bluuebunny/crossref_metadata_2025 huggingface dataset:
Telemonitorización en apnea obstructiva del sueño: Una buena estrategia para ahorro de costos en comparación con el seguimiento estándar
Authors: Romero-López Zaira
Published: October 2023

Telemonitoring of obstructive sleep apnea patients is increasingly being adopted though its cost-effectiveness evidence base is scanty. This study investigated whether telemonitoring is a cost-effective strategy compared with the standard follow-up in patients with obstructive sleep apnea who are starting continuous positive airway pressure treatment. In total, 167 obstructive sleep apnea patients were randomised into telemonitoring (n = 79) or standard follow-up (n = 88), initiated continuous positive airway pressure treatment, and were followed up for 6 months. The frequencies of healthcare contacts, related costs (in USD 2021 prices), treatment effect and compliance were compared between the follow-up approaches using generalized linear models. The cost effectiveness analysis was conducted from a healthcare perspective and the results presented as cost per avoided extra clinic visit. Additionally, patient satisfaction between the two approaches was explored. The analysis showed no baseline differences. At follow-up, there was no significant difference in treatment compliance, and the mean residual apnea–hypoapnea index. There was no difference in total visits, adjusted incidence rate ratio 0.87 (0.72–1.06). Participants in the telemonitoring arm made eight times more telephone visits, 8.10 (5.04–13.84), and about 73% fewer physical healthcare visits 0.27 (0.20–0.36). This translated into significantly lower total costs for the telemonitoring approach compared with standard follow-up, -192 USD (-346 to -41). The form of follow-up seemed to have no impact on the extent of patient satisfaction. These results demonstrate the telemonitoring of patients with obstructive sleep apnea initiating continuous positive airway pressure treatment as a cost saving strategy and can be argued as a potential worthy investment.
Elevated Insulin Levels Engage the Salience Network during Multisensory Perception
Authors: Schumann Katja , Rodriguez-Raecke Rea , Sijben Rik , Freiherr Jessica
Published: October 2023

Introduction: Brain insulin reactivity has been reported in connection with systematic energy metabolism, enhancement in cognition, olfactory sensitivity, and neuroendocrine circuits. High receptor densities exist in regions important for sensory processing. The main aim of the study was to examine whether intranasal insulin would modulate the activity of areas in charge of olfactory-visual integration. Methods: As approach, a placebo-controlled double-blind within crossover design was chosen. The experiments were conducted in a research unit of a university hospital. On separate mornings, twenty-six healthy normal-weight males aged between 19 and 31 years received either 40 IU intranasal insulin or placebo vehicle. Subsequently, they underwent 65 min of functional magnetic resonance imaging whilst performing an odor identification task. Functional brain activations of olfactory, visual, and multisensory integration as well as insulin versus placebo were assessed. Regarding the odor identification task, reaction time, accuracy, pleasantness, and intensity measurements were taken to examine the role of integration and treatment. Blood samples were drawn to control for peripheral hormone concentrations. Results: Intranasal insulin administration during olfactory-visual stimulation revealed strong bilateral engagement of frontoinsular cortices, anterior cingulate, prefrontal cortex, mediodorsal thalamus, striatal, and hippocampal regions (p ≤ 0.001 familywise error [FWE] corrected). In addition, the integration contrast showed increased activity in left intraparietal sulcus, left inferior frontal gyrus, left superior frontal gyrus, and left middle frontal gyrus (p ≤ 0.013 FWE corrected). Conclusions: Intranasal insulin application in lean men led to enhanced activation in multisensory olfactory-visual integration sites and salience hubs which indicates stimuli valuation modulation. This effect can serve as a basis for understanding the connection of intracerebral insulin and olfactory-visual processing.
Associations between Antiepileptic Use and Hypogammaglobulinaemia: Findings from a Population-Based Case-Control Study Using Data Linkage
Authors: Perrott Sarah L. , Macleod Angus D.
Published: October 2023

Background and Objectives: Increased mortality in epilepsy due to infections (other than pneumonia) has been demonstrated. Small case series of people on antiepileptic drugs (AEDs) have described hypogammaglobulinaemia, which may predispose to infections. It is unclear whether hypogammaglobulinaemia is more frequent in people on AEDs, what AEDs it is associated with, or what clinical impact it has. In this population-based study, we aimed to determine whether AEDs were associated with hypogammaglobulinaemia, which AEDs were associated, and whether the associations may be causal. Methods: We conducted an unmatched case-control study using data linkage of routinely collected biochemistry, prescribing, and morbidity datasets in North-East Scotland from 2009–2021. Cases were participants with immunoglobulin levels less than the reference range. Controls were those with normal/high immunoglobulin levels. Logistic regression was used to investigate associations between AED exposure and any hypogammaglobulinaemia, adjusting for age, sex, and comorbidity. We also analysed low IgA, IgM, and IgG separately. We analysed “any AED” exposure and common individual drugs separately. Cumulative exposure data were used to determine whether an exposure-response relationship was present. Results: 18,666 cases and 127,157 controls were identified. Use of any AED was associated with increased risk of hypogammaglobulinaemia (adjusted odds ratio [aOR] 1.20 [95% CI: 1.15–1.25]). Phenytoin use was strongly associated with low IgA (aOR 5.90 [95% CI: 3.04, 10.43]). Carbamazepine and lamotrigine were also associated with low IgA. Apart from topiramate, which was associated with a non-significant decrease in odds of hypogammaglobulinaemia, there was a consistent increase in odds of hypogammaglobulinaemia across most AEDs studied. Panhypogammaglobulinaemia was associated with any AED use, carbamazepine, lamotrigine, gabapentin, and multiple AED use. There was evidence of an exposure-response relationship between any AED use and any hypogammaglobulinaemia, low IgA, and low IgG. Carbamazepine and probably lamotrigine also had an exposure-response relationship with any hypogammaglobulinaemia. Discussion: AEDs may increase hypogammaglobulinaemia risk. Specific classes of immunoglobulins are differentially affected, and the exposure-response analysis suggests this may be causal. Further work should investigate the clinical impact of these findings. Clinicians should check immunoglobulin levels if unusual or recurrent infections occur in patients treated with AEDs.
Environmental Impact of Bronchoscopy: Analysis of Waste Mass and Recyclability of Bronchoscopic Equipment and Consumables
Authors: Patrucco Filippo , Gavelli Francesco , Balbo Piero Emilio
Published: October 2023

