bluuebunny/crossref_metadata_2025 huggingface dataset:
The ubiquitin-specific protease USP36 SUMOylates EXOSC10 and promotes the nucleolar RNA exosome function in rRNA processing
Authors: Chen Yingxiao , Li Yanping , Dai Roselyn S , Savage Jonathan C , Shinde Ujwal , Klimek John , David Larry L , Young Emma A , Hafner Markus , Sears Rosalie C , Sun Xiao-Xin , Dai Mu-Shui
Published: March 2023

The RNA exosome is an essential 3′ to 5′ exoribonuclease complex that mediates degradation, processing and quality control of virtually all eukaryotic RNAs. The nucleolar RNA exosome, consisting of a nine-subunit core and a distributive 3′ to 5′ exonuclease EXOSC10, plays a critical role in processing and degrading nucleolar RNAs, including pre-rRNA. However, how the RNA exosome is regulated in the nucleolus is poorly understood. Here, we report that the nucleolar ubiquitin-specific protease USP36 is a novel regulator of the nucleolar RNA exosome. USP36 binds to the RNA exosome through direct interaction with EXOSC10 in the nucleolus. Interestingly, USP36 does not significantly regulate the levels of EXOSC10 and other tested exosome subunits. Instead, it mediates EXOSC10 SUMOylation at lysine (K) 583. Mutating K583 impaired the binding of EXOSC10 to pre-rRNAs, and the K583R mutant failed to rescue the defects in rRNA processing and cell growth inhibition caused by knockdown of endogenous EXOSC10. Furthermore, EXOSC10 SUMOylation is markedly reduced in cells in response to perturbation of ribosomal biogenesis. Together, these results suggest that USP36 acts as a SUMO ligase to promote EXOSC10 SUMOylation critical for the RNA exosome function in ribosome biogenesis.
SCRAPT: an iterative algorithm for clustering large 16S rRNA gene data sets
Authors: Luan Tu , Muralidharan Harihara Subrahmaniam , Alshehri Marwan , Mittra Ipsa , Pop Mihai
Published: March 2023

16S rRNA gene sequence clustering is an important tool in characterizing the diversity of microbial communities. As 16S rRNA gene data sets are growing in size, existing sequence clustering algorithms increasingly become an analytical bottleneck. Part of this bottleneck is due to the substantial computational cost expended on small clusters and singleton sequences. We propose an iterative sampling-based 16S rRNA gene sequence clustering approach that targets the largest clusters in the data set, allowing users to stop the clustering process when sufficient clusters are available for the specific analysis being targeted. We describe a probabilistic analysis of the iterative clustering process that supports the intuition that the clustering process identifies the larger clusters in the data set first. Using real data sets of 16S rRNA gene sequences, we show that the iterative algorithm, coupled with an adaptive sampling process and a mode-shifting strategy for identifying cluster representatives, substantially speeds up the clustering process while being effective at capturing the large clusters in the data set. The experiments also show that SCRAPT (Sample, Cluster, Recruit, AdaPt and iTerate) is able to produce operational taxonomic units that are less fragmented than popular tools: UCLUST, CD-HIT and DNACLUST. The algorithm is implemented in the open-source package SCRAPT. The source code used to generate the results presented in this paper is available at https://github.com/hsmurali/SCRAPT.
G-quadruplex-based CRISPR photoswitch for spatiotemporal control of genomic modulation
Authors: Deng Huaping , Xu Han , Wang Yiru , Jia Ruizhen , Ma Xiaoqian , Feng Yushuo , Chen Hongmin
Published: March 2023

CRISPR (clustered regularly interspaced short palindromic repeats) technology holds tremendous promise for gene regulation and editing. However, precise control of CRISPR editing is essential to overcome its uncontrollable reaction process and excessive activity that leads to off-target editing. To overcome this problem, we engineered a photoswitch on G-quadruplex gRNA (GqRNA) for precisely controlled gene editing and expression by embedding dicationic azobenzene derivatives (AZD++). Our results demonstrated that rational design of the G-quadruplex onto crRNA conferred higher stability and sequence recognition specificity than unmodified single guide (sgRNA). Light-induced isomerization of AZD++ quickly transformed the on state of GqRNA, which facilitated rapid activation of ribonucleoprotein activity for genome editing of on-target sites in cells with excellent editing efficiency. In turn, AZD++–GqRNA promptly refolded to an off state to inhibit genomic cleavage, and limited the generation of off-target effects and by-products. Therefore, the proposed strategy of a photo-reversible modality presents a new opportunity for CRISPR-Cas9 modulation to improve its safety and applicability.
Housing: the key infrastructure to achieving health and wellbeing in urban environments
Authors: O’Sullivan K C , Olin C V , Pierse N , Howden-Chapman P
Published: March 2023

Informed by research undertaken by our teams with community partners over the past 25 years primarily in Aotearoa New Zealand, we examine housing as an infrastructure required to support health and wellbeing. The home environment is where people spend most of their time, so we propose that housing is the key infrastructure to enhance and maintain health and wellbeing outcomes in urban environments. Other foundational infrastructures—including energy, food, waste, transport, information communications technology, water and sanitation, green, community, education and health care—equally support and rely on housing infrastructure to shape the places in which an increasing diversity of people and their communities live. We describe how housing infrastructure in neoliberal, market-based housing systems has contributed to inequities in access to high-quality housing and connected health-supporting infrastructures. We share two illustrative vignettes of housing retrofits and urban development from Aotearoa and Sweden to show that when approached in a comprehensive, proactive and inclusive way that prioritizes people and the environment, these infrastructures may yet have untapped potential for improving health and wellbeing.
Citrus ACC synthase CiACS4 regulates plant height by inhibiting gibberellin biosynthesis
Authors: Chu Le Le , Yan Zhen , Sheng Xing Xing , Liu Hai Qiang , Wang Qing Ye , Zeng Ren Fang , Hu Chun Gen , Zhang Jin Zhi
Published: March 2023

