bluuebunny/crossref_metadata_2025 huggingface dataset:
Duodenogastric Intussusception in a 14-Week-Old Infant with Donohue Syndrome: Case Study
Authors: Nicolescu Corina Ramona , Cremillieux Clara , Stephan Jean-Louis
Published: October 2023

Donohue syndrome (DS) is a rare recessively inherited disorder characterized by severe insulin resistance caused by genetic defects affecting the insulin receptor. The classical clinical characteristics include severe intrauterine growth restriction, craniofacial dysmorphic features, body and skin features, and soft tissue overgrowth. Postnatal growth retardation, cardiac, gastrointestinal, and renal complications, and infection susceptibility develop within the first few months of life, leading to a short life expectancy (<2 years). The classical metabolic abnormalities vary from fasting hypoglycemia to postprandial hyperglycemia with severe hyperinsulinemia. We present the case of a 14-week-old infant with DS who developed cardiac, renal, hepatic, pancreatic, and gastrointestinal features, all of them previously reported in infants with DS. The gastrointestinal features started during the first week of life and included abdominal distension, feeding difficulties, intermittent vomiting, and two episodes of intestinal obstruction. The diagnosis of duodenogastric intussusception was made, and this previously unreported complication tragically resulted in mortality. We discuss how basic mechanisms of cross-talk between insulin and insulin-growth factor 1 receptors could be linked to hyperinsulinemia and its associated comorbidities.
Using a Camera System for the In-Situ Assessment of Cordon Dieback due to Grapevine Trunk Diseases
Authors: Tang Julie , Yem Olivia , Russell Finn , Stewart Cameron A. , Lin Kangying , Jayakody Hiranya , Ayres Matthew R. , Sosnowski Mark R. , Whitty Mark , Petrie Paul R.
Published: October 2023

Background and Aims. The assessment of grapevine trunk disease symptoms is a labour-intensive process that requires experience and is prone to bias. Methods that support the easy and accurate monitoring of trunk diseases will aid management decisions. Methods and Results. An algorithm was developed for the assessment of dieback symptoms due to trunk disease which is applied on a smartphone mounted on a vehicle driven through the vineyard. Vine images and corresponding expert ground truth assessments (of over 13,000 vines) were collected and correlated over two seasons in Shiraz vineyards in the Clare Valley, Barossa, and McLaren Vale, South Australia. This dataset was used to train and verify YOLOv5 models to estimate the percentage dieback of cordons due to trunk diseases. The performance of the models was evaluated on the metrics of highest confidence, highest dieback score, and average dieback score across multiple detections. Eighty-four percent of vines in a test set derived from an unseen vineyard were assigned a score by the model within 10% of the score given by experts in the vineyard. Conclusions. The computer vision algorithms were implemented within the phone, allowing real-time assessment and row-level mapping with nothing more than a high-end mobile phone. Significance of the Study. The algorithms form the basis of a system that will allow growers to scan their vineyards easily and regularly to monitor dieback due to grapevine trunk disease and will facilitate corrective interventions.
A Comparative Study of Particle Swarm Optimization and Artificial Bee Colony Algorithm for Numerical Analysis of Fisher’s Equation
Authors: Arora Geeta , Bala Kiran , Emadifar Homan , Khademi Masoumeh
Published: October 2023

The aim of this research work is to obtain the numerical solution of Fisher’s equation using the radial basis function (RBF) with pseudospectral method (RBF-PS). The two optimization techniques, namely, particle swarm optimization (PSO) and artificial bee colony (ABC), have been compared for the numerical results in terms of errors, which are employed to find the shape parameter of the RBF. Two problems of Fisher’s equation are presented to test the accuracy of the method, and the obtained numerical results are compared to verify the effectiveness of this novel approach. The calculation of the error norms leads to the conclusion that the performance of PSO is better than the ABC algorithm to minimize the error for the shape parameter in a given range.
KRT17high/CXCL8+ Tumor Cells Display Both Classical and Basal Features and Regulate Myeloid Infiltration in the Pancreatic Cancer Microenvironment
Authors: Carpenter Eileen S. , Kadiyala Padma , Elhossiny Ahmed M. , Kemp Samantha B. , Li Jay , Steele Nina G. , Nicolle Rémy , Nwosu Zeribe C. , Freeman Julia , Dai Henry , Paglia Daniel , Du Wenting , Donahue Katelyn , Morales Jacqueline , Medina-Cabrera Paola I. , Bonilla Monica E. , Harris Lindsey , The Stephanie , Gunchick Valerie , Peterson Nicole , Brown Kristee , Mattea Michael , Espinoza Carlos E. , McGue Jake , Kabala Sarah M. , Baliira Rachel K. , Renollet Nur M. , Mooney Ayden G. , Liu Jianhua , Bhalla Sean , Farida Jeremy P. , Ko Christopher , Machicado Jorge D. , Kwon Richard S. , Wamsteker Erik-Jan , Schulman Allison , Anderson Michelle A. , Law Ryan , Prabhu Anoop , Coulombe Pierre A. , Rao Arvind , Frankel Timothy L. , Bednar Filip , Shi Jiaqi , Sahai Vaibhav , Pasca Di Magliano Marina
Published: October 2023

Purpose:

Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single-cell RNA sequencing has uncovered the coexistence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach.

Experimental Design:

We performed subtyping on a single-cell RNA sequencing dataset containing 18 human PDAC samples to identify multiple intermediary subtypes. We generated patient-derived PDAC organoids for functional studies. We compared single-cell profiling of matched blood and tumor samples to measure changes in the local and systemic immune microenvironment. We then leveraged longitudinally patient-matched blood to follow individual patients over the course of chemotherapy.

Results:

We identified a cluster of KRT17-high intermediary cancer cells that uniquely express high levels of CXCL8 and other cytokines. The proportion of KRT17high/CXCL8+ cells in patient tumors correlated with intratumoral myeloid abundance, and, interestingly, high protumor peripheral blood granulocytes, implicating local and systemic roles. Patient-derived organoids maintained KRT17high/CXCL8+ cells and induced myeloid cell migration in a CXCL8-dependent manner. In our longitudinal studies, plasma CXCL8 decreased following chemotherapy in responsive patients, while CXCL8 persistence portended worse prognosis.

Conclusions:

Through single-cell analysis of PDAC samples, we identified KRT17high/CXCL8+ cancer cells as an intermediary subtype, marked by a unique cytokine profile and capable of influencing myeloid cells in the tumor microenvironment and systemically. The abundance of this cell population should be considered for patient stratification in precision immunotherapy.

See related commentary by Faraoni and McAllister, p. 2297
TABLE 4 from Immune-related Adverse Events after Immune Checkpoint Blockade–based Therapy Are Associated with Improved Survival in Advanced Sarcomas
Authors: Rosenbaum Evan , Seier Kenneth , Bradic Martina , Kelly Ciara , Movva Sujana , Nacev Benjamin A. , Gounder Mrinal M. , Keohan Mary L. , Avutu Viswatej , Chi Ping , Thornton Katherine A. , Chan Jason E. , Dickson Mark A. , Donoghue Mark T.A. , Tap William D. , Qin Li-Xuan , D'Angelo Sandra P.
Published: October 2023

Association between immune cell proportions in patients with and without irAE
Bacillary Layer Detachment in Diabetic Retinopathy: A Case Report
Authors: Amini Abdulrahim , Riazi-Esfahani Hamid , Cheraqpour Kasra , Johari Mohammadkarim , Bolkheir Alireza , Mahdizad Zahra , Ghassemi Fariba
Published: October 2023

To our knowledge, this is the first report to describe bacillary layer detachment (BLD) in a patient with diabetic retinopathy treated with anti-vascular endothelial growth factor. We present the case of a 55-year-old diabetic female who was referred to our hospital complaining of decreased vision in her left eye for 2 weeks. Fundus examination of both eyes was compatible with diabetic retinopathy. Spectral-domain optical coherence tomography of the left eye showed a large dome-shaped cystic space with marginal septa, splitting the myoid zone, consistent with the BLD phenotype. A single dose of intravitreal bevacizumab injection was administered. After 4 weeks, BCVA was improved significantly with complete resolution of BLD. Underlying choroidal ischemia in patients with different vascular disorders like diabetes mellitus may lead to photoreceptor stress and BLD. This study adds to the growing literature, which describes BLD as a marker of fluid accumulation in relation to several macular diseases.
Pigmented Nevus of the Caruncle and Plica Semilunaris: A Case Report
Authors: Meyerov Joshua , Levitz Lewis , Haddad Afaf
Published: October 2023

Conjunctival nevi are benign, heterogenous tumors that uncommonly arise from the lacrimal caruncle and plica semilunaris. We present a case of a patient diagnosed and managed for an unusual, pigmented nevus of the left caruncle involving the plica. An 84-year-old woman presented with a rapidly growing, pigmented lesion in her left nasal canthus. Examination demonstrated a