Background: Greenhouse gases (GHGs) are significant contributors to climate change, and CO2 equivalent (CO2-e) is measured to compare emissions from GHGs. The healthcare sector contributes 4.4% of global CO2-e emissions, mainly with energy consumption and, in lesser extent, waste production. In this regard, bronchoscopy procedures produce a large amount of waste and are responsible for a significant consumption of energy. Objective: We aimed at quantifying the impact on waste mass production, energy consumption, and recyclability of bronchoscopic procedures. Methods: We conducted a prospective single-centre observational study; for each type of procedure (performed with either reusable or single-use instruments), the number of items used, their weight, and recyclability were evaluated, as well as the material of which recyclable waste was made of. We then calculated the total amount of waste produced, its recyclability, energy consumption, and CO2-e produced over 10 days of activity in our Interventional Pulmonology Unit. Results: Sixty procedures generated 61,928 g of waste, of which only 15.8% was potentially recyclable. Single-use instruments generated nearly twofold more recyclable waste than reusable ones, 80% during the procedure phase. Reusable instruments generated 45% of waste during the reprocessing phase, of which 50% was recyclable. The recyclable material was totally composed of paper and plastic. During 10 days of activity, we consumed 64 kWh and produced more than 67 kg of CO2-e due to non-recyclable waste and energy consumption. Conclusions: Our results confirm the compelling need to recycle as many materials as possible, even if the amount of recyclable waste is limited. In this respect, official documents issued by international societies are urgently needed to align our activity with climate requirements and improve the sustainability of our work.
An Unexpected Cause of Raised Procalcitonin
Authors: Sabahat Uzma , Thomas Liza Mariam , Shaikh Niaz Ahmed , Ali Nageen Murad
Published: October 2023

A 28-year-old female was admitted to hospital with a history of paracetamol overdose, a total of 18 g, 2 days prior to presentation. Other than nausea and mild abdominal pain she had no other symptoms and systemic examination was unremarkable. Laboratory tests showed slightly elevated liver enzymes and significantly elevated procalcitonin level of 97 ng/mL (normal <0.05 ng/mL). This septic biomarker was alarmingly high, though the patient had no clinical features of infection, and C-reactive protein – the other routinely done marker of inflammation – was normal. She received treatment with N-acetylcysteine for paracetamol overdose. Other than slightly elevated liver enzymes, tests of liver function were essentially normal. All investigations for underlying infection were negative. She had a short uncomplicated 5-day hospital stay. Her procalcitonin levels improved spontaneously and were significantly reduced though not yet normal at the time of discharge.
Expanding the Phenotypic and Genotypic Spectrum of Weaver Syndrome: A Missense Variant of the EZH2 Gene
Authors: Kendir-Demirkol Yasemin , Yeter Burcu , Jenny Laura A.
Published: October 2023

Introduction: Weaver syndrome (WS) is a rare autosomal dominant disorder characterized by distinctive facial features, pre- and post-natal overgrowth, macrocephaly, and variable developmental delay. The characteristic facial features are ocular hypertelorism, a broad forehead, almond-shaped palpebral fissures and, in early childhood, large, fleshy ears, a pointed “stuck-on” chin with horizontal skin creases, and retrognathia. Heterozygous pathogenic/likely pathogenic variants in the enhancer of zeste homolog 2 (EZH2) gene are responsible for WS. Case Presentation: Here, we report a male patient with a heterozygous likely pathogenic variant in EZH2 gene who has tall stature, distinctive facial features, mild development delay, hypoxic-ischemic encephalopathy with a MRI finding of periventricular leukomalacia, gingival hypertrophy, and early onset high hypermetropia. Conclusion: This case demonstrates the importance of reporting detailed molecular and clinical findings in patients to expand the genotypic and phenotypic findings of this rare syndrome.
Circulating Metabolites and Cardiovascular Disease in Asians with Chronic Kidney Disease
Authors: Cai Jiashen , Chong Crystal Chun Yuen , Cheng Ching Yu , Lim Cynthia Ciwei , Sabanayagam Charumathi
Published: October 2023