Dwarfism is an agronomic trait that has substantial effects on crop yield, lodging resistance, planting density, and a high harvest index. Ethylene plays an important role in plant growth and development, including the determination of plant height. However, the mechanism by which ethylene regulates plant height, especially in woody plants, remains unclear. In this study, a 1-aminocyclopropane-1-carboxylic acid synthase (ACC) gene (ACS), which is involved in ethylene biosynthesis, was isolated from lemon (Citrus limon L. Burm) and named CiACS4. Overexpression of CiACS4 resulted in a dwarf phenotype in Nicotiana tabacum and lemon and increased ethylene release and decreased gibberellin (GA) content in transgenic plants. Inhibition of CiACS4 expression in transgenic citrus significantly increased plant height compared with the controls. Yeast two-hybrid assays revealed that CiACS4 interacted with an ethylene response factor (ERF), CiERF3. Further experiments revealed that the CiACS4–CiERF3 complex can bind to the promoters of 2 citrus GA20-oxidase genes, CiGA20ox1 and CiGA20ox2, and suppress their expression. In addition, another ERF transcription factor, CiERF023, identified using yeast one-hybrid assays, promoted CiACS4 expression by binding to its promoter. Overexpression of CiERF023 in N. tabacum caused a dwarfing phenotype. CiACS4, CiERF3, and CiERF023 expression was inhibited and induced by GA3 and ACC treatments, respectively. These results suggest that the CiACS4–CiERF3 complex may be involved in the regulation of plant height by regulating CiGA20ox1 and CiGA20ox2 expression levels in citrus.
Potential diagnostic biomarkers for lead-induced hepatotoxicity and the role of synthetic chelators and bioactive compounds
Authors: Lakka Netranandini , Pai Bhagyashree , Mani Monica Shirley , Dsouza Herman Sunil
Published: March 2023

Lead (Pb2+) poisoning is a public health concern of global dimensions. Although several public health guidelines and workplace safety policies are existing and enforced, lead toxicity cases are drastically increasing. Lead exposure leads to numerous harmful consequences and causes adverse effects on different body organs and systems, mainly via the generation of reactive oxygen species, leading to augmented oxidative stress, competing with metal ions, and binding with the sulfhydryl groups. In several instances, lead poisoning cases remain undiagnosed and untreated or receive only symptomatic treatment. Estimation of blood lead levels reflects only a recent exposure, however, which does not reveal the total body burden. This review summarizes the effects of lead with special reference to hepatotoxicity and some of the potential diagnostic biomarkers. Furthermore, it also focuses on synthetic chelators used in the treatment of lead poisoning and the advantage of using bioactive compounds with an emphasis on the ameliorative effect of garlic.
Tocilizumab in giant cell arteritis: an update for the clinician
Authors: Ford Julia A. , Gewurz Danya , Gewurz-Singer Ora
Published: March 2023

Purpose of review

The recent approval of tocilizumab (TCZ) for the treatment of giant cell arteritis (GCA) has changed the landscape for management of this disease. Herein, we review recent literature addressing practical questions for the clinician regarding the use of TCZ in GCA. We evaluate efficacy of TCZ across different disease phenotypes, optimal dosing and formulation, treatment-related toxicity, recommendations for monitoring disease, and duration of therapy.

Recent findings

Post-hoc analyses of a large clinical trial and real-world data suggest efficacy of TCZ across various disease phenotypes in GCA, and support use of weekly subcutaneous dosing over every-other-week dosing. More data are needed to guide duration of TCZ therapy, optimal disease activity monitoring in patients treated with TCZ, and to speak to efficacy in GCA with large vessel involvement.

TCZ has added valuably to the treatment arsenal in GCA, though more data are needed to guide optimal use of the drug.
Reliability of assessing proximal femur geometry with Rutz classification schema in patients with cerebral palsy
Authors: Kasprzyk Maciej , Koch Aleksander , Karbowski Lukasz M. , Jóźwiak Marek , Narayanan Unni G.
Published: March 2023

Our investigation aimed to assess the reliability of the femoral head shape classification system devised by Rutz et al. and observe its application in patients with cerebral palsy (CP) at different skeletal maturity levels. Four independent observers assessed anteroposterior radiographs of the hips of 60 patients with hip dysplasia associated with non-ambulatory CP (Gross Motor Function Classification System levels IV and V) and recorded the femoral head shape radiological grading system as described by Rutz et al. Radiographs were obtained from 20 patients in each of three age groups: under 8 years, between 8 and 12 years and above 12 years old, respectively. Inter-observer reliability was assessed by comparing the measurements of four different observers. To determine the intra-observer reliability, radiographs were reassessed after a 4-week interval. Accuracy was checked by comparing these measurements with the assessment of expert consensus. Validity was checked indirectly by observing the relationship between the Rutz grade and the migration percentage. The Rutz classification system’s evaluation of femoral head shape showed moderate to substantial intra- and inter-observer reliability (mean κ = 0.64 for intraobserver and mean κ = 0.5 for interobserver). Specialist assessors had slightly higher intra-observer reliability than trainee assessors. The grade of femoral head shape was significantly associated with increasing migration percentage. Rutz’s classification was shown to be reliable. Once the clinical utility of this classification can be established, it has the potential for broad application for prognostication and surgical decision-making and as an essential radiographic variable in studies involving the outcomes of hip displacement in CP. Level of evidence: III.
Contemporary management of epilepsy in pregnancy
Authors: Darmawan Kelly F. , Panelli Danielle M.
Published: March 2023

