bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolated Minimally Invasive Mitral Valve Surgery in Octogenarians: Perioperative Outcome
Authors: Ntinopoulos Vasileios , Rodriguez Cetina Biefer Hector , Papadopoulos Nestoras , Dushaj Stak , Haeussler Achim , Dzemali Omer
Published: October 2023

Introduction: Despite the feasibility, safety, and excellent outcomes of mitral valve surgery through a right mini-thoracotomy, there is data paucity about its use in octogenarians. In this study, we assess the outcomes of mitral valve surgery via right mini-thoracotomy in octogenarians. Methods: We performed a retrospective analysis of the in-hospital perioperative data of 38 octogenarian patients with severe mitral regurgitation undergoing isolated mitral valve surgery via right mini-thoracotomy from 2013 to 2021 in our institution. Results: The median patient age was 82 (81–83) years, and the median EuroSCORE II was 3.1% (2.3–4.9). A total of 19 (50%) patients underwent mitral valve repair. The median cardiopulmonary bypass duration was 78 (54–100) min and the median aortic cross-clamping duration was 57 (40–70) min. Two (5.3%) patients were converted to sternotomy, 1 (2.6%) underwent renal replacement therapy, 5 (13.2%) underwent reexploration for bleeding or tamponade, and 12 (31.6%) underwent permanent pacemaker implantation. The surgical repair success rate was 89.5%, with 2 (10.5%) patients requiring reoperation due to repair failure. No other patients required reoperation on the mitral valve. The median intensive care unit stay was 1 (1–2) day, and the median postoperative stay was 9.5 (8–14) days. There was no perioperative stroke or death. Conclusion: Despite a relatively increased risk of pacemaker implantation and reexploration for bleeding, our data support the feasibility of mitral valve surgery via a right mini-thoracotomy in octogenarians, with short ischemic times, low overall in-hospital morbidity, and no mortality. Preferring replacement in mitral diseases with a high risk for repair failure could minimize reoperations in this high-risk subgroup.
Daily Affect and Daily Prospective Memory in People after Stroke and Their Partners: The Moderating Role of Resting Heart Rate
Authors: Luo Minxia , Pauly Theresa , Broen Tiana , Ashe Maureen C. , Murphy Rachel A. , Linden Wolfgang , Madden Kenneth M. , Gerstorf Denis , Hoppmann Christiane A.
Published: October 2023

Introduction: Experimental research suggests that affect may influence prospective memory performance, but real-life evidence on affect-prospective memory associations is limited. Moreover, most studies have examined the valence dimension of affect in understanding the influence of affect on cognitive performance in daily life, with insufficient consideration of the arousal dimension. To maximize ecological validity, the current study examined the relationships between daily affect and daily prospective memory using repeated daily assessments and the role of resting heart rate on these relationships. We examined both valence and arousal of daily affect by categorizing affect into four dimensions: high-arousal positive affect, low-arousal positive affect, high-arousal negative affect, and low-arousal negative affect. Method: We examined existing data collected from community-dwelling couples, of which at least one partner had a stroke history. The analytic sample included 111 adults (Mage = 67.46 years, SD = 9.64; 50% women) who provided 1,274 days of data. Among the participants, 58 were living with the effects of a stroke and 53 were partners. Participants completed daily event-based prospective memory tasks (in morning and/or evening questionnaires), reported daily affect in the evening, and wore a wrist-based Fitbit device to monitor resting heart rate over 14 consecutive days. Results: Results from multilevel models show that, within persons, elevated high-arousal negative affect was associated with worse daily prospective memory performance. In addition, lower resting heart rate attenuated the inverse association between high-arousal negative affect and lowered prospective memory performance. We did not find significant associations of high- or low-arousal positive affect and low-arousal negative affect with daily prospective memory. Discussion: Our findings are in line with the resource allocation model and the cue-utilization hypothesis in that high-arousal negative affect is detrimental to daily prospective memory performance. Lower resting heart rate may buffer individuals’ prospective memory performance from the influence of high-arousal negative affect. These findings are consistent with the neurovisceral integration model on heart-brain connections, highlighting the possibility that cardiovascular fitness may help maintain prospective memory into older adulthood.
N6-Methyladenosine Modifications in Pulmonary Hypertension
Authors: Xia Yu , Zhang Yanyan , Huang Jie , Chen Bing , Jiang YanJiao , Sun Zengxian , Liu Yun
Published: October 2023

Background: The most prevalent kind of RNA methylation modification existing in eukaryotes is N6-methyladenosine (m6A), which is a reversible type of posttranscriptional modification. Summary: Many studies have reported that m6A participates in cell differentiation, self-renewal, invasion, and apoptosis by modifying protein synthesis. Furthermore, m6A modification is also involved in disease progression and pulmonary vascular remodeling in pulmonary hypertension. However, very few researchers have investigated the effect of m6A modifications on pulmonary hypertension. Key Messages: Here, we have reviewed the latest research advances in the field of m6A RNA methylation in pulmonary hypertension and explored its regulatory role in pulmonary hypertension development and progression.
The Impact of Telemedicine during Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic and Future Perspectives: A Systematic Review
Authors: Monteleone Giorgio , Terzulli Giovanni , Cefaloni Francesca , Bonini Matteo , Richeldi Luca
Published: October 2023