Introduction: Chronic kidney disease (CKD) is a growing public health problem, with significant burden of cardiovascular disease and mortality. The risk of cardiovascular disease in CKD is elevated beyond that predicted by traditional cardiovascular risk factors, suggesting that other factors may account for this increased risk. Through metabolic profiling, this study aimed to investigate the associations between serum metabolites and prevalent cardiovascular disease in Asian patients with CKD to provide insights into the complex interactions between metabolism, cardiovascular disease and CKD. Methods: This was a single-center cross-sectional study of 1,122 individuals from three ethnic cohorts in the population-based Singapore Epidemiology of Eye Disease (SEED) study (153 Chinese, 262 Indians, and 707 Malays) aged 40–80 years with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2). Nuclear magnetic resonance spectroscopy was used to quantify 228 metabolites from the participants’ serum or plasma. Prevalent cardiovascular disease was defined as self-reported myocardial infarction, angina, or stroke. Multivariate logistic regression identified metabolites independently associated with cardiovascular disease in each ethnic cohort. Metabolites with the same direction of association with cardiovascular disease in all three cohorts were selected and subjected to meta-analysis. Results: Cardiovascular disease was present in 275 (24.5%). Participants with cardiovascular disease tend to be male; of older age; with hypertension, hyperlipidemia, and diabetes; with lower systolic and diastolic blood pressure (BP); lower high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol than those without cardiovascular disease. After adjusting for age, sex, systolic BP, diabetes, total cholesterol, and HDL cholesterol, 10 lipoprotein subclass ratios and 6 other metabolites were significantly associated with prevalent cardiovascular disease in at least one cohort. Meta-analysis with Bonferroni correction for multiple comparisons found that lower tyrosine, leucine, and valine concentrations and lower cholesteryl esters to total lipid ratio in intermediate-density lipoprotein (IDL) were associated with cardiovascular disease. Conclusion: In Chinese, Indian, and Malay participants with CKD, prevalent cardiovascular disease was associated with tyrosine, leucine, valine, and cholesteryl esters to total lipid ratios in IDL. Increased cardiovascular risk in CKD patients may be contributed by altered amino acid and lipoprotein metabolism. The presence of CKD and ethnic differences may affect interactions between metabolites in health and disease, hence greater understanding will allow us to better risk stratify patients, and also individualize care with consideration of ethnic disparities.
Diverging Trends in the Incidence of Spontaneous Intracerebral Hemorrhage in Sweden 2010–2019: An Observational Study from the Swedish Stroke Register (Riksstroke)
Authors: Drescher Conrad , Buchwald Fredrik , Ullberg Teresa , Pihlsgård Mats , Norrving Bo , Petersson Jesper
Published: October 2023

Introduction: Although ischemic stroke incidence has decreased in Sweden over the past decade, trends in spontaneous intracerebral hemorrhage (ICH) incidence are less well delineated. In this time period, there has been a dramatic increase in use of oral anticoagulants (OAC). The aim of our study was to investigate incidence trends in spontaneous first-ever ICH in Sweden between 2010 and 2019, with a focus on non-OAC-associated and OAC-associated ICH. Methods: We included patients (≥18 years) with first-ever ICH registered in the hospital-based Swedish Stroke Register (Riksstroke) 2010–2019. Data were stratified by non-OAC and OAC ICH and analyzed for 2010–2012, 2013–2016, and 2017–2019. Incidence rates are shown as crude and age-specific per 100,000 person-years. Results: Between 2010 and 2019, 22,289 patients with first-ever ICH were registered; 18,325 (82.2%) patients with non-OAC ICH and 3,964 (17.8%) patients with OAC ICH. Annual crude incidence (per 100,000) of all first-ever ICH decreased by 10% from 29.5 (95% CI 28.8–30.3) to 26.7 (95% CI 26.0–27.3) between 2010–2012 and 2017–2019. The crude incidence rate of non-OAC ICH decreased by 20% from 25.7 (95% CI 25.0–26.3) to 20.7 (95% CI 20.1–21.2), whereas OAC ICH increased by 56% from 3.86 (95% CI 3.61–4.12) to 6.01 (95% CI 5.70–6.32). The proportion of OAC ICH of all first-ever ICH increased between 2010–2012 and 2017–2019 from 13.1% to 22.5% (p < 0.001). Proportional changes were largest in the age group ≥85 years with a decrease in non-OAC ICH by 32% from 155 (95% CI 146–164) to 106 (95% CI 98.6–113) and an increase in OAC ICH by 155% from 25.7 (95% CI 22.1–29.4) to 65.5 (95% CI 59.9–71.2). Conclusion: Incidence of first-ever ICH in Sweden decreased by 10% between 2010 and 2019. We found diverging trends with a 20% decrease in non-OAC-associated ICH and a 56% increase in OAC-associated ICH. Further research on ICH epidemiology, analyzing non-OAC and OAC-associated ICH separately, is needed to follow up these diverging trends including underlying risk factors.
Thrombin Decrease in Thrombin Generation after Heparin Administration in a Homozygous Type II Heparin-Binding Site Antithrombin-Deficient Pregnant Woman
Authors: Malíková Ivana , Husáková Martina , Bílková Jana , Brzežková Radka , Kvasnička Tomáš
Published: October 2023

Objectives: There is a major problem in providing prophylactic treatment in antithrombin (AT)-deficient pregnant women with a homozygous mutation of the heparin-binding site and AT level of 17%. The aim of the study was to determine the effectiveness of heparin by monitoring changes in thrombin generation (TG) in vitro so that pregnant women are not exposed to stress in vivo. Methods: We used the chromogenic method for determination of factor Xa (FXa) inhibition for enoxaparin, nadroparin, dalteparin, fondaparinux, and unfractionated heparin and the thrombin generation assay. Results: We found that the degree of inhibition is very different when different heparins are compared. Nadroparin reduces TG, the most compared to low molecular weight heparins (LMWHs). Conclusion: Routine monitoring of anti-FXa activity should be supplemented with TG monitoring, where the effect of LMWH does not manifest itself as this could help in estimating thrombophilic risk during pregnancy.
Feminizing Adrenocortical Tumor with Multiple Recurrences: A Case Report
Authors: Rich Joseph M. , Duddalwar Vinay , Cheng Phillip M. , Aron Manju , Daneshmand Siamak
Published: October 2023