Purpose of review

The number of reproductive aged people with epilepsy in the United States is increasing, making epilepsy during pregnancy more prevalent. Simultaneously, more people are using newer generations of antiseizure medications before, during and after pregnancy. Here, we review current evidence on contemporary management and outcomes of pregnancies among people with epilepsy.

Recent findings

This review evaluates recent literature to summarize current practices in preconception counselling, contraception, antiseizure medications before, during and after pregnancy, and peri-partum and postpartum risks in people with epilepsy.

With the introduction of newer generation antiseizure medications being used during pregnancy, current literature shows that there may be decreased risk in adverse foetal and maternal outcomes. In the peri-partum and postpartum period, recent literature shows that people with epilepsy have an increased risk of severe maternal morbidity and hospital readmission. Given this, as well as considerations for dosing of antiseizure medications, close surveillance of people with epilepsy during pregnancy is warranted.
Management of blood pressure in pregnancy: new perspectives from the CHAP trial
Authors: Holliman Kerry D. , Lowe Virginia , Nonni Gabriella
Published: March 2023

Purpose of review

Chronic hypertension affects up to 10% of pregnancies in the United States and the incidence of hypertensive diseases of pregnancy has more than doubled in the past decade, affecting minority women at disproportionate rates. Recent data show potential benefit by lowering the threshold of blood pressure treatment for pregnant women to >140/90 mmHg.

Recent findings

In April 2022, the results of the Chronic Hypertension and Pregnancy (CHAP) trial was published and demonstrated that lower thresholds (>140/90 vs. >160/110 mmHg) for the initiation of antihypertensive therapy during pregnancy resulted in better pregnancy outcomes without negative impacts to foetal growth. In addition, professional societies, such as the American College of Obstetrics and Gynecology (ACOG) and the Society of Maternal Fetal Medicine (SMFM), have released statements supporting the initiation of antihypertensive therapy at elevations above 140/90 mmHg for pregnant women with chronic hypertension based upon these recent reports.

Treatment of hypertension in pregnant women is controversial, but recent data are emerging that treatment at lower blood pressure thresholds may be associated with improved perinatal outcomes without an increased risk of poor foetal growth. Although these recommendations may be applied to women with chronic hypertension, more research is needed to determine how these guidelines should be applied to other hypertensive diseases of pregnancy.
The pregnancy at risk for delivery at the threshold of viability
Authors: Boddy Mark G. , Davis Alexis S. , Perlman Nicola
Published: March 2023

Purpose of review

To examine updated recommendations for obstetrical interventions that may improve neonatal outcomes in extremely preterm births.

Recent findings

Several recent studies of antenatal steroids at the threshold of viability have demonstrated benefits in both survival and survival without major morbidity. This has led to revised recommendations from the American College of Obstetricians and Gynecologist regarding the timing of antenatal steroids in these extremely preterm fetuses.

These recent developments have important implications for clinical care in patients at risk for extremely preterm birth based on a model of best practices and shared decision-making.
Successful Management of a High-output Lymphorrhea via Lymphaticovenous Anastomosis after Cannulation for Cardiopulmonary Bypass
Authors: Sloan Chad S. , Hon Heidi H. , Figy Sean C.
Published: March 2023

Lymphatic leaks are a rare phenomenon, but can be a troublesome and persistent problem, especially in an already debilitated patient. Historically, management of lymphorrhea has involved non- and minimally-invasive techniques of elevation, compression, aspiration, or drain placement, among others. Ligation and sclerotherapy are additional utilized techniques, directly targeting the lymphatic vessel. Microsurgical management of lymphatic leaks via lymphaticolymphatic and lymphaticovenous anastomosis has gained popularity amongst surgeons as an alternative solution to the problem. We present a patient who developed a high-output lymphocutaneous fistula after a femoral cannulation procedure for cardiopulmonary bypass for an orthotopic heart transplantation. After multiple unsuccessful attempts at traditional management options, the patient had a successful resolution of the high-output lymphorrhea via a lymphaticovenous anastomosis utilizing end-to-end coaptation with an interpositional vein graft. This case uniquely describes a lymphaticovenous anastomosis and bypass of a lymph node in the setting of significant lymphorrhea (>1.0 L per day) and associated lymphocutaneous fistula, that was effectively managed in the acute postoperative setting. Management of lymphorrhea by microsurgical techniques and lymphatic vessel manipulation in the postoperative period provides surgeons with an enhanced option for direct operative management of lymphatic vessels and their associated sequelae.
PATHOLOGIC STUDY OF UNTREATED INTRARETINAL GLIOSIS SURGICALLY EXCISED VIA PARS PLANA VITRECTOMY
Authors: Wu Mengai , Ren Xinyu , Chen Yan , Chen Lifeng , Lian Hengli , Li Haidong , Li Qiuming , Zheng Bin
Published: March 2023

Purpose:

To evaluate the pathologic process of intraretinal glioses by investigating mass tissues resected from untreated eyes with intraretinal glioses.

