4155 (16.1%) were African American. Compared to Caucasian patients, African American patients were more likely to have a higher American Society of Anesthesiologists classification (P < 0.001), as well as pulmonary comorbidities (P < 0.001) and hematologic disorders (P = 0.004). Following adjustment on multivariable regression analysis to control for baseline characteristics, there were no differences in any postoperative complications between Caucasian and African American patients. In conclusion, African American pediatric patients are not at an increased risk for postoperative complications compared to Caucasian patients following upper extremity surgery. Race should not be used independently when evaluating patient risk for postoperative complications. Level of Evidence: III.
Characterization of patients with a diagnosis of breast cancer and melanoma: genetic susceptibility or increased surveillance?
Authors: Jia Karen Y. , Menes Tehillah S. , Bernstein-Molho Rinat , Nissan Aviram , Zippel Dov
Published: March 2023

Background

Breast cancer diagnosis had been linked to an increased risk of melanoma in several reports. The aim of the current study was to assess the role of genetics, increased surveillance, and radiation treatment in patients with a dual diagnosis of breast cancer and melanoma (DBM).

Materials and methods

All patients treated at Sheba Medical Center between 2007 and 2021 with DBM were included in the cohort. Data on family history, genetic tests, characteristics, and treatment of both cancers were collected. The proportion of patients with a pathogenic variant (PV) in BRCA1 and BRCA2 genes was compared to a control group of patients with breast cancer. The proportion of patients presenting with in-situ disease was compared to the national registry data.

Results

The cohort included 222 DBM patients of whom 114 had documentation of genetic testing. Twenty patients tested positive for PVs of which 13 (11%) were in BRCA genes. This was comparable to the proportion in patients with a diagnosis of breast cancer (736; 19%). The proportion of melanoma diagnosed at stage 0 was comparable to the national proportion (N = 40; 30% vs. 28%, respectively). In comparison to the national registry, a larger proportion of breast cancers were ductal carcinoma in situ or lobular carcinoma in situ [10% in the registry vs. 19% (22) in the cohort; P < 0.003].

Conclusions

In patients with DBM we did not find an increased proportion of PVs in BRCA genes. Our findings suggest that the increased standardized incidence ratio of the dual diagnosis may be partially explained by increased surveillance and detection of earlier-stage cancers.
The Impact of Psychedelic Drugs on Anxiety and Depression in Advanced Cancer or other Life-threatening Disease
Authors: Sicignano Dakota , Snow-Caroti Kimberly , Hernandez Adrian V. , White C. Michael
Published: March 2023

Objectives:

Life-threatening cancer or other diseases can induce anxiety and depressive symptoms. We performed a systematic review with meta-analyses of randomized controlled trials assessing patients with cancer or other life-threatening diseases using validated anxiety and depression scales.

Methods:

PubMed was searched up to November 15, 2022 and citations were applied to prespecified inclusion criteria. Disease rating scales for anxiety or depression included the State-Trait Anxiety Inventory (STAI) (STAI Trait [STAI-T], STAI-State [STAI-S]), Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS) (HADS-Anxiety [HADS-A]; HADS-Depression [HADS-D]), Profile of Mood States (POMS), and the Hamilton Rating Scale for Depression (HAM-D or GRID-HAM-D-17). Safety outcomes included assessments of blood pressure and heart rate.

Results:

Five trials, predominantly in cancer patients, had data assessing anxiety and depressive symptoms. These trials found promising results for psychedelics versus placebo in several anxiety and depression scales but increases in blood pressure and heart rate also occurred. There were some concerns of risk of bias because it is difficult to truly randomize a psychedelic trial and there was a high percentage of patients in the trials who had used psychedelics in the past. There was high heterogeneity for all analyses that we could not explain.