Feminizing adrenocortical tumors (FATs) are exceptionally rare primary adrenal neoplasms that cause high estrogen and low testosterone levels. They are most common in adult males, typically presenting with gynecomastia, hypogonadism, and weight loss. They are almost always malignant, with a poor prognosis and a high recurrence rate. We report a case of a 35-year-old man with an adrenal FAT with high estrogen (181 pg/mL) and low testosterone (37 ng/dL) who presented with gynecomastia, erectile dysfunction, subclinical Cushing syndrome, and pain localizing to different regions of the torso. There was no evidence of metastatic disease initially as seen by visualization of a well-marginated mass on computed tomography scan. Surgical resection of the FAT was performed, and the mass was confirmed to be a low-grade tumor. Clinical symptoms were resolved after surgery. Despite complete resection with negative margins, the patient subsequently had two separate local metastatic recurrences within a few years, treated with a combination of further surgery and medical intervention. This case highlights the unique features of an exceedingly rare adrenal tumor and stresses the importance of early detection and vigilant surveillance following resection due to high recurrence rates.
Antibiotics May Interfere with Nivolumab Efficacy in Patients with Head and Neck Squamous Cell Carcinoma
Authors: Ueta Reio , Imai Hiroo , Saijo Ken , Kawamura Yoshifumi , Kodera Shuto , Komine Keigo , Ouchi Kota , Kasahara Yuki , Taniguchi Sakura , Yoshida Yuya , Sasaki Keiju , Shirota Hidekazu , Takahashi Masanobu , Ishioka Chikashi
Published: October 2023

Introduction: Patients with the head and neck squamous cell carcinoma (SCC) are often treated with immune checkpoint inhibitors (ICIs). Recently, antibiotic intake was reported to lower the efficacy of ICIs in patients with several types of cancers. However, it is unclear if antibiotics affect the efficacy of ICIs in patients with head and neck SCC. We retrospectively assessed the influence of antibiotics on the treatment efficacy of nivolumab, an ICI, in patients with head and neck SCC. Methods: We reviewed the medical records of patients with head and neck SCC treated with nivolumab at the Department of Medical Oncology, Tohoku University Hospital, between 2017 and 2021. Patients who received oral or intravenous antibiotics from a month before the day of nivolumab initiation to the day of the first imaging evaluation of ICI efficacy were assigned to the antibiotic-treated group. The remaining patients were assigned to the antibiotic-untreated group. The response rate (RR), progression-free survival (PFS), and overall survival time (OS) of both groups were compared. Results: Forty-five patients were assigned to the antibiotic-treated group and 19 to the antibiotic-untreated group. The RR, median PFS, and median OS of the antibiotic-treated group were 23.7%, 3.2 months (95% confidential interval [CI]: 2.0–4.1), and 8.4 months (95% CI: 5.3–15.1) and those of the antibiotic-untreated group were 42.1%, 5.8 months (95% CI: 2.3–16.7), and 18.4 months (95% CI: 6.2–23.1), respectively. The PFS of the antibiotic-untreated group was significantly longer than that of the antibiotic-treated group. Conclusion: Our findings indicate that antibiotic treatment significantly shortens the PFS with nivolumab therapy in patients with head and neck SCC.
5G-Based Remote Virtual Bronchoscopic Navigation-Guided Transbronchial Lung Biopsy for Diagnosis of Lung Cancer: Description of 2 Cases
Authors: Huang Junfeng , Lin Jinsheng , Chen Chongxiang , Liang Weiquan , Chen Yumei , Li Hongjia , Zhong Changhao , Li Shiyue
Published: October 2023

Introduction: Bronchoscopic navigation combined with endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) is an important approach for the diagnosis of peripheral pulmonary lesions (PPL). The fifth-generation (5G) network, characterized by low latency and high stability, has shown promising possibilities in telemedicine for remote areas. Methods: We present two cases of PPL in primary hospitals without navigation equipment. The EBUS-TBLB was performed with the guidance of remote augmented reality virtual bronchoscopic navigation (VBN) based on a 5G network. In practice, the 5G network could enable the matching of actual/virtual bronchoscopic images and navigation paths in real time, as well as high-speed transmission at long distances (>20 km), without any visual delay (<500 ms). Conclusion: Both patients were successfully diagnosed with lung cancer after accurate positioning and obtaining biopsies of target lesions. This 5G-based remote VBN-guided EBUS-TBLB appears to be safe with reliable connections in both cases and shows potential for cost-effectiveness. It would be an optimal resource for undeveloped regions and/or regions lacking endoscopists with extensive experience in navigation-related procedures.
Triple-A Syndrome in Morocco: Founder Effect, Age Estimation of the AAAS c.1331+1G>A Variant, and Implications for Genetic Diagnosis
Authors: Belmokhtar Karam Yahya , Cherkaoui Imane , Lhousni Saida , Elidrissi Errahhali Mounia , Elidrissi Errahhali Manal , Charif Majida , Boulouiz Redouane , Ouarzane Meryem , Elouali Aziza , Ghanam Ayad , Babakhouya Abdeladim , Rkain Maria , Benajiba Noufissa , Bellaoui Mohammed
Published: October 2023