Methods:

Five patients with intraretinal gliosis without previous conservative treatment were included. All patients underwent pars plana vitrectomy. The mass tissues were excised and processed for the pathologic study.

Results:

During surgery, it was observed that the intraretinal gliosis mainly affected the neuroretina and the retinal pigment epithelium was not affected. Pathologic examination revealed that all intraretinal glioses consisted of different proportions of hyaline vessels and hyperplastic spindle-shaped glial cells. In one case, the intraretinal gliosis was mainly composed of hyaline vascular components. In another case, the intraretinal gliosis showed a predominance of glial cells. The intraretinal glioses in the other three cases had vascular and glial components. The proliferated vessels showed different amounts of collagen deposits against different backgrounds. Vascularized epiretinal membrane was found in some intraretinal glioses.

Conclusion:

Intraretinal glioses affected the inner retinal layer. Hyaline vessels were the most characteristic pathologic changes; the proportion of proliferative glial cells varied in different intraretinal glioses. The natural course of intraretinal gliosis may involve the proliferation of abnormal vessels in the early stage, which then gradually become scarred and are replaced by glial cells.
BULBOSITIES AND INTERVORTEX VENOUS ANASTOMOSIS IN VENOUS OVERLOAD CHOROIDOPATHY MASQUERADING AS POLYPOIDAL CHOROIDAL VASCULOPATHY
Authors: Ngo Wei Kiong , Keshet Yariv , Spaide Richard F.
Published: March 2023

Purpose:

To describe a patient with venous overload choroidopathy in whom venous bulbosities masqueraded as polyps and intervortex venous anastomosis mimicked a branching vascular network, giving the appearance of polypoidal choroidal vasculopathy.

Methods:

The patient had complete ophthalmic examination including indocyanine green angiography and optical coherence tomography. Venous bulbosities were defined on indocyanine green angiography as focal dilations in which the diameter of the dilation is two times that of the host vessel.

Results:

A 75-year-old woman presented with combined subretinal and subretinal pigment epithelium hemorrhages in the right eye. During indocyanine green angiography, focal nodular hyperfluorescent lesions connected to a network of vessels were observed, which looked like polyps and branching vascular network in polypoidal choroidal vasculopathy. In both eyes, the midphase angiogram had multifocal choroidal vascular hyperpermeability. There was late-phase placoid staining nasal to the nerve in the right eye. During enhanced depth imaging–optical coherence tomography evaluation, there were no retinal pigment epithelium elevations that would be expected with polyps or branching vascular network in the right eye. A double-layer sign was seen corresponding to the placoid area of staining. Diagnosis of venous overload choroidopathy and choroidal neovascularization membrane was made. She was treated with intravitreal antivascular endothelial growth factor injections for the choroidal neovascularization membrane.

Conclusion:

Indocyanine green angiography findings in venous overload choroidopathy may mimic polypoidal choroidal vasculopathy, but differentiation is essential because it has implications for treatment. Similar findings may have been misinterpreted in the past and may have previously contributed to conflicting clinical and histopathologic descriptions of polypoidal choroidal vasculopathy.
Relative efficacy of prophylactic strategies for postthyroidectomy hypocalcemia: a systematic review and network meta-analysis
Authors: Ren Shuling , Zhu Yiyuan , Dong Yanbo , Cui Jianxin , Wang Yunyun , Li Guo , Zhang Aobo , Liu Liangfa
Published: March 2023

Background:

Routine prophylaxis for at-risk patients may reduce the occurrence of postoperative hypocalcemia but is not widely adopted due to a lack of evidence on the efficacy of available prophylactic strategies. In this study, we compared the relative efficacy of prophylactic strategies for postthyroidectomy hypocalcemia with a systematic review and network meta-analysis.

Methods:

PubMed, Embase, and Cochrane Library were searched, covering the period from 1980 to May 2022, for randomized controlled trials (RCTs) comparing calcium, vitamin D3, activated vitamin D3, teriparatide, steroids, and magnesium with placebo or each other in patients receiving total or completion thyroidectomy. Involved RCTs reporting symptomatic or biochemical hypocalcemia. The primary outcome was symptomatic hypocalcemia, defined as circumoral tingling, and Chvostek and Trousseau signs. The secondary outcome was biochemical hypocalcemia. Risk of bias was assessed using the Cochrane risk of bias assessment tool for randomized trials. Pooled estimates were calculated using a random-effects inverse-variance weighting model. The network meta-analysis was performed under the frequentist framework. This meta-analysis was registered on the PROSPERO (International prospective register of systematic reviews) (CRD42022299982).

Results:

Twenty-seven RCTs comprising 3382 patients are included. Prophylactic strategies of teriparatide, oral calcium plus vitamin D3, and oral calcium plus activated vitamin D3 are superior to placebo in reducing symptomatic hypocalcemia. Teriparatide emerged as the most effective strategy for symptomatic hypocalcemia [relative risk (RR): 0.18; 95% CI: 0.03–0.98], followed by oral calcium plus activated vitamin D3 (RR: 0.42; 95% CI: 0.25–0.73) and oral calcium plus vitamin D3 (RR: 0.43; 95% CI: 0.26–0.71). Evidence on monotherapy with either oral calcium or vitamin D3 in reducing symptomatic hypocalcemia is insufficient. Intravenous calcium and oral calcium are effective in reducing biochemical hypocalcemia.