Conclusions:

Although the results are promising, future trials are needed to assess the optimal psychedelic, dose, number of sessions required, and how psychedelic naïve patients would respond both psychologically and hemodynamically before this therapy can be considered for widescale clinical use.
Is it Worthy Enough to Revascularize Chronically Occluded Coronaries?
Authors: Sahu Ankit Kumar , Kazmi Danish Hasan , Kaushik Atul
Published: March 2023

Chronic total occlusions (CTOs) represent the “final frontier” of coronary interventions with the lowest procedural success rates and the most common reason for incomplete revascularization and referral to coronary artery bypass graft surgery (CABG). CTO lesions are not an infrequent finding during coronary angiography. They are often responsible for enhancing the complexity of the coronary disease burden thereby affecting the final interventional decision in the process. Notwithstanding the modest technical success of CTO-PCI, most of the earlier observational data demonstrated a clear survival benefit free of major cardiovascular events (MACE) in patients undergoing successful CTO revascularization. However, data from recent randomized trials fail to uphold the same survival advantage albeit, showing some trend toward improvement in left ventricular function, quality of life indicators and freedom from fatal ventricular arrythmia. Various guidance statements propose a well-defined role for CTO intervention in specific situations provided criterions for patient selection, appreciable inducible ischemia, myocardial viability and cost-risk-benefit analysis are met.
Differences of sexual development: genetic counseling considerations in the prenatal setting
Authors: Chen Kelly , Dunleavy Brooke M. , Talreja Karina L. , Jones Renee
Published: March 2023

Purpose of review

With the rapid adoption of noninvasive prenatal screening (NIPS), predictive fetal sex information is available early in pregnancy. This information can conflict with the results of other prenatal tests such as fetal ultrasound or diagnostic testing and raise the possibility of a fetal difference of sexual development (DSD). In this review, we describe recent studies examining the counseling and outcomes of prenatally suspected DSD.

Recent findings

Discordance in prenatal genetic testing results can cause confusion and anxiety in families as expectations of testing are not often discussed in detail prior to testing. There are no established guidelines for the counseling or management of such situations.

We present case vignettes to highlight relevant counseling points and considerations to aid in the development of guidelines and best practices in the management of DSD in the prenatal setting.
Undiagnosed Patent Foramen Ovale and Thrombophilic Gene Mutations Resulting in Pulmonary Embolism with Cryptogenic Stroke after Cosmetic Breast Surgery
Authors: Zaussinger Maximilian , Speiser Sophie , Wenny Raphael , Schmidt Manfred
Published: March 2023

Undiagnosed disorders or gene mutations can lead to life-threatening events even in cosmetic surgery. Herein, the authors present a case of a young and supposedly healthy 36-year-old woman who survived an episode of bilateral pulmonary embolism and cryptogenic stroke after cosmetic breast augmentation-mastopexy. Two days after cosmetic surgery, the patient presented at the emergency stroke unit after she collapsed at home, following frequent generalized seizures. After she was transferred to the intensive care unit, it was revealed that the patient had an undiagnosed patent foramen ovale and several thrombophilic gene mutations. During the stay, two episodes of active bleeding and beginning nipple-areola complex hypoperfusion led to bilateral implant removal. As a final result, the patient lost her breast implants and experienced persistent hypoesthesia of the entire left hemi body. However, this case might highlight deficits in current venous thromboembolism risk assessment and prophylaxis due to the missing considerations of undiagnosed disorders or gene mutations. Further, recommendations on dealing with implants or aesthetic outcome in crucial episodes should be introduced.
Pulmonary Embolism after Liposuction Totally by Tumescent Local Anesthesia in a Patient with Large Uterine Fibroids
Authors: Norman Nicholas C. , Klein Paytra A. , Choi Noah J. , Smith David G. , Klein Jeffrey A.
Published: March 2023