Introduction: Triple-A syndrome (Triple-A) is an autosomal recessive disorder characterized by alacrimia, achalasia, and adrenal insufficiency. Several variants on the AAAS gene have been described, and some variants are clustered in particular geographical areas, such as the c.1331+1G>A variant which is very frequent in North Africa. Here, we describe the genetic features of Triple-A in a series of unrelated families from Morocco. Methods: Screening for the AAAS c.1331+1G>A variant was performed by direct sequencing or by PCR-RFLP. Haplotype analysis using Single Tandem Repeat (STR) markers flanking AAAS gene was performed in order to evaluate the founder effect and estimate the age of the c.1331+1G>A variant. Results: Seven unrelated families with ten individuals clinically diagnosed with Triple-A were evaluated for sequence variations in the AAAS gene. The median age at diagnosis was 3 years, with a range between 2 and 11 years. Molecular analysis revealed that all patients were homozygous for the c.1331+1G>A variant. This variant was not found in 200 healthy controls, indicating that carriers are very rare in the general Moroccan population. Subsequently, STR marker analysis revealed a founder effect and that the most recent common ancestor of Triple-A patients in Morocco would have lived 125 years ago. Conclusion: This is the largest series of Triple-A in Morocco. The same AAAS c.1331+1G>A variant was found in all patients, suggesting a founder effect in Morocco which was subsequently confirmed by microsatellite marker analysis. Therefore, this variant should be systematically investigated to diagnose Triple-A in Morocco.
Reimbursement in the Context of Precision Oncology Approaches in Metastatic Breast Cancer: Challenges and Experiences
Authors: Pixberg Constantin , Schulze Markus , Buschhorn Lars , Suppelna Jan Philip , Mock Andreas , Hlevnjak Mario , Heublein Sabine , Schumacher-Wulf Eva , Schneeweiss Andreas
Published: October 2023

Background: Precision oncology programs using next-generation sequencing to detect predictive biomarkers are extending therapeutic options for patients with metastatic breast cancer (mBC). Regularly, based on the recommendations of the interdisciplinary molecular tumor board (iMTB), an inclusion in a clinical trial is not possible. In this case, the German health insurance system allows for the application of reimbursement for an off-label drug use. Here, we describe the current challenges and our experience with reimbursement of molecular therapies in mBC. Methods: A total of 100 applications for reimbursement of off-label therapies recommended by an iMTB were filed for patients with mBC, of which 89 were evaluable for this analysis. The approval rate was correlated with the molecular level of evidence of the respective therapy according to the National Center for Tumor Diseases (NCT) and European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) classification as well as with pretreatment therapy lines. Findings: Overall, 53.9% (48/89) of reimbursement applications were approved. Applications for therapies based on level of evidence m1 (NCT classification), tier I and II (ESCAT classification) had a significantly and clinically relevant increased chance of reimbursement, while a greater number of previous treatment lines had no significantly increased chance of approval, though a trend of approval toward higher treatment lines was detectable. Interpretation: Currently, the German jurisdiction seems to aggravate the clinical implementation of clinically urgently needed molecular therapies.
Computed Tomography-Defined Body Composition as Prognostic Parameter in Acute Mesenteric Ischemia
Authors: Schwartner Christoph , Mehdorn Matthias , Gockel Ines , Struck Manuel Florian , Leonhardi Jakob , Rositzka Markus , Ebel Sebastian , Denecke Timm , Meyer Hans-Jonas
Published: October 2023

Introduction: Body composition comprising low-skeletal muscle mass (LSMM) and subcutaneous and visceral adipose tissue (SAT and VAT) can be assessed by using cross-sectional imaging modalities. Previous analyses suggest that these parameters harbor prognostic relevance in various diseases. Aim of this study was to analyze possible associations of body composition parameters on mortality in patients with clinically suspected acute mesenteric ischemia (AMI). Methods: All patients with clinically suspected AMI were retrospectively assessed between 2016 and 2020. Overall, 137 patients (52 female patients, 37.9%) with a median age of 71 years were included in the present analysis. For all patients, the preoperative abdominal computed tomography (CT) was used to calculate LSMM, VAT, and SAT. Results: Overall, 94 patients (68.6%) of the patient cohort died within 30 days within a median of 2 days, range 1–39 days. Of these, 27 patients (19.7%) died within 24 h. According to the CT, 101 patients (73.7%) were classified as being visceral obese, 102 patients (74.5%) as being sarcopenic, and 69 patients (50.4%) as being sarcopenic obese. Skeletal muscle index (SMI) was lower in non-survivors compared to survivors (37.5 ± 12.4 cm2/m2 vs. 44.1 ± 13.9 cm2/m2, p = 0.01). There were no associations between body composition parameters with mortality in days (SMI r = 0.07, p = 0.48, SAT r = −0.03, p = 0.77, and VAT r = 0.04, p = 0.68, respectively). In Cox regression analysis, a nonsignificant trend for visceral obesity was observed (HR: 0.62, 95% CI: 0.36–1.05, p = 0.07). Conclusion: SMI might be a valuable CT-based parameter, which could help discriminate between survivors and non-survivors. Further studies are needed to elucidate the associations between body composition and survival in patients with AMI.
Is Frailty Different in Younger Adults Compared to Old? Prevalence, Characteristics, and Risk Factors of Early-Life and Late-Life Frailty in Samples from Sweden and UK
Authors: Bai Ge , Wang Yunzhang , Mak Jonathan K.L. , Ericsson Malin , Hägg Sara , Jylhävä Juulia
Published: October 2023