Conclusions:

This network meta-analysis provides information on the relative efficacy of current prophylactic strategies for postthyroidectomy hypocalcemia. Teriparatide performed better than other interventions and would seem appropriate for deployment among high-risk populations.
Biomechanics of surgical knot security: a systematic review
Authors: Wong Yoke-Rung , McGrouther Duncan A.
Published: March 2023

Background:

This review aims to identify publications on quantitative biomechanical testing of surgical knot security and the physical factors that determine knot security and failure.

Materials and Methods:

An electronic literature search was performed in accordance with PRISMA guidelines in January 2022 utilizing the PubMed and Google Scholar databases to look for objective biomechanical studies on knot security in surgery using the primary terms ‘knot security’ and ‘biomechanical testing’.

Results:

Thirty-six articles were included. Twenty-four configurations of surface, laparoscopic, and arthroscopic knots were studied. Biomechanical tensile testing was used to evaluate knot security in vitro. Load to failure (N) and elongation at knot failure (mm) were quantified by static and cyclic testing to evaluate the knot holding capacity and failure mechanism of slippage or rupture.

Conclusion:

This review reassures that the knot configuration, suture materials, suture sizes, and number of throws are key factors in determining the knot’s security. Knot configuration has to be simple for laparoscopic and arthroscopic knots due to the confined space of the operating site. With the advent of stronger suture materials for high-tension surgical reconstructive procedures, there is an unmet need to understand the physical behavior of the knot and the factors that determine its resistance to slippage or rupture.

Level of Evidence: Level IV.
Philosophy and Philology: Two Approaches of Commentating the Shen Nong Ben Cao Jing (Shen Nong’s Classic of the Materia Medica) in the Ming and Qing Dynasties
Authors: CHANG Che-chia
Published: March 2023

This paper tests the hypothesis that the commentary trend of the Shen Nong Ben Cao Jing (Shen Nong’s Classic of the Materia Medica) arises alongside the fashionable philology of the time, or the aversion against the Jin-Yuan medical philosophy. After surveying 12 major commentaries, it is concluded that the situation is more complicated than a simple assertion. The seemingly opposite philosophy and philology approaches have been used eclectically to innovate the understanding of ancient traditional Chinese medicine texts.
Food and Medicine: Qualities and Efficacies in Chinese Ethnic Medicines
Authors: Lili LAI , Farquhar Judith
Published: March 2023

Drawing on our research in China’s southern mountains about ethnic medicines, and intrigued by the proverbial Chinese view that Yao Shi Tong Yuan (food and medicine have the same source), this article traces the eventfulness and powers at play in healing and eating when they are seen as closely related forms of life. Ancient and modern traditional Chinese medicine understandings of flavor are here shown to be a common basis for the healing and harming powers of both food and medicine. The term Wu Wei, or five flavors is explored as both experiences of eating and cooking, and some patterns of qi movement that animate and invigorate the body. Following Vivienne Lo’s term “potent flavors,” practices of harmonizing (He, Tiao He) flavors in Chinese medicine, as in cooking, express a world of natural powers and expert embodiment that goes far beyond mere taste.
Hereditary head and neck paraganglioma: from basics to practical consequences
Authors: Trache Mihnea Cristian , Böttcher Arne , Betz Christian Stephan
Published: March 2023

Purpose of review

This review summarizes practical recommendations for screening, work-up, and management of hereditary head and neck paragangliomas based on the growing molecular and empirical understanding of this disease.

Recent findings

The proportion of hereditary cases among head and neck paragangliomas is significant (∼33 to 50%), and specific genetic alterations may increase the risk of malignancy. Genotyping should be performed for each case, and patients carrying a pathological mutation should be regularly screened for new tumors. Computed tomography (CT), magnetic resonance imaging (MRI), digital subtraction angiography (DSA), and functional positron emission tomography (PET) can provide a reliable preoperative diagnosis in the absence of histology. Comparative data on therapeutic outcome and morbidity now render radiation, stereotactic radiosurgery, and active surveillance preferable over surgery in highly advanced cases of jugulotympanic and vagal paragangliomas, whereas surgery remains the first choice for most carotid body paragangliomas.

Complete paraganglioma removal continues to be the primary therapeutic goal; however, this is sometimes impossible to accomplish with acceptable morbidity. In these cases, therapy selection should focus on preserving cranial nerve function and minimizing both tumor-associated and therapy-associated complications, particularly in genetically predisposed patients. An interdisciplinary approach to the management of hereditary head and neck paragangliomas is strongly recommended.
Head and neck squamous cell carcinoma in HIV patients
Authors: Rampinelli Vittorio , Gennarini Francesca , Borsetto Daniele , Piazza Cesare
Published: March 2023

Purpose of review

The introduction of antiretroviral therapy has significantly impacted the incidence of head and neck squamous cell carcinoma (HNSCC) in people living with HIV (PLWH). This manuscript aims to give an overview of the evidence in the literature about this population.