A fatal pulmonary embolism occurred in a 43-year-old black woman after tumescent liposuction totally by local anesthesia. An autopsy revealed large uterine fibroids, peri-uterine vascular thrombi, and a large saddle pulmonary embolism. Large uterine fibroids are a risk factor for postsurgical venous thromboembolism. Fatal outcomes after tumescent liposuction totally by local anesthesia are exceedingly rare.
The Effect of Socioeconomic Disparity on Improvement in QuickDASH at 3 Months after Carpal Tunnel Release
Authors: Zhang Dafang , Blazar Philip , Earp Brandon E.
Published: March 2023

Background:

The primary objective of this study was to determine the association between socioeconomic disparity and improvement in QuickDASH score 3 months after carpal tunnel release (CTR). The secondary objectives of this study were to determine the association between socioeconomic disparity and baseline preoperative QuickDASH score and 3 months postoperative QuickDASH score after CTR.

Methods:

A single-institutional, prospective, longitudinal study was performed of 85 patients who underwent isolated, unilateral CTR for idiopathic carpal tunnel syndrome. Sixty-three patients (74%) who completed patient-reported outcome measures at 3 months after surgery comprised our study cohort. Socioeconomic disparity was assessed using the zip code level Distressed Communities Index (DCI) and the neighborhood level Area Deprivation Index. The outcome variables were the improvement in the QuickDASH score, 3 months postoperative QuickDASH score, and the preoperative QuickDASH score. Associations between continuous variables were assessed using simple linear regression.

Results:

The mean DCI of the study cohort was in the 23rd national percentile, and the mean Area Deprivation Index was in the 15th national percentile. The mean preoperative QuickDASH of the study cohort was 49.3. The mean 3 months postoperative QuickDASH of the study cohort was 29.8. The mean improvement in QuickDASH at 3 months after surgery was 19.5, which was statistically significant and clinically meaningful. Area Deprivation Index and DCI were not associated with improvement in QuickDASH score or 3 months postoperative QuickDASH score. Higher DCI was associated with poorer baseline preoperative QuickDASH score.

Conclusion:

Patients of various socioeconomic backgrounds can expect similar short-term improvements in symptoms and function after CTR.
Demystifying Targeted Muscle Reinnervation: A Systematic Review of Nerve Transfers for the Lower Extremity
Authors: Henderson Joshua T. , Koenig Zachary A. , Climov Mihail , Gelman Jack
Published: March 2023

Background:

Targeted muscle reinnervation (TMR) outcome studies reveal the benefit amputees experience and the potential functional improvement by optimizing neurocutaneous signaling for myoelectric prosthesis control. However, there are still many settings where these techniques are not offered to patients requiring lower extremity amputations or neuroma reconstruction. With growing consistency in the literature, it is helpful to systematize the nerve transfers described for lower extremity TMR and to simplify its integration into reconstructive care.

Methods:

A systematic literature review was performed and contained the following inclusion criteria: original cases of primary or secondary lower extremity amputation defects or nerve-related pain that underwent TMR with clearly described target muscles for each nerve transfer. Studies were excluded if the cases had been previously described or contained incomplete data. The primary outcomes were nerves transferred and muscles targeted. Target muscle options were presented in tables specific to anatomic region, and cross-sectional schematics were created for intraoperative assistance.

Results:

Seventeen studies presenting original cases with clearly described nerve transfers and target muscles in the lower extremity were included in the review. Target muscle selection for all nerve transfers at the transfemoral and transtibial levels were presented in separate tables.

Conclusions:

Reports of early experience at multiple institutions identify trends in the selection of certain target muscles for nerve transfers in transfemoral and transtibial TMR. Familiarity with these common target muscles and nerve transfers can simplify intraoperative decision-making and enhance integration of lower extremity TMR in amputation care and in the treatment of nerve-related pain.
Unilateral endophthalmitis after immediate sequential bilateral cataract surgery in a cognitively impaired patient: diagnosis and treatment
Authors: Martinez Jaime D. , Levine Harry , Flynn Harry W. , Schwartz Stephen G.
Published: March 2023

Introduction:

Immediate sequential bilateral cataract surgery (ISBCS) is a reasonable approach for cataract surgery in patients needing general anesthesia, such as those with cognitive impairment. To our knowledge, this is the first reported case of unilateral acute-onset postoperative endophthalmitis in a patient with cognitive impairment after ISBCS, with emphasis on diagnostic and treatment challenges.