Introduction: Although frailty is commonly considered as a syndrome of old individuals, recent studies show that it can affect younger adults, too. Whether and how frailty differs in younger adults compared to old is however unknown. To this end, we analyzed the prevalence, characteristics, and risk factors of early-life (aged <65) and late-life (aged ≥65) frailty. Methods: We analyzed individuals in the UK Biobank (N = 405,123) and Swedish Screening Across the Lifespan Twin (SALT; N = 43,641) study. Frailty index (FI) scores ≥0.21 were used to demarcate frailty. Characteristics of early-life versus late-life frailty were analyzed by collating the FI items (deficits) into domains and comparing the domain scores between younger and older frail individuals. Logistic regression was used to assess the risk factors of frailty. Results: The pooled prevalence rates of frailty were 10.3% (95% confidence interval [CI]: 2.7–32.7), 14.4% (95% CI: 4.5–37.2), 19.2% (95% CI: 2.5–68.5) in individuals aged ≤55, 55–64, 65–74, respectively. Younger frail adults (aged <65) had higher scores in immunological, mental wellbeing, and pain-related domains, whereas older frail adults (aged ≥65) had higher scores in cardiometabolic, cancer, musculoskeletal, and sensory-related domains. Higher age, female sex, smoking, lower alcohol consumption, lower education, obesity, overweight, low income, and maternal smoking were similarly associated with the risk of early-life and late-life frailty. Conclusion: Frailty is prevalent also in younger age groups (aged <65) but differs in some of its characteristics from the old. The risk factors of frailty are nevertheless largely similar for early-life and late-life frailty.
Diagnostic Value and Challenges of BRAF V600E Molecular Testing and Thyroid Fine-Needle Aspiration Cytology: A Retrospective Study from a Tertiary Institution in Southern Hunan Province, China
Authors: Lan Zhihua , Yang Fang , Zhang Jing , Lan Ya , Li Hongtao , He Rongfang
Published: October 2023

Introduction: Combined thyroid fine-needle aspiration (FNA) cytology and valine-to-glutamate substitution at codon 600 of B-Raf proto-oncogene, serine/threonine kinase (BRAF V600E) mutation detection are procedures used for diagnosing thyroid nodules in many Chinese tertiary institutions. This retrospective study at our institution aimed to explore the effectiveness and challenges of the combined approach in diagnosing thyroid nodules and the correlation between BRAF V600E mutation status and behavior of papillary thyroid carcinoma. Methods: Thyroid FNA cytology and BRAF V600E mutation detection results were reviewed between November 2020 and July 2022. A total of 623 patients, each of whom underwent thyroidectomy and final pathological examination after FNA cytology diagnosis, were included in the study. The relationship between the BRAF V600E mutational status and pathological parameters was analyzed using the χ2 test. The effectiveness and challenges of FNA cytology alone and the combined procedure were also evaluated based on the final pathology. Results: Of 623 patients, 591 were diagnosed with papillary thyroid carcinoma (PTC), of which 456 were positive for the BRAF V600E mutation. It demonstrated near-perfect specificity for identifying PTC, and its incidence rate showed an age-specific curve with an inverted U-shaped distribution. The final pathological examination showed that the combined procedure had a higher sensitivity (83.91%) than FNA cytology alone (63.45%) for distinguishing PTC from other lesions (p < 0.001). Mutational status was associated with a larger maximum tumor diameter (p = 0.003) and a tendency of capsular invasion (p = 0.0542) but possibly unrelated to central lymph node metastasis (p = 0.1846). Nodular goiters accounted for most benign entities initially designated as Bethesda categories III–V. Conclusion: BRAF V600E mutational analysis complements cytopathology and improves the PTC detection rate in FNA cytology samples due to the high prevalence of the mutation in China. BRAF V600E mutation does not show a statistical correlation with tumor aggressiveness. Morphological pitfalls such as histocyte aggregation, cystic-lining cells in nodular goiters, and oncocytes in Hashimoto’s thyroiditis, were overwhelmingly found in BRAF V600E-negative specimens.
Giant Mature Ovarian Cystic Teratoma in a Pediatric Patient: Case Report and Literature Review
Authors: Barragán-Curiel Adolfo Eduard , Murillo-Zepeda Carlos , Castro-Perez Karla Fernanda , Alcalá-Aguirre Francisco Omar , Díaz-Montoya Lilian Sabinne , Ruiz-Félix Omar Alfonso , Acevedo-Delgado José Antonio , Velasco-Preciado Moyra
Published: October 2023

Mature cystic teratomas, also called dermoid cysts, are the most common germ-cell ovarian neoplasms in children. On average, ovarian dermoid cysts are slow-growing neoplasms with a mean size between 6.4 and 7.0 cm that enlarge at a rate of 1.8 mm/year; however, these can reach large dimensions. Giant ovarian tumors are defined as those having a maximum diameter equal to or more than 15 cm; these represent a therapeutic challenge as they increase the risk of wide wound size and surgical invasiveness. In this paper, we present a case of a 10-year-old Hispanic female that complained of abdominal pain, distension, and nausea. Physical examination revealed a mass on the left side of the abdomen and an axial computed tomography found a large pelvic tumor extending to the abdominal region. After a laparotomy approach, pathology evaluation confirmed the diagnosis of mature cystic teratoma. The patient recovered thoroughly and had no complications at a 6-month follow-up. We conducted a literature review including English and Spanish reports about giant ovarian teratomas; we retrieved 16 cases from 2003 to 2023. We concluded that giant ovarian tumors may be underreported, particularly in resource-limited areas where tumors might grow unrecognized, and that English-language bias might play a substantial role in literature reviews involving case reports and case series.
Endocrine Therapy: From Ovarian Ablation to Individualized Therapy and Signal Inhibition
Authors: Jackisch Christian , Argyriadis Athanasios
Published: October 2023