Recent findings

PLWH have an increased incidence of HNSCC, with earlier age and more advanced stage at diagnosis. This epidemiologic trend may be explained by combining traditional and HIV-related risk factors. With the improvement of global health status, more patients are candidate for complex therapeutic strategies with curative intent. To date, it is still debated whether HIV-infected patients possess a profile of increased risk regarding treatment-related toxicity and survival outcomes, with the literature still lacking substantial evidence. Among the prognostic factors that can guide the clinician in selecting the most appropriate treatment strategy, age, site/subsite, stage, HIV viral load, and CD4+ T-cell count at diagnosis are the most relevant.

Pathogenesis, treatment characteristics, oncologic outcomes, and prognostic factors of HNSCC in PLWH are still debated. Given the increasing incidence of HNSCC in PLWH, the need for dedicated evidence-based studies represents a significant research gap to be addressed.
Vagal paragangliomas
Authors: Mottie Lena , Meulemans Jeroen , Vander Poorten Vincent
Published: March 2023

Purpose of review

A vagal paraganglioma is a rare head and neck tumor arising from the paraganglionic tissue within the perineurium of the vagus nerve, anywhere along the course of the nerve. Due to its proximity to the internal carotid artery, the internal jugular vein and the lower cranial nerves, this disorder poses significant diagnostic and therapeutic challenges. The diagnostic workup and management keep on evolving.

Recent findings

This article gives a concise update of the clinical spectrum and the current state-of-the-art diagnostic workup and management of vagal paraganglioma.

Every patient with suspected vagal paraganglioma needs to be evaluated by a multidisciplinary team. The management strategy is selected depending on the growth rate of the tumor, the age and fitness of the patient, the number of affected cranial nerves, the metabolic activity of the paraganglioma, and the eventual multicentricity. An algorithm guiding the clinician through the different treatment options is presented.
The relationship between auditory behaviours and speech and language development in children with cleft lip and palate
Authors: van Eeden Stephanie
Published: March 2023

Purpose of review

Children born with a cleft lip and palate (CLP) are at risk of speech problems. There is a high prevalence of conductive hearing loss due to otitis media with effusion and recent research has highlighted broader difficulties with language and educational attainment. There has been increased interest in the impact of auditory processing on a child's development, but little study into links between auditory skills and speech and language development.

Recent findings

Children with CLP consistently struggle with auditory tasks. Difficulties processing words in a noisy background, auditory attention and temporal processing are frequently reported. A recent study in the United Kingdom investigated the auditory behaviours of 95 children aged 5–8 years with nonsyndromic CLP and compared these with speech and language profiles. Auditory difficulties correlated with speech development and most auditory behaviours correlated with language outcomes. There was also a correlation of language with speech outcomes, suggesting a more complex and interdependent relationship.

Children with CLP present with high levels of difficulties with auditory skills. The potential impact of this on broader development needs further research, but clinicians should ensure that auditory skills beyond the hearing test are monitored, and advice given to parents to minimize the impact.
Open tibial shaft fractures: treatment patterns in sub-Saharan Africa
Authors:   ORCA Study Group
Published: March 2023

Objective:

Open tibial shaft fractures are a leading cause of disability worldwide, particularly in low and middle-income countries (LMICs). Guidelines for these injuries have been developed in many high-income countries, but treatment patterns across Africa are less well-documented.

Methods:

A survey was distributed to orthopaedic service providers across sub-Saharan Africa. Information gathered included surgeon and practice setting demographics and treatment preferences for open tibial shaft fractures across 3 domains: initial debridement, antibiotic administration, and fracture stabilization. Responses were grouped according to country income level and were compared between LMICs and upper middle-income countries (UMICs).

Results:

Responses from 261 survey participants from 31 countries were analyzed, with 80% of respondents practicing in LMICs. Most respondents were male practicing orthopaedic surgeons at a tertiary referral hospital. For all respondents, initial debridement occurred most frequently in the operating room (OR) within the first 24 hours, but LMIC surgeons more frequently reported delays due to equipment availability, treatment cost, and OR availability. Compared with their UMIC counterparts, LMIC surgeons less frequently confirmed tetanus vaccination status and more frequently used extended courses of postoperative antibiotics. LMIC surgeons reported lower rates of using internal fixation, particularly for high-grade and late-presenting fractures.

Conclusions:

This study describes management characteristics of open tibial shaft fractures in sub-Saharan Africa. Notably, there were reported differences in wound management, antibiotic administration, and fracture stabilization between LMICs and UMICs. These findings suggest opportunities for standardization where evidence is available and further research where it is lacking.

Level of Evidence:

VI—Cross-Sectional Study.
PRAME Expression in Mucosal Melanoma of the Head and Neck Region
Authors: Ricci Costantino , Altavilla Maria V. , Corti Barbara , Pasquini Ernesto , Presutti Livo , Baietti Anna M. , Amorosa Luca , Balbi Tiziana , Baldovini Chiara , Ambrosi Francesca , Grillini Marco , D’Errico Antonia , Fiorentino Michelangelo , Foschini Maria P.
Published: March 2023