Patient and Clinical Findings:

A 64-year-old woman with a history of cognitive impairment, seizure disorder, and no prior ocular surgery presented with dense visually significant cataracts and visual acuity of fix and follows in both eyes.

Diagnosis, Intervention, and Outcomes:

Patient underwent ISBCS under general anesthesia and without intracameral antibiotics or corneal sutures. The patient returned with unilateral acute-onset endophthalmitis 2 weeks postoperatively. Because of the patient's limited ability to comply with treatment, and lack of emergency general anesthesia needed for vitreous cultures, intravitreal vancomycin injection (1 mg/0.1 mL) was empirically given, with clinical resolution of the infection and visual acuity of fix and follows.

Conclusions:

Acute-onset postoperative endophthalmitis in the setting of cognitive impairment is challenging because emergency general anesthesia may not be available, and the patient can tolerate only limited interventions. In this patient, empiric intravitreal vancomycin injection without cultures led to a satisfactory clinical outcome.
A comparative study of the hemodynamic and clinical effects of using or not tourniquet in total knee arthroplasty
Authors: Hung Shih-Hsin , Chiu Fang-Yao , Cheng Ming-Fai
Published: March 2023

Background:

Pneumatic tourniquet is widely used in lower limb surgery to provide a bloodless operating field. Previous studies on total knee arthroplasty (TKA) in which tourniquets have been applied during surgery have reported some vascular and soft-tissue complications. Nevertheless, it is still not well known exactly how use of tourniquets contributes to hemodynamics of the lower limb and its clinical relevance following TKA. In this prospective study, we wished to determine whether tourniquet affects the hemodynamics and postoperative healing of the lower limb in the first few weeks and its clinical relevancies following TKA.

Methods:

We prospectively collected consecutive 110 patients with advanced osteoarthritis of the knee. All the subjects were randomly assigned to one of two TKA procedures: TKA with (Group T) or without (Group O) tourniquets. The hemodynamics of each operated leg was assessed by Doppler, first before the operation, then postoperatively on days 2, 6, 14, and 28. The operative and postoperative managements were done the same as those described in the papers done by the author. Parameters during the operative and postoperative course, including, demography, pre- or postoperative knee score, tourniquet time, operation time, estimated blood loss, perioperative blood transfusion, hospital course, and complications will all be recorded and compared in detail. All patients were measured for all response variables, which included demographic variables, results of Doppler, and important surgical outcomes. Fisher’s exact test was used to compare differences between the two groups for each discrete variable, and a Mann-Whitney Rank Sum Test was used to analyze each continuous variable. The p value was set for each test at 0.05 before analysis took place. In accordance with the repeated measures, the venous hemodynamic parameters were checked. If any significant differences appeared in the overall test, values were then compared in pairs using two sample t-tests for all statistical tests. The level of significance was set at p < 0.05.

Results:

In our 110 patients (55 with tourniquet, 55 without), all checked clinical parameter were without significant difference except postoperative quadriceps muscle recovery. This implied tourniquet use influenced postoperative rehabilitation program. Blood loss amount were similar in both groups. There was only one DVT found.

Conclusion:

Tourniquet use in TKA must be managed very carefully. Not only because of immediate complication resulted from tourniquet but also influence on post-operational functional recovery, especially in quadriceps muscle function. According to this study, TKA without tourniquet use preserves better quadriceps muscle function to provide faster recovery and less transfusion need. It avoids complications from tourniquets as well.
Custom Silicone Distal Cup Designed and Fabricated Using 3D Optical Scanning and Additive Manufacturing to Improve Socket Fit of an Individual with Tranfemoral Amputation with Irregular Distal Residual Limb Morphology
Authors: Putra Ketut B. , Bolger Darren , Posh Ryan , Wensman Jeffrey , Shih Albert
Published: March 2023

Introduction

The study presents the design and manufacturing of a custom silicone distal cup, with a high spatial resolution, to fit inside the prosthetic liner for the treatment of irregular morphology at the distal residual limb of a patient with lower-limb amputation. This distal cup for the inside of the prosthetic liner has intricate interior features matching the shape of the distal residual limb to prevent localized high-pressure regions.