Background: At the end of the 19th century, Sir George Thomas Beatson first discovered the positive influence of a bilateral oophorectomy on the development of breast cancer lesions in women with advanced disease. Since then, endocrine therapy has been a key component of the treatment of both early (EBC) and advanced-stage (MBC) hormone receptor (HR)-positive breast cancer. Summary: This review discusses the evolution of this therapeutic approach from the introduction of high-dose estrogen therapy leading to the development of several antiestrogen therapies. Recently, the new generation of drugs includes selective estrogen receptor modulators, orally administered selective estrogen receptor degraders (SERDs), as well as more unique agents such as complete estrogen receptor antagonists, proteolysis targeting chimeric, and selective estrogen receptor covalent antagonists. These drugs are under evaluation in various levels of randomized clinical trials (RCTs) being evaluated in both early and metastatic settings. As of today, the options in EBC are ranging from short-term neoadjuvant endocrine therapy to monitor the responsiveness of Ki-67 to combined endocrine therapy in MBC, introducing the combination of endocrine therapy and CDK4/6 inhibition as well as PARP inhibition in patients with luminal breast cancer presenting with germline BRCA1/2 mutations. The results of global RCTs are settled in global and local guidelines to optimize the individual therapy of our patients with luminal EBC. Key Messages: Endocrine intervention in hormone-sensitive breast cancer remains one of the most important options in all settings of early and metastatic breast cancer.
Outcomes after Proton Beam Irradiation in Patients with Choroidal Melanoma Eligible for Investigational AU-011 Treatment
Authors: Wu Frances , Lane Anne Marie , Trofimov Alexei , Shih Helen A. , Gragoudas Evangelos S. , Kim Ivana K.
Published: October 2023

Introduction: Vision loss is common in patients treated with radiotherapy for uveal melanoma. With proton beam irradiation (PBI), the prescribed dose is delivered to the tumor with a sharp dose reduction outside the target volume. However, radiation complications are likely to develop when tumors are located near the optic nerve or fovea. Treatment with light-activated AU-011 (belzupacap sarotalocan), an investigational drug which specifically targets tumor cells, may avoid these complications. We evaluated outcomes in a historical group of patients who fit eligibility criteria for AU-011 therapy and were treated with PBI. Methods: A consecutive series of patients who received PBI for small choroidal melanoma at a single center between 1986 and 2016 were identified. Consistent with eligibility criteria in clinical trials of AU-011, patients were included when tumor dimensions did not exceed 2.5 mm in maximum thickness and 10.0 mm in largest basal diameter (LBD). Snellen visual acuities were converted to logMAR for analysis. Visual acuity outcomes were analyzed in patients with an initial acuity of logMAR 0.7 or better (equivalent to Snellen 20/100). Rates of visual acuity loss and mortality were calculated using the Kaplan-Meier method. Acuity loss by tumor location was compared using log-rank testing. Rates of tumor recurrence, neovascular glaucoma (NVG), and eye loss were also described. Results: Two hundred and 22 patients were included in the study. The median age was 60.7 years (range 21.3–94.8 years). Median tumor thickness was 2.0 mm (range 1.2–2.5 mm), and median LBD was 8.0 mm (range 4.0–10.0 mm). Median follow-up was 6.9 years (range 1.0–30.2 years). In 204 patients with a baseline logMAR visual acuity of 0.7 or better, the mean baseline acuity was 0.15 (equivalent to Snellen 20/25), which decreased to 0.52 (approximately Snellen 20/70) by 5 years after PBI. Visual outcomes were significantly worse for patients with tumors located within 3 mm of the optic disc and/or fovea. Tumor recurrence (1.4%), NVG (4.5%), and eye loss (2.7%) were uncommon. Discussion: Despite the advantageous dose distribution of protons, over half of patients with small choroidal melanomas located near the optic disc or fovea had a visual acuity equivalent to 20/80 or worse at 5 years after PBI. Treatment with AU-011 may allow better vision preservation in small tumors that carry a high risk of vision loss with radiotherapy.
A Retrospective Analysis of the Clinicopathological Features of Patients with Tuberculous Mastitis: A Single Institution’s Experience
Authors: Olmesdahl Nine-Paula , Nel Carolina , Mannell Aylwyn , Fatman Luvo
Published: October 2023

Introduction: Tuberculosis remains a global health burden, especially in low- and middle-income countries. Breast tuberculosis is a rare disease with minimal research available. This disease produces a diagnostic challenge as the clinical presentation is variable, and diagnosis often requires additional investigations. This study was undertaken to determine the efficacy of cytology and histology, together with ancillary studies, in diagnosing tuberculous mastitis. Methods: This retrospective study was conducted in a Johannesburg Hospital over 5 years. Thirty-two patients with confirmed tuberculous mastitis were included. The patients were considered positive for tuberculous mastitis if histological or cytological findings were confirmed with either a positive tuberculosis culture, Ziehl-Neelsen stain, or polymerase chain reaction examination/GeneXpert. Results: This case series comprises 3 males and 29 females with a mean age of 35.66. A breast mass was the most common presentation. Over these 5 years, more biopsies were performed on inflammatory breast lesions than fine needle aspirations. There was a higher confirmation rate for cytology diagnoses compared to histology diagnoses. Conclusion: This study supports using fine needle aspiration combined with GeneXpert as the primary diagnostic modality in diagnosing tuberculous mastitis. This test combination is advantageous in resource- and financially constrained environments as it is relatively simple to perform, cost-effective, and has a rapid turnaround time.
Fluoride Varnish in Dentistry: A Bibliometric Analysis of the 100 Most-Cited Papers
Authors: Zendron Mariana Perini , Rocha Aurélio de Oliveira , Simões Melissa Santos da Silva , Santana Carla Miranda , Bolan Michele , Cardoso Mariane
Published: October 2023