PRAME (PReferentially expressed Antigen in MElanoma), a cancer-testis antigen expressed in normal and neoplastic tissues with several functions, proved to be a useful diagnostic tool in the differential diagnosis between benign and malignant melanocytic lesions. The current study aims to perform PRAME stain on a retrospective case series of mucosal melanocytic tumors of the head and neck region to compare 3 different scores and evaluate the most reliable one in this diagnostic set. Immunohistochemical analysis for PRAME was performed in 54 benign and malignant mucosal melanocytic tumors of the head and neck region collected from 41 patients. The best-performing cutoff of PRAME-positive cells (nuclear stain) to differentiate benign and malignant mucosal melanocytic tumors of the head and neck region is that proposed by Raghavan and colleagues (<60%/≥60% of PRAME-positive cells), with 100% and 77.8% of benign lesions and malignant tumors respectively correctly identified. Applying this score, PRAME stain showed the best results (sensitivity, specificity, accuracy, and positive and negative predictive values) for the diagnosis of head and neck melanocytic tumors. However, a subset of PRAME-negative malignant tumors was identified, especially located in the palatal area (hard and soft palate). Finally, high PRAME expression (≥60%) was associated with specific sites (nasal cavity/nasal septum/turbinates nasopharynx, and the maxillary sinus), nodular histotype, and female sex.
Endoscopic Assessment and Serial Balloon Dilatation in a Toddler With Dyskeratosis Congenita-Hoyeraal-Hreidarsson Syndrome Following Bone Marrow Transplant: A Case Report
Authors: Rodriguez Kurt , Shargo Ryan , Ekblad Morgan , Sunkersett Gauri , Karjoo Sara , Betensky Marisol , Wilsey Michael J.
Published: March 2023

We report a 3-year-old patient with suspected oropharyngeal graft-versus-host disease (GVHD) who developed progressive dysphagia to solids and liquids. The patient has a history of Dyskeratosis Congenita-Hoyeraal-Hreidarsson Syndrome with associated bone marrow failure requiring a nonmyeloablative matched sibling hematopoietic stem cell transplant. Esophagram revealed significant narrowing in the cricopharyngeal region. Subsequent esophagoscopy showed a proximal, high-grade pinhole esophageal stricture that was very difficult to visualize and cannulate. High-grade esophageal strictures are uncommon in very young children with GVHD. We believe the patient’s underlying Dyskeratosis Congenita-Hoyeraal-Hreidarsson Syndrome in the setting of inflammatory changes seen in GVHD following hematopoietic stem cell transplant set the stage for a high-grade esophageal obstruction. The patient’s symptoms improved with serial endoscopic balloon dilation.
“Lipedema: The use of cultured adipocytes for identification of diagnostic markers”
Authors: Ernst Anna M. , Steiner Marianne , Kainz Verena , Tempfer Herbert , Spitzer Gabriel , Plank Tanja , Bauer Hans-Christian , Bresgen Nikolaus , Habenbacher Andreas , Bauer Hannelore , Lipp Anna-Theresa
Published: March 2023

Background:

Lipedema is a progressive disease, diagnosed most often in women, which is characterized by the unproportionate and symmetrical distribution of adipose tissue primarily in the extremities. Despite numerous results from in vitro and in vivo studies, many questions regarding the pathology and genetic background of lipedema have remained unanswered.

Methods:

Adipose tissue-derived stromal/stem cells (ASCs) were isolated from lipoaspirates derived from non-obese and obese lipedema and non-lipedema donors. Growth/morphology, metabolic activity, differentiation potential and gene expression were evaluated using quantification of lipid accumulation, metabolic activity assay, live-cell imaging, RT-PCR, quantitative PCR and immunocytochemical staining.

Results:

The adipogenic potential of lipedema and non-lipedema ASCs did not rise in parallel with the donors' BMI and did not differ significantly between groups. However, in vitro differentiated adipocytes from non-obese lipedema donors showed significant upregulation of adipogenic gene expression compared to non-obese controls. All other genes tested were equally expressed in lipedema and non-lipedema adipocytes. The ADIPOQ/LEP ratio (ALR) was significantly reduced in adipocytes from obese lipedema donors compared to their non-obese lipedema counterparts. Increased stress fiber-integrated SMA was visible in lipedema adipocytes compared to non-lipedema controls and appeared enhanced in adipocytes from obese lipedema donors.

Conclusions:

Not only lipedema per se but also BMI of donors impact adipogenic gene expression substantially in vitro. The significantly reduced ALR and the increased occurrence of myofibroblast-like cells in “obese” lipedema adipocyte cultures underlines the importance of attention towards the co-occurrence of lipedema and obesity. These are important findings towards accurate diagnosis of lipedema.
Hyperbaric Oxygen Therapy for Threatened Nipple-Sparing Mastectomy Flaps
Authors: Nasr Hani Y. , Rifkin William J. , Muller John N. , Chiu Ernest S.
Published: March 2023

Background

Nipple-sparing mastectomy (NSM) is emerging as the standard of care for treatment of breast cancer because of its oncologic safety and superior aesthetic outcomes. However, ischemia or necrosis of the skin flap and/or nipple-areola complex remain frequent complications. Hyperbaric oxygen therapy (HBOT) has emerged as a potential adjunct for flap salvage, although it is not currently a widely accepted practice. Here we review our institution's experience using a protocol of HBOT in patients with signs of flap ischemia or necrosis after NSM.

Methods

Retrospective review identified all patients treated with HBOT at our institution's hyperbaric and wound care center because of signs of ischemia after NSM. Treatment parameters consisted of 90-minute dives at 2.0 atmosphere once or twice daily. Patients unable to tolerate dives were considered a treatment failure, whereas those lost to follow-up were excluded from analysis. Patient demographics, surgical characteristics, and treatment indications were recorded. Primary outcomes assessed were flap salvage (no operative revision), need for revision procedures, and treatment complications.