Methods

High-resolution 3D optical scanning, computer-aided design (CAD), and material extrusion (MEX) process for additive manufacturing of molds are three key techniques for designing and manufacturing this custom distal cup. A three-part mold for molding the distal cup with matching features was designed by CAD and fabricated by MEX. The subject evaluated the distal cup by walking using the distal cup before wearing the prosthetic liner in the lower-limb prosthesis.

Results

A custom silicone distal cup was fabricated using a 3D-printed mold and evaluated using a Prosthetic User’s Survey. Based on the survey, the insert has an acceptable comfort, suspension requirement, and ease of use.

Conclusions

The scan by high spatial resolution Space Spider optical scanner could capture detailed features of the distal residual limb. The resulting distal cup had the protrusion that functioned to separate the invaginations. The subject was satisfied with the distal cup based on the Prosthetic User’s Survey.

Clinical Relevance

The approach to fabricate the custom silicone distal cup using a high-resolution 3D optical scanner and a 3D-printed mold can be applied to fabricate the distal cup with intricate features for a patient with irregular morphology at the distal residual limbs.
Regional differences in bone mineral density biomechanically induce a higher risk of adjacent vertebral fracture after percutaneous vertebroplasty: a case-comparative study
Authors: Li Jingchi , Xie Yimin , Sun Shenglu , Xue Congyang , Xu Wenqiang , Xu Chen , Xi Zhipeng
Published: March 2023

Background:

Adjacent vertebral fracture (AVF) is a frequently observed complication after percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compressive fracture. Biomechanical deterioration initially induces a higher risk of AVF. Studies demonstrated that the aggravation of regional differences in the elastic modulus of different components might deteriorate the local biomechanical environment and increase the risk of structural failure. Considering the existence of intravertebral regional differences in bone mineral density (BMD) (i.e. elastic modulus), it was hypothesized in the present study that higher intravertebral BMD differences may induce a higher risk of AVF biomechanically.

Materials and Methods:

The radiographic and demographic data of osteoporotic vertebral compressive fracture patients treated using PVP were reviewed in the present study. The patients were divided into two groups: those with AVF and those without AVF. The Hounsfield unit (HU) values of transverse planes from the superior to the inferior bony endplate were measured, and the differences between the highest and lowest HU values of these planes were considered the regional differences of the HU value. The data from patients with and without AVF were compared, and the independent risk factors were identified through regression analysis. PVP with different grades of regional differences in the elastic modulus of the adjacent vertebral body was simulated using a previously constructed and validated lumbar finite element model, and the biomechanical indicators related to AVF were computed and recorded in surgical models.

Results:

Clinical data on 103 patients were collected in this study (with an average follow-up period of 24.1 months). The radiographic review revealed that AVF patients present a significantly higher regional difference in the HU value and that the increase in the regional difference of the HU value was an independent risk factor for AVF. In addition, numerical mechanical simulations recorded a stress concentration tendency (the higher maximum equivalent stress value) in the adjacent vertebral cancellous bone, with a stepwise aggravation of the adjacent cancellous bony regional stiffness differences.

Conclusions:

The aggravation of regional BMD differences induces a higher risk of AVF after PVP surgery through a deterioration of the local biomechanical environment. The maximum differences in the HU value of the adjacent cancellous bone should, therefore, be measured routinely to better predict the risk of AVF. Patients with noticeable regional BMD differences should be considered at high risk for AVF, and greater attention must be paid to these patients to reduce the risk of AVF.