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide since December 2019, causing the COVID-19 pandemic. Several measures have taken place in many countries to avoid further spread of the virus and to manage infected people according to disease severity. Notably, telemedicine (TM) was successfully used to manage less severe patients. Our aim was to assess the impact and the edges of using TM in home-isolated or hospitalized patients affected by SARS-CoV-2 infection and its further application. Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, focusing on randomized controlled trials (RCTs) published in English and available on PubMed database. Full texts were blindly reviewed and then assessed according to PICO model. Results: Our research identified a total of 1,959 records, of which 24 were potentially eligible through the articles full-text review. Six papers were included for data extraction and 18 articles were excluded: 10 articles were not RCTs and 8 articles did not involve SARS-CoV-2 patients. The TM application showed an improvement in psychological stress, mental disorders, and a significant reduction of general stress in patients affected by SARS-CoV-2 infection. The effectiveness of using TM in rehabilitative respiratory programs has been also reported. Furthermore, the benefits of TM application in tailored monitoring of vital parameters in home-isolated patients helped clinicians to early identify a deterioration of clinical conditions. Conclusion: The use of TM during COVID-19 pandemic represented a novel, intriguing, versatile, and useful tool to support clinical practice. This evidence suggests considering TM in a wider range of clinical applications.
Drug Allergy in Children: Adverse Reactions after Skin Testing
Authors: Karavaizoglu Cagla , Suleyman Ayse , Yavuz Alıc Roza , Dolu Kazım Okan , Yucel Esra , Demirkale Zeynep Hızlı , Cimen Sevgi Sipahi , Ozdemir Cevdet , Tamay Zeynep Ulker
Published: October 2023

Introduction: Skin tests are one of the most widely used diagnostic tools for suspected drug allergies in children. Studies on systemic reactions occurring during skin testing with allergens have mostly been conducted in pediatric and adult patient groups together. However, data on adverse reactions including allergic reactions after drug skin tests in children are scarce. It is aimed to determine the adverse reactions after skin test in children with suspected drug allergy. Methods: Patients who underwent a drug skin test due to the suspicion of drug allergy between May 2017 and June 2020 were evaluated, retrospectively. Data about adverse reactions seen after skin testing at the testing area in the clinic were analyzed. Results: The study included 1,073 children (585 [54.5%] boys and 488 [45.5%] girls) with a median age of 7.5 years. A total of 12 (1.1%) reactions were detected after skin testing, and 4 (0.4%) of them were allergic reactions. Of the allergic reactions, three were anaphylaxis and one was urticaria. Two of the reactions (1 anaphylaxis and 1 urticaria) were detected after the skin prick test and the remaining 2 were detected after intradermal test. Three of the nonallergic reactions were considered as vasovagal reactions and seven were considered as nonspecific and anxiety-related reactions. Conclusion: Although drug skin tests were generally well-tolerated and adverse reactions were rare, severe allergic reactions including anaphylaxis may ensue. Skin tests should be necessarily performed in clinical settings in experienced centers.
How Do Adherence to COVID-19 Mitigation Measures and Its Predictors Change between 2020 and 2021? An Explorative Investigation in Eight European Union and Non-European Union Countries
Authors: Brailovskaia Julia , Schneider Silvia , Zhang Xiao Chi , Margraf Jürgen
Published: October 2023

Introduction: Adherence to COVID-19 mitigation measures is an important vehicle that has contributed to the fight against the pandemic. The present study investigated potential changes of the level of adherence and its predictors between 2020 and 2021 in eight countries. Methods: Adherence to COVID-19 measures and its potential predictors (perception of usefulness of the measures, rating of the governmental COVID-19 communication, mental health variables, COVID-19 burden) were compared between representative population samples from European Union countries (France, Germany, Poland, Spain, Sweden) and non-European Union countries (Russia, UK, USA) assessed in 2020 (N = 7,658) and 2021 (N = 8,244). Results: In the overall sample, multiple analyses of variance revealed significantly higher levels of adherence to the measures, their perception as useful, positive mental health, and feelings of being well supported and well informed by governments in 2020 than in 2021. In contrast, feelings of being left alone and symptoms of depression, anxiety, and stress were significantly higher in 2021 than in 2020. In France, Poland, Spain, and the UK, the adherence level was significantly higher in 2020 than in 2021. In European Union countries, ratings of governmental communication were less positive, and levels of mental health were lower in 2021 than in 2020. In non-European countries, an opposite result pattern was found. Conclusion: The current results indicate a decrease in adherence to the mitigation measures and factors that could foster it. Potential ways how governments and authorities could enhance the population’s trust in COVID-19 mitigation measures are discussed.
DNA Methylation Pattern in Somatotroph Pituitary Neuroendocrine Tumors
Authors: Kober Paulina , Rymuza Julia , Baluszek Szymon , Maksymowicz Maria , Nyc Aleksandra , Mossakowska Beata J. , Zieliński Grzegorz , Kunicki Jacek , Bujko Mateusz
Published: October 2023