Results

A total of 17 patients and 25 breasts met the inclusion criteria. The mean ± SD time to initiation of HBOT was 9.47 ± 12.7 days. The mean ± SD age was 46.7 ± 10.4 years, and mean ± SD follow-up time was 36.5 ± 25.6 days. Indications for NSM included invasive cancer (41.2%), carcinoma in situ (29.4%), and breast cancer prophylaxis (29.4%). Initial reconstruction included tissue-expander placement (47.1%), autologous reconstruction with deep inferior epigastric flaps (29.4%), and direct-to-implant reconstruction (23.5%). Hyperbaric oxygen therapy indications included ischemia or venous congestion for 15 breasts (60.0%) and partial thickness necrosis for 10 breasts (40.0%). Flap salvage was achieved in 22 of 25 breasts (88.0%). Reoperation was required for 3 breasts (12.0%). Hyperbaric oxygen therapy–related complications were observed in 4 patients (23.5%), which included 3 patients with mild ear pain and 1 patient with severe sinus pressure leading to treatment abortion.

Conclusions

Nipple-sparing mastectomy is an invaluable tool for breast and plastic surgeons to achieve oncologic and cosmetic goals. However, ischemia or necrosis of the nipple-areola complex or mastectomy skin flap remains frequent complications. Hyperbaric oxygen therapy has emerged as a possible intervention for threatened flaps. Our results demonstrate the utility of HBOT in this population to achieve excellent NSM flap salvage rates.
Efficacy of Immediate Lymphatic Reconstruction in Prevention of Breast Cancer–Related Lymphedema
Authors: Le Nicole K. , Liu Langfeier , Jesus Cruz Rachel , Parikh Jeegan , Rotatori Robert M. , Wainwright D’Arcy J. , Weinstein Brielle , Tavares Tina , Panetta Nicholas J.
Published: March 2023

Introduction

Breast cancer–related lymphedema (BCRL) is a chronic condition that can negatively affect the quality of life of breast cancer survivors. Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection is emerging as a technique for the prevention of BCRL. This study compared the incidence of BRCL in patients who received ILR and those who were not amenable to ILR.

Methods

Patients were identified through a prospectively maintained database between 2016 and 2021. Some patients were deemed nonamenable to ILR due to a lack of visualized lymphatics or anatomic variability (eg, spatial relationships or size discrepancies). Descriptive statistics, independent t test, and Pearson χ2 test were used. Multivariable logistic regression models were created to assess the association between lymphedema and ILR. A loose age-matched subsample was created for subanalysis.

Results

Two hundred eighty-one patients were included in this study (252 patients who underwent ILR and 29 patients who did not). The patients had a mean age of 53 ± 12 years and body mass index of 28.6 ± 6.8 kg/m2. The incidence of developing lymphedema in patients with ILR was 4.8% compared with 24.1% in patients who underwent attempted ILR without lymphatic reconstruction (P = 0.001). Patients who did not undergo ILR had significantly higher odds of developing lymphedema compared with those who had ILR (odds ratio, 10.7 [3.2–36.3], P < 0.001; matched OR, 14.2 [2.6–77.9], P < 0.001).

Conclusions

Our study showed that ILR was associated with lower rates of BCRL. Further studies are needed to determine which factors place patients at highest risk of developing BCRL.
Bacterial Growth in Unsealed Bone-grafting Products
Authors: Shmuly Tom , Hater Amer , Bar-Ness Greenstein Ronit , Allon Dror Michael
Published: March 2023

Objective:

The aim of this study was to simulate reusing an opened package of bone substitute (BS) under typical clinical conditions, by analyzing bacterial growth in samples of resealed packages of alloplast and xenograft BS following different time periods up to a week.

Materials and Methods:

The experiment was performed in 2 stages: dry stage and wet stage. In the dry stage, BS samples were exposed to air for 15 minutes and then were sealed again in their original package. After several “aging” periods [no aging (t0), 24 hours (t1), and 1 week (t7)], BS samples were plated onto brain heart infusion agar and were incubated at 37 °C for 24 hours under aerobic conditions. Bacterial colonies were enumerated and colony forming units per 1 mL was calculated. In the wet stage, the experiment was repeated but BSs were left to age in a brain heart infusion broth to simulate a more supporting humid environment to encourage bacterial growth.

Results:

In the dry stage of the experiment, no bacterial growth was detected in both xenograft and alloplast samples (colony forming units/mL=0), in any of the time points (t0, t1, t7). In the wet stage, average bacterial growth was 0 for both groups in t0. In t1: 1.14 × 104±4.16 × 103 for the xenograft and 7.73 × 105± 9.99 × 105 for the alloplast. In t7: 1.64 × 109±1.82 × 108 in the xenograft compared with 8.86 × 108±4.00 × 108 for the alloplast. Analysis of variance with repeated measures showed a significant difference in comparison of the 2 BSs for each time group (t1 and t7) (P<0.005).

Conclusion:

Under dry conditions, in a resealed package, there was no bacterial growth for up to 1 week for both BSs. Once the BSs are introduced to a humid environment, which supports bacterial growth, the xenograft BS allowed more rapid bacterial growth, compared with the alloplastic BS.