Evidence grade:

Level III b.
Cochlear implant in tinnitus management
Authors: Bahmad Fayez , Carasek Natália , Lamounier Pauliana
Published: March 2023

Purpose of review

To evaluate whether cochlear implantation can mitigate tinnitus perception and its discomfort among patients with severe-to-profound hearing loss, in order to provide an answer on a possible treatment for a health condition with high prevalence and impact on quality of life.

Recent findings

Tinnitus can develop after peripheral hearing loss and is associated with altered auditory processing. It does not only involve auditory structures but also aberrant neural activity and interaction with other regions of the Central Nervous System associated with emotion, attention, anguish, memory and motor activity.

Recent studies investigated the changes in tinnitus perception among patients who underwent cochlear implantation and demonstrated a postoperative decrease. Hence, patients with severe-to-profound sensorineural hearing loss and tinnitus are likely to benefit from cochlear implantation.
Modern treatment of sinonasal undifferentiated carcinoma
Authors: Neo Wei Li , Hanna Ehab Y. , Kiong Kimberley L.
Published: March 2023

Purpose of review

Sinonasal undifferentiated carcinomas are rare aggressive tumours with traditionally poor outcomes. Although multimodality treatment has been recommended by most centres, the ideal treatment sequence or regimen has not been established.

Recent findings

Recent evidence suggests that induction chemotherapy may be used for chemoselection and cytoreduction prior to definitive chemoradiotherapy. Where there is a favourable response, concurrent chemoradiotherapy is favoured, with an improved overall survival and improved rates of organ preservation.

Induction chemotherapy may be a useful guide for selection of patients for chemoradiotherapy or surgery and has shown encouraging results. Further research is required to establish the ideal induction chemotherapy regimen for this rare group of tumours.
The role of transoral surgery in the diagnosis of the carcinoma of unknown origin of the head and neck
Authors: Mehanna Hisham
Published: March 2023

Purpose of review

The aim of this article is to update readers on the most recent evidence on the role of trans oral surgery (TOS) in the diagnosis of carcinoma of the unknown primary of the head and neck.

Recent findings

Tongue base mucosectomy has an important role in identifying the primary in patients who have had negative imaging, PET CT scans and ipsilateral tonsillectomy. In patients with bilateral nodal disease, tongue base mucosectomy should precede tonsillectomy. There are several unanswered questions that remain regarding sequencing of operations and use of intraoperative frozen section.

An evidence-based approach to diagnosis is important to ensure the highest detection rates, and least morbidity, in patients with head and neck carcinoma of the unknown primary.
Addressing patients’ concerns in speech and language therapy consultations following the diagnosis and treatment of head and neck cancer
Authors: Zuydam Annette C. , Rogers Simon N. , Roe Justin W.G.
Published: March 2023

Purpose of review

Head and neck cancer (HNC) and its treatment impacts profoundly on patients’ functional abilities, emotional well being and social interactions. Communication and swallowing are fundamental to everyday life, and the Speech and Language Therapist (SLT) has a critical role for both patients and their carers. In clinical practice, patient-reported outcome measures (PROMs) are a key part of the armamentarium of the SLT. The purpose of the review is to summarize how these measures can be beneficial in the context of time pressured SLT outpatient consultations.

Recent findings

Unmet needs in HNC are common and impact negatively on quality of life. There is an ever-increasing number of articles in this area, and it can be a challenge to identify, distil and summarize those specific to SLT.

In this review, we discuss the scope of holistic evaluation, strengths and limitations of PROMs, the Patient Concerns Inventory-Head and Neck, barriers to the use of outcome measures, the carers perspective and surveillance. SLT are uniquely placed members of the multidisciplinary team and provide expert advice and intervention. The inclusion of PROMs in routine consultations provides a model of follow up, which helps address patients and carers complex and unmet needs, ultimately promoting better outcomes.