Introduction: Growth hormone secretion by sporadic somatotroph neuroendocrine pituitary tumors (PitNETs) is a major cause of acromegaly. These tumors are relatively heterogenous in terms of histopathological and molecular features. Our previous transcriptomic profiling of somatotroph tumors revealed three distinct molecular subtypes. This study aimed to investigate the difference in DNA methylation patterns in subtypes of somatotroph PitNETs and its role in distinctive gene expression. Methods: Genome-wide DNA methylation was investigated in 48 somatotroph PitNETs with EPIC microarrays. Gene expression was assessed with RNAseq. Bisulfite pyrosequencing and qRT-PCR were used for verifying the results of DNA methylation and gene expression. Results: Clustering tumor samples based on methylation data reflected the transcriptome-related classification. Subtype 1 tumors are densely granulated without GNAS mutation, characterized by high expression of NR5A1 (SF-1) and GIPR. The expression of both genes is correlated with specific methylation of the gene body and promoter. This subtype has a lower methylation level of 5′ gene regions and CpG islands than the remaining tumors. Subtype 2 PitNETs are densely granulated and frequently GNAS-mutated, while those in subtype 3 are mainly sparsely granulated. Methylation/expression analysis indicates that ∼50% genes located in differentially methylated regions are those differentially expressed between tumor subtypes. Correlation analysis revealed DNA methylation-controlled genes, including CDKN1B, CCND2, EBF3, CDH4, CDH12, MGMT, STAT5A, PLXND1, PTPRE, and MMP16, and genes encoding ion channels and semaphorins. Conclusion: DNA methylation profiling confirmed the existence of three molecular subtypes of somatotroph PitNETs. High expression of NR5A1 and GIPR in subtype 1 tumors is correlated with specific methylation of both genes.
The Influence of Pain on Reduced Quality of Life in Patients with Hidradenitis Suppurativa: A Single-Center Retrospective Study
Authors: Li Yiwen , Speck Patrick , Viera Eric , Siira Meron , Orenstein Lauren A.V.
Published: October 2023

Background: Pain and itch are impactful and burdensome symptoms of hidradenitis suppurativa (HS). Elucidating factors associated with pain and itch severity may identify groups disproportionally affected by HS-related pain and itch and further our understanding of how pain and itch impact quality of life (QoL) in patients with HS. Objective: The objective of the study was to determine factors associated with pain severity, itch severity, and reduced QoL in patients with HS. Methods: This is a retrospective cross-sectional study of 257 adults with HS who received care in an HS Specialty Clinic from January 2019 to August 2021. Multivariable mixed-effects linear regression was used to determine the relationships between clinical and demographic patient factors and the outcomes of pain severity, itch severity, and skin-specific QoL. Results: Factors associated with reduced QoL were Hurley stage II (β = 19.66, 95% CI: 1.40–37.93) and III (β = 21.98, 95% CI: 1.57–42.39) disease as well as severity of pain (β = 13.74, 95% CI: 11.93–15.55), itch (β = 4.57, 95% CI: 2.59–6.55), anxiety (β = 2.55 95% CI: 1.29–3.81), and depression (β = 1.43, 95% CI: 0.30–2.56). Increasing HS pain severity was associated with Hurley stage III disease (β = 2.04, 95% Cl: 0.99–3.09), black race (β = 1.23, 95% Cl: 0.40, 2.06), depression severity (β = 0.08, 95% Cl: 0.02, 0.14), and anxiety severity (β = 0.10 95% Cl: 0.04, 0.17). Factors associated with HS itch severity were Hurley stage III disease (β = 2.23, 95% Cl: 1.19, 3.27), black race (β = 0.92, 95% Cl: 0.07, 1.78), depression severity (β = 0.09, 95% Cl: 0.04, 0.14), and anxiety severity (β = 0.07, 95% Cl: 0.01, 0.13). Conclusion: Pain is one of the largest contributors to QoL in patients with HS; on a 0–10 numeric rating scale, a 2-point increase in HS pain had a similar independent effect on QoL as having Hurley stage III disease compared to Hurley stage I.
Weekend Effect on Clinical Outcomes of Acute Lower Gastrointestinal Bleeding: A Large Multicenter Cohort Study in Japan
Authors: Hayasaka Junnosuke , Kikuchi Daisuke , Ishii Naoki , Kobayashi Katsumasa , Yamauchi Atsushi , Yamada Atsuo , Omori Jun , Ikeya Takashi , Aoyama Taiki , Tominaga Naoyuki , Sato Yoshinori , Kishino Takaaki , Sawada Tsunaki , Murata Masaki , Takao Akinari , Mizukami Kazuhiro , Kinjo Ken , Fujimori Shunji , Uotani Takahiro , Fujita Minoru , Sato Hiroki , Suzuki Sho , Narasaka Toshiaki , Funabiki Tomohiro , Kinjo Yuzuru , Mizuki Akira , Kiyotoki Shu , Mikami Tatsuya , Gushima Ryosuke , Fujii Hiroyuki , Fuyuno Yuta , Gunji Naohiko , Toya Yosuke , Narimatsu Kazuyuki , Manabe Noriaki , Nagaike Koji , Kinjo Tetsu , Sumida Yorinobu , Funakoshi Sadahiro , Kobayashi Kiyonori , Matsuhashi Tamotsu , Komaki Yuga , Miki Kuniko , Watanabe Kazuhiro , Odagiri Hiroyuki , Hoteya Shu , Kaise Mitsuru , Nagata Naoyoshi
Published: October 2023

Introduction: Weekend admissions showed increased mortality in several medical conditions. This study aimed to examine the weekend effect on acute lower gastrointestinal bleeding (ALGIB) and its mortality and other outcomes. Methods: This retrospective cohort study (CODE BLUE-J Study) was conducted at 49 Japanese hospitals between January 2010 and December 2019. In total, 8,120 outpatients with acute hematochezia were enrolled and divided into weekend admissions and weekday admissions groups. Multiple imputation (MI) was used to handle missing values, followed by propensity score matching (PSM) to compare outcomes. The primary outcome was mortality; the secondary outcomes were rebleeding, length of stay (LOS), blood transfusion, thromboembolism, endoscopic treatment, the need for interventional radiology, and the need for surgery. Colonoscopy and computed tomography (CT) management were also evaluated. Results: Before PSM, there was no significant difference in mortality (1.3% vs. 0.9%, p = 0.133) between weekend and weekday admissions. After PSM with MI, 1,976 cases were matched for each admission. Mortality was not significantly different for weekend admissions compared with weekday admissions (odds ratio [OR] 1.437, 95% confidence interval [CI] 0.785–2.630; p = 0.340). No significant difference was found with other secondary outcomes in weekend admissions except for blood transfusion (OR 1.239, 95% CI 1.084–1.417; p = 0.006). Weekend admission had a negative effect on early colonoscopy (OR 0.536, 95% CI 0.471–0.609; p < 0.001). Meanwhile, urgent CT remained significantly higher in weekend admissions (OR 1.466, 95% CI 1.295–1.660; p < 0.001). Conclusion: Weekend admissions decrease early colonoscopy and increase urgent CT but do not affect mortality or other outcomes except transfusion.
Neoadjuvant Triplet Chemotherapy with Docetaxel, Cisplatin plus 5-Fluorouracil versus Docetaxel, Cisplatin plus S-1 for Advanced Esophageal Squamous cell Carcinoma: Propensity Score Matched Analysis
Authors: Kitadani Junya , Ojima Toshiyasu , Hayata Keiji , Goda Taro , Takeuchi Akihiro , Tominaga Shinta , Fukuda Naoki , Nakai Tomoki , Yamaue Hiroki , Kawai Manabu
Published: October 2023

Introduction: This study examines whether neoadjuvant docetaxel, cisplatin plus S-1 (DCS) therapy is superior to docetaxel, cisplatin plus 5-fluorouracil (DCF) therapy for resectable advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients diagnosed with resectable advanced ESCC at our hospital between January 2010 and December 2019 underwent either neoadjuvant DCF therapy or DCS therapy, followed by radical esophagectomy. Prior to August 2014, we usually used neoadjuvant DCF therapy; we then completely transitioned to using neoadjuvant DCS therapy. Results: A total of 144 patients received one of these triplet regimens as neoadjuvant chemotherapy: DCF therapy to 67 patients and DCS therapy to 77 patients. After propensity score matching, 55 patients in each group were selected as matched cohorts. There was no significant difference between the groups in complete response (DCF = 7.3%, DCS = 9.1%) or in partial response (DCF = 45.4%, DCS = 52.7%). The pathological response rate was 23.8% for grade 2 and 18.2% for grade 3 in the DCF group, compared with 30.9% and 14.5% in the DCS group. Independent predictive factors for recurrence-free survival were poor clinical response and pathological response ≤1b. Independent prognostic factors for overall survival were poor clinical response, anastomotic leakage, and pathological response ≤1b. Duration of hospital stays in the DCS group was significantly shorter than those of the DCF group (6.0 vs. 15.0 days, p < 0.001). Expenses of drug and hospitalization for the neoadjuvant chemotherapy in the DCS group were also significantly lower than those of the DCF group (265.7 vs. 550.3 USD, p < 0.001). Conclusions: Neoadjuvant DCS therapy for resectable advanced ESCC did not result in significantly higher clinical and pathological response than neoadjuvant DCF therapy. However, neoadjuvant DCS therapy for resectable ESCC required comparatively shorter hospital stays and incurred lower costs, making it an attractive therapeutic option.
Diagnostic Accuracy of Hyperpigmented Microcircles in Dermatoscopy of Non-Facial Non-Acral Melanomas: A Pilot Retrospective Study using a Public Image Database
Authors: Pietkiewicz Paweł , Giedziun Piotr , Idziak Jan , Todorovska Verce , Lewandowicz Michał , Lallas Aimilios
Published: October 2023

Background: Grey perifollicular circles are a dermatoscopic clue to melanoma, especially in facial skin. So far, no other adnexal clues than follicular have been investigated in this diagnosis. Objectives: The study aimed to analyse the prevalence of hyperpigmented periadnexal microcircles (HMs) in melanoma and its common simulators at non-facial non-acral sites, analyse the relation between the presence of HM, regression and hypopigmentation, and evaluate the diagnostic accuracy of this structure in melanoma. Methods: International Skin Imaging Collaboration (69,445 images) was searched in April 2020 for the pathology-confirmed dermatoscopic images with metadata including sex, age bin, and declared non-acral non-facial anatomic site. The final study sample (5,408 images, 1,326 of which were melanomas) was evaluated by expert dermatoscopist blinded to the diagnosis and labelled for the presence of ≥3 HM distributed centrally (cHM) or peripherally (pHM), hypopigmentation, and classic dermatoscopic regression structures. A subset of 40 images was labelled by 7 raters (2 residents, 5 experts) to assess interobserver agreement. We compared the presence of pHM with the presence of regression as well as performed a set of independent χ2 tests to evaluate the discriminatory power and its fragility. Performance of the models was assessed using measures of discrimination and calibration. Results: HM were significantly more prevalent in melanomas than in non-melanomas and nevi. Fair/good interobserver agreement for HM was reached for all the raters, and moderate/good for experts only (single rater/average, respectively). Regardless of regression/hypopigmentation status, pHM were significantly more common in melanoma than in non-melanomas or nevi and were observed significantly more often in melanomas on sun-damaged skin (upper extremity, posterior torso). No significant differences between the groups were found for cHM. pHM proved a high odds ratio in the tests as to the classical indicators such as classic dermatoscopic regression structures. Conclusion: pHM could be considered a novel dermatoscopic clue to melanoma.
Effects of Yoga Training Applied with Telerehabilitation on Core Stabilization and Physical Fitness in Junior Tennis Players: A Randomized Controlled Trial
Authors: Gergüz Çağla , Aras Bayram Gülay
Published: October 2023

Introduction: This study aimed to investigate the effects of yoga training applied with telerehabilitation on core stability, and strength, balance, flexibility, upper extremity stability, body awareness, and quality of life in tennis players aged 6–18 years. Methods: Forty tennis players were randomly divided into two groups to participate in this study. The control group (n = 20) continued tennis training and was informed about the importance of the core region. The yoga group (n = 20) received yoga training with telerehabilitation 2 days a week for 8 weeks. Athletes were evaluated with sport-specific core muscle strength and stability tests, the back scratch test, the sit and reach test, the flamingo balance test, the y-balance test (lower quarter), the upper extremity closed kinetic chain stability test, the SF-36, and body awareness questionnaires. Measurements have been done in the tennis club before and after the 8 weeks of training. Results: A significant increase was determined in core strength and stability, sit and reach, back scratch test, upper extremity stability, and body awareness questionnaire in the yoga group (p < 0.001). Flamingo and Y balance test results were significant (p < 0.002). Positive improvements were found in SF-36s energy-fatigue level, mental well-being, social function (p < 0.042), pain (p < 0.005), and general health (p < 0.001). A significant increase was observed in the core strength measurement mean score in the control group (p < 0.018). Sit and reach test, flamingo test, and body awareness questionnaire were found to be significant after the intervention (p < 0.001). Significant improvements were found in the pain (p < 0.042), and mental well-being (p < 0.001) sub-parameters of the SF-36. Conclusion: In the study, it was concluded that yoga training applied with telerehabilitation in tennis players aged 6–18 has a positive effect on core strength, and stabilization, physical fitness parameters, quality of life, and body awareness.
Homeopathic Treatment of Ramsay Hunt Syndrome: A Case Report
Authors: Bhakta Puja , Dutta Abhijit
Published: October 2023

Introduction: Ramsay Hunt syndrome (RHS) is an uncommon neurological complication resulting from the reactivation of latent herpes zoster virus. The condition often presents with facial paralysis, palatal ulcers, dysphagia, and altered taste sensation, leading to reduced quality of life. Standard therapeutic options for RHS have limitations, prompting the exploration of alternative treatments with improved prognostic outcomes. This case report aims to present a noteworthy clinical observation of RHS managed with individualized homeopathic treatment, emphasizing its potential therapeutic effect. Case Description: A 24-year-old female patient exhibited left-sided facial weakness, along with palatal ulcers, dysphagia, and ageusia, prompting the diagnosis of RHS. Following the principles of homeopathy, a personalized therapeutic regimen was formulated, consisting tailored administration of Rhus toxicodendron, Spigelia anthelmia, and Sulfur. The House-Brackmann scale was employed to objectively assess the severity of facial palsy, while photographic documentation tracked the progression of palatal ulcers and facial paralysis. Over a carefully monitored observation period of 14 days, the patient demonstrated notable therapeutic response. There was a significant reduction in the extent of palatal ulceration and left-sided facial palsy exhibited marked improvement. Subsequent days of follow-up witnessed a consistent amelioration of the patient’s condition, substantiating the effect of the individualized homeopathic treatment. Conclusion: This case report highlights an exceptional instance of RHS recovery within a relatively short timeframe, achieved through the administration of individualized homeopathic therapy. The favorable outcomes observed in this case underscore the potential of homeopathy as a promising intervention for RHS management. Nevertheless, further systematic investigations are imperative to comprehensively evaluate the scope and applicability of homeopathy in the treatment of RHS.
The Potential of Trastuzumab Deruxtecan as a Tissue Agnostic Drug
Authors: Jørgensen Jan Trøst
Published: October 2023

Background: Many modern anticancer drugs are designed to target specific molecular alterations harbored by the cancer. If a specific drug is able to target these alterations, regardless of the organ or tissue in which the cancer originates, it will often be characterized as a tissue- or tumor agnostic drug. According to the Food and Drug Administration (FDA), a tissue-agnostic drug refers to a drug that targets a specific molecular alteration across multiple cancer types, as defined by organ, tissue, or tumor type. Summary: Over the last 6 years, the FDA has approved seven tissue-agnostic drugs, and more are anticipated in the future. One promising candidate for a tissue-agnostic classification is the antibody-drug conjugate trastuzumab deruxtecan (T-DXd). Currently, T-DXd is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive and HER2-low breast cancer, HER2-positive gastric or gastroesophageal junction adenocarcinoma, and non-small cell lung cancer with activating HER2 mutations. Ongoing clinical research is exploring the potential of T-DXd in various solid tumors that harbor specific HER2 molecular alterations, and encouraging results, including the interim data from the DESTINY-PanTumor02 trial, have been published, which suggest a tissue-agnostic potential. Key Messages: Published phase I data as well as the interim results from the phase II DESTINY-PanTumor02 trial indicates that patients with different HER2-positive advanced solid tumors may benefit from treatment with T-DXd. Based on the currently available data, it seems likely that T-DXd possesses pantumor activity. However, different clinical trials are ongoing, and it will be necessary to see the results from these trials before drawing a final conclusion. When discussing tissue-agnostic potential, it is important to add that for most of the patients enrolled in the DESTINY-PanTumor02 and other trials, few treatment alternatives seem to exist, and T-DXd might be able to cover an unmet medical need.
Time of Delivery Contributes to Mortality and Morbidity in Preterm Infants
Authors: Teivaanmäki Tiina , Hallamaa Lotta , Rantakari Krista , Andersson Sture , Leskinen Markus
Published: October 2023

Introduction: Knowledge about the time of birth and its impact on premature infants is essential when planning perinatal and neonatal care and resource allocation. We studied the time of birth and its contribution to early death and morbidity in preterm infants. Methods: We explored the time and mode of birth of infants with birthweight of <1,500 g and gestational age of <32+0/7 weeks. Additionally, we divided the infants into three groups stratified by their time of birth, i.e., during office hours, evening, and nighttime and assessed associations between these groups and mortality and morbidity. Results: The study comprised 1,610 infants of whom 156 (10%) died during their stay in neonatal intensive care unit. The highest number of deliveries occurred on Fridays (21%, n = 341/1,610), primarily due to high number of cesarean sections. Deliveries peaked on workdays at 10 a.m. and 2:00 p.m. Mortality was lowest among infants born on Fridays (6%, n = 21/341) and highest on Mondays (13%, n = 28/218). Intraventricular hemorrhage (IVH) (odds ratio [OR]: 1.50, 95% CI: 1.10–2.03, p = 0.010) and necrotizing enterocolitis (NEC) (OR: 2.11, 95% CI: 1.13–3.91, p = 0.019) were more common among infants born at nighttime. These associations attenuated after adjustment for covariates. Conclusion: Deliveries of premature infants peaked on Fridays. Mortality was lower among those born on Fridays, compared with Mondays. Many low-risk deliveries on Fridays may decrease, and the tendency to postpone high-risk deliveries to Mondays, increase the proportional risk of mortality. Indication of higher risk of IVH and NEC among infants born during nighttime may be due to different patient population.
Identification of Fetuses at Increased Risk of Trisomies in the First Trimester Using Axial Planes
Authors: Montaguti Elisa , Diglio Josefina , Petrachi Benedetta , Arosio Viola , Fiorentini Marta , Cavalera Marta , Pellegrino Anita , Amodeo Silvia , Lenzi Jacopo , Pilu Gianluigi
Published: October 2023

Introduction: The measurement of nuchal translucency (NT) is crucial for assessing risk of aneuploidies in the first trimester. We investigate the ability of NT assessed by a transverse view of the fetal head to detect fetuses at increased risk of common aneuploidies at 11–13 weeks of gestation. Methods: We enrolled a nonconsecutive series of women who attended our outpatient clinic from January 2020 to April 2021 for aneuploidy screening by means of a first trimester combined test. All women were examined by operators certified by the Fetal Medicine Foundation. In each patient, NT measurements were obtained both from the median sagittal view and transverse view. We calculated the risk of aneuploidy using NT measurements obtained both with sagittal and axial scans, and then we compared the results. Results: A total of 1,023 women were enrolled. An excellent correlation was found between sagittal and transverse NT measurements. The sensitivity and specificity of the axial scan to identify fetuses that were deemed at risk of trisomy 21 using standard sagittal scans were 40/40 = 100.0% (95% confidence interval [CI]: 91.2–100.0) and 977/983 = 99.4% (95% CI: 98.7–99.7), respectively. The sensitivity and specificity of the axial scan to identify fetuses at risk of trisomy 13 or 18 were 16/16 = 100.0% (95% CI: 80.6–100.0) and 1,005/1,007 = 99.8% (95% CI: 99.3–99.9). Conclusions: When the sonogram, a part of combined test screening, is performed by an expert sonologist, axial views can reliably identify fetuses at increased risk of trisomies without an increase in false negative results.
Pushing Retinal Imaging Forward: Innovations and Their Clinical Meaning – The 2022 Ophthalmologica Lecture
Authors: Borrelli Enrico , Berni Alessandro , Mastropasqua Leonardo , Querques Giuseppe , Sadda Srinivas R. , Sarraf David , Bandello Francesco
Published: October 2023

Retinal imaging has greatly expanded our understanding of various pathological conditions. This article presents a summary of the key points covered during the 2022 Ophthalmologica Lecture held at the Euretina Congress in Hamburg. The first part of the article focuses on the use of optical coherence tomography angiography to examine and comprehend the choroid in age-related macular degeneration (AMD). Subsequently, we delve into the discussion of the “postreceptor neuronal loss” theory in AMD, which was studied using en face structural optical coherence tomography (OCT). Following that, we explore pertinent findings obtained through cross-sectional OCT in retinal and optic nerve diseases, such as AMD, diabetic macular edema, pathologic myopia, central serous chorioretinopathy, and Leber’s hereditary optic neuropathy.
Burgers, Fast Foods, and Increased Associated Risk for Atopic Dermatitis: A Cross-Sectional Study of Dietary Habits among Young Chinese Adults in Singapore/Malaysia
Authors: Lim Jun Jie , Lim Yi Ying Eliza , Ng Jun Yan , Malipeddi Praneeth , Ng Yu Ting , Teo Wei Yi , Wong Qi Yi Ambrose , Matta Sri Anusha , Sio Yang Yie , Wong Yi Ru , Teh Keng Foo , Rawanan Shah Smyrna Moti , Reginald Kavita , Say Yee-How , Liu Mei Hui , Chew Fook Tim
Published: October 2023

Background: We see increasing evidence that dietary and nutrients factors play a pivotal role in allergic diseases and recent global findings suggest that dietary habits influence the pathogenesis of atopic dermatitis (AD). Frequent consumption of fast food diets is associated with AD development. Despite the rising prevalence of AD in Asia, efforts in investigating the role of dietary habits and AD in adults are still lacking. Methods: We evaluated the association between the dietary intake of 16 food types and AD manifestations using our Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) population. Dietary habits profiles of 11,494 young Chinese adults (1,550 AD cases/2,978 non-atopic controls/6,386 atopic controls) were assessed by an investigator-administered questionnaire. AD cases were further evaluated for their chronicity (550 chronic) and severity (628 moderate-to-severe). Additionally, we derived a novel food index, Quality of Diet based on Glycaemic Index Score (QDGIS), to examine the association between dietary intake of glycaemic index (GI) and various AD phenotypes. Results: The majority of AD subjects are distributed in the good (37.1%) and moderate (36.2%) QDGIS classes. From the multivariable analyses for age and gender, a moderate QDGIS class was significantly associated with a lower odds of AD (adjusted odds ratio (AOR): 0.844; 95% confidence interval (CI): 0.719–0.991; p < 0.05) and moderate-to-severe AD (AOR: 0.839; 95% CI: 0.714–0.985; p < 0.05). A good QDGIS class was only significantly associated with a lower odds of chronic AD (AOR: 0.769; 95% CI: 0.606–0.976; p < 0.05). Among high GI foods, frequent consumption of burgers/fast food was strongly associated with an increased risk of chronic and moderate-to-severe AD. Among low GI foods, increased intake frequencies of fruits, vegetables, and pulses decreased the odds of AD. Finally, we identified significant associations between frequent seafood, margarine, butter, and pasta consumption with an increased odds of AD despite them having little GI values. Conclusion: While genetic components are well-established in their risks associated with increased AD prevalence, there is still a lack of a focus epidemiology study associating dietary influence with AD. Based on the first allergic epidemiology study conducted here in Singapore and Malaysia, it laid the groundwork to guide potential dietary interventions from changing personal dietary habits.
Fetal Thymus Size at 19–22 Weeks of Gestation: A Possible Marker for the Prediction of Low Birth Weight?
Authors: Kim Julia Maria , Oelmeier Kathrin , Braun Janina , Hammer Kerstin , Steinhard Johannes , Köster Helen Ann , Koch Raphael , Klockenbusch Walter , Schmitz Ralf , Möllers Mareike
Published: October 2023

Introduction: The purpose was to compare thymus size measured during second trimester screening of fetuses who were subsequently small for gestational age at birth (weight below 10th percentile, SGA group) with fetuses with normal birth weight (control group). We hypothesized that measuring the fetal thymic-thoracic ratio (TT-ratio) might help predict low birth weight. Methods: Using three-vessel view echocardiograms from our archives, we measured the anteroposterior thymus size and the intrathoracic mediastinal diameter to derive TT-ratios in the SGA (n = 105) and control groups (n = 533) between 19+0 and 21+6 weeks of gestation. We analyzed the association between TT-ratio and SGA adjusted to the week of gestation using logistic regression. Finally, we determined the possible TT-ratio cut-off point for discrimination between SGA and control groups by means of receiver operating characteristics (ROC) curve analysis. Results: The TT-ratio was significantly higher in the SGA group than in the control group (p < 0.001). An increase of the TT-ratio by 0.1 was associated with a 3.1-fold increase in the odds of diagnosing SGA. We determined that a possible discrimination cut-off point between SGA and healthy controls was achieved using a TT-ratio of 0.390 (area under the ROC curve 0.695). Conclusion: An increased TT-ratio may represent an additional prenatal screening parameter that improves the prediction of birth weight below the 10th percentile. Prospective studies are now needed to evaluate the use of fetal thymus size as predictive parameter for adverse fetal outcome.
Reframing Anorexia Nervosa: A Phenomenological Exploration of the Self-Other Relationship with Husserl’s Intersubjective Theory
Authors: Zhang Junguo
Published: October 2023

This paper explores the overlooked contributions of Husserl’s Phenomenology of intersubjectivity in understanding anorexia nervosa. It highlights the intricate relationship between the self and others, emphasizing their mutual constitution while acknowledging inherent differences. The distorted body image approach often overlooks this perspective, leading to psychopathological issues in individuals with anorexia nervosa. By integrating subjective experience and external observation, a more balanced and equal intersubjective relationship can be established. Utilizing this philosophical framework allows for a deeper understanding of the disorder’s dynamics and sheds new light on the subjective experiences of individuals with anorexia nervosa in relation to others.
Immunotherapy for Acute Myeloid Leukemia: Current Trends, Challenges, and Strategies
Authors: Chen Evan C. , Garcia Jacqueline S.
Published: October 2023

Background: In the past decade, there have been significant breakthroughs in immunotherapies for B-cell lymphoid malignancies and multiple myeloma, but progress has been much less for acute myeloid leukemia (AML). Nevertheless, challenge begets innovation and several therapeutic strategies are under investigation. Summary: In this review, we review the state of the art in AML immunotherapy including CD33- and CD123-targeted agents, immune checkpoint inhibition, and adoptive cell therapy strategies. We also share conceptual frameworks for approaching the growing catalog of investigational AML immunotherapies and propose future directions for the field. Key Messages: Immunotherapies for AML face significant challenges but novel strategies are in development.
Role of Pediatricians in Promoting and Supporting Breastfeeding: A Position Paper of the International Pediatric Association Strategic Advisory Group on Infant, Child, and Adolescent Nutrition
Authors: Fewtrell Mary , Bandsma Robert H. J. , Baur Louise , Duggan Christopher P. , Dumrongwongsiri Oraporn , Hojsak Iva , Khatami Katayoun , Koletzko Berthold , Kovalskys Irina , Li Zhenghong , Mouane Nezha , Nel Etienne , Sachdev Harshpal Singh , Spolidoro Jose Vicente
Published: October 2023

Background: Promoting and supporting breastfeeding is an important public health intervention with multiple benefits for both infants and mothers. Even modest increases in the prevalence and duration of breastfeeding could significantly reduce healthcare costs and improve maternal and child health outcomes. However, widespread adoption of breastfeeding recommendations remains poor in most settings, which contributes to widening health and social inequalities. Pediatricians have a duty to advocate for improving child health, including promoting and supporting breastfeeding. Summary: This paper, from the International Pediatric Association Special Advisory Group on Nutrition, considers common barriers to breastfeeding and addresses how pediatricians can better promote and support breastfeeding, both at an individual level and by influencing practice and policy. All pediatricians need to understand the basics of breastfeeding, including lactation physiology, recognize common breastfeeding problems, and advise mothers or refer them for appropriate support; training curricula for general pediatricians and all pediatric subspecialties should reflect this. Even in the situation where their day-to-day work does not involve direct contact with mothers and infants, pediatricians can have an important influence on policy and practice. They should support colleagues who work directly with mothers and infants, ensuring that systems and environments are conducive to breastfeeding and, where appropriate, milk expression. Pediatricians and pediatric organizations should also promote policies aimed at promoting and supporting breastfeeding at local, regional, national, and international levels. Key Messages: Pediatricians have a duty to promote and support breastfeeding, regardless of their day-to-day role and responsibilities. Pediatric training curricula should ensure that all trainees acquire a good understanding of breastfeeding so they are able to effectively support mothers in their personal practice but also influence breastfeeding practice and policy at a local, regional, national, and international level.
Revised Cut-Off Value of Human Epididymis Protein 4 Enhances Its Use as an Ovarian Tumor Marker
Authors: Machida Hiroki , Hirakawa Takashi , Tsunekawa Katsuhiko , Kimura Takao , Murakami Masami , Abe Yumiko
Published: October 2023

Objectives: Human epididymis protein 4 (HE4), a protein secreted by ovarian tumors, has been used as an ovarian tumor marker. This study aimed to improve the usefulness of HE4 to detect malignant ovarian tumors by reviewing the cut-off values. Design: A retrospective study without intervention was conducted. Participants: One hundred forty-nine healthy women (premenopausal, 126; postmenopausal, 23) and 24 patients with ovarian tumors (malignant, 12; benign, 12) participated in the study. Setting: The study used the Department of Obstetrics and Gynecology of a university hospital in Japan and the university hospital as a workplace from 2016 to 2018. Methods: The basic performance of the HE4 assay was evaluated, and the serum HE4 levels of participants were measured. Receiver operating characteristic analysis was performed using the HE4 data of the patients. Results: There were no significant differences in HE4 levels between the pre- and postmenopausal groups of healthy women. When the global cut-off values (premenopausal, 70 pmol/L; postmenopausal, 140 pmol/L) were adopted, the clinical sensitivity, specificity, positive predictive value, and negative predictive value were 41.7%, 91.7%, 83.3%, and 61.1%, respectively. Based on the results of the receiver operating characteristic analysis, we set the HE4 cut-off level at 60 pmol/L, regardless of the menopausal status. With the newly set cut-off value, the clinical sensitivity, specificity, positive predictive value, and negative predictive value were 66.7%, 91.7%, 88.9%, and 73.3%, respectively. That is, the clinical sensitivity of HE4 was improved without lowering specificity. Limitations: The small number of subjects and the fact that the health status of the healthy women was evaluated based on questionnaires were limitations to the study. Conclusion: A clinically useful cut-off value for HE4 as an ovarian tumor marker was established regardless of the menopausal status of the women, with improved clinical sensitivity, positive predictive value, and negative predictive value without lowering specificity. Currently, different cut-off values for HE4 in pre- and postmenopausal women are used globally. The cut-off value for CA125 was the same between pre- and postmenopausal women. Therefore, with the newly established cut-off value, HE4 can be used more conveniently in a non-specialized setting, especially when it is used in combination with CA125.
Radiomics Correlation to CD68+ Tumor-Associated Macrophages in Clear Cell Renal Cell Carcinoma
Authors: Shieh Alexander , Cen Steven Y. , Varghese Bino A. , Hwang Darryl , Lei Xiaomeng , Setayesh Ali , Siddiqi Imran , Aron Manju , Dsouza Anishka , Gill Inderbir S. , Wallace William , Duddalwar Vinay
Published: October 2023

Introduction: Renal cell carcinoma (RCC) is the ninth most common cancer worldwide, with clear cell RCC (ccRCC) being the most frequent histological subtype. The tumor immune microenvironment (TIME) of ccRCC is an important factor to guide treatment, but current assessments are tissue-based, which can be time-consuming and resource-intensive. In this study, we used radiomics extracted from clinically performed computed tomography (CT) as a noninvasive surrogate for CD68 tumor-associated macrophages (TAMs), a significant component of ccRCC TIME. Methods: TAM population was measured by CD68+/PanCK+ ratio and tumor-TAM clustering was measured by normalized K function calculated from multiplex immunofluorescence (mIF). A total of 1,076 regions on mIF slides from 78 patients were included. Radiomic features were extracted from multiphase CT of the ccRCC tumor. Statistical machine learning models, including random forest, Adaptive Boosting, and ElasticNet, were used to predict TAM population and tumor-TAM clustering. Results: The best models achieved an area under the ROC curve of 0.81 (95% CI: [0.69, 0.92]) for TAM population and 0.77 (95% CI: [0.66, 0.88]) for tumor-TAM clustering, respectively. Conclusion: Our study demonstrates the potential of using CT radiomics-derived imaging markers as a surrogate for assessment of TAM in ccRCC for real-time treatment response monitoring and patient selection for targeted therapies and immunotherapies.