A highly cited paper is a milestone and might impact research and clinical practice. The present study analyzed the 100 most-cited papers on fluoride varnishes in dentistry. A search was performed on July 20, 2022, on the Web of Science Core Collection. Two independent researchers extracted the following data: number and citation density; year and journal of publication; study design; main topic; authors; institutions; keywords; countries and continents. Scopus and Google Scholar were consulted to compare the number of citations. Bibliometric networks were generated in the VOSviewer. The number of citations ranged from 36 to 351, and thirteen papers were cited more than 100 times. The papers were published between 1977 and 2018, most of which were published after 2008 (48%). The most prevalent journal was Caries Research (17%). Intervention studies were the most common design (41%). The most discussed topics were dental caries prevention (48%) and dental remineralization (31%). Europe was the continent with the highest number of publications (46%), mainly from Sweden (14%), and Umea University had the most substantial number of studies (8%). Petersson L.G. was the author with more papers in the top 100 (6%). The most used keywords were “dental caries” (34%) and “fluoride varnish” (31%). It can be concluded that the top 100 cited papers on fluoride varnish primarily originated from Europe, with the majority consisting of intervention studies focusing on the utilization of fluoride varnish for the prevention of dental caries.
Sympathetic Nerve Activation in Acute Kidney Injury and Cardiorenal Syndrome
Authors: Doi Kent , Matsuura Ryo
Published: October 2023

The interactions between the kidney and heart are well studied and frequently lumped together as cardiorenal syndrome. It is believed that the sympathetic nervous system is involved in the mechanism of kidney injury caused by heart failure, but direct evidence is still lacking. In chronic renal fibrosis, sympathetic nerve activation was demonstrated to be harmful by unilateral ureteral obstruction and post-ischemia reperfusion injury models. On the other hand, sympathetic nerve activation seemed protective in acute kidney injury models such as ischemia reperfusion injury and lipopolysaccharide injection. Our recent investigation showed that post-ischemic renal fibrosis was attenuated when preexisting heart failure was induced by transverse aortic constriction surgery and renal denervation canceled this protection. These findings suggest sympathetic nerve activation in cardiorenal syndrome may be protective on chronic renal fibrosis development caused by ischemic an insult.
Bone Dysregulation in Acute Kidney Injury
Authors: Neyra Javier A. , Moe Orson W.
Published: October 2023

Acute kidney injury (AKI) is a highly prevalent condition with multiple acute and chronic consequences. Survivors of AKI are at risk of AKI-to-chronic kidney disease (CKD) transition, which carries significant morbidity and mortality. One retrospective analysis showed increased risk of bone fracture post-AKI in humans, which was independent of CKD development. While there are several theoretical reasons for late disturbances of bone health post-AKI, no definitive data are available to date. An important question is whether there are bone sequelae from AKI that are independent of CKD, meaning bone disease prior to the onset, or in the absence of CKD – a form of “post-AKI osteopathy.” While preclinical studies examining bone health after acute stressors have focused mostly on sepsis models, multiple experimental AKI models are readily available for longitudinal bone health interrogation. Future research should be tailored to define whether AKI is a risk factor, independent of CKD, for bone disease and if present, the time course and type of bone disease. This review summarizes a fraction of the existing data to provide some guidance in future research efforts.
Chronische Prurigo: Innovative Therapien und schneller Wirkungseintritt bieten Hoffnung für Patienten
Authors: Pereira Manuel P.
Published: October 2023

Background: Patients with prurigo nodularis (PN) have multiple itchy nodules, impaired quality of life and sleep deprivation. Prurigo nodularis patients have a high burden of disease, primarily due to the intensity of the itch. It is reasonable to expect that rapid relief of itch – and associated improvement of sleep – are highly valued clinical outcomes for patients. Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN. Objectives: To evaluate the onset of action of nemolizumab on itch and sleep disturbances. Methods: Post hoc analysis of a phase 2 trial of nemolizumab 0.5 mg/kg SC vs. placebo in patients (n = 70) with moderate-to-severe PN (≥20 nodules) and severe pruritus (NRS ≥ 7). Time to significant reduction was assessed for peak pruritus (PP) and sleep disturbance (SD) using numerical rating scales (NRS), also assessed was scratching time during sleep. Results: Nemolizumab significantly reduced itch vs. placebo within 48 h (PP NRS −19.5% vs. −5.8%, respectively, P = 0.014). Significant difference between nemolizumab and placebo in reducing itch by ≥4 on PP NRS was achieved at Day 3 (23.5% vs. 0%, P < 0.001). A significant difference in SD NRS was reported by Day 4 (−24.0% vs. −4.3% placebo, P = 0.012). In addition, there was a separation between groups in SD responders (decrease of ≥4 points) in favour of nemolizumab by Day 2 (8.8% vs. 0%, P = 0.037). Sleep continued improving through Week 4, when there was a −56.0% reduction in SD NRS vs. −22.9% placebo (P < 0.001). Actigraphy data showed improvement in scratch/sleep duration for nemolizumab vs. placebo, respectively, by Week 1 (−32.15 vs. +28.15 min/h, P = 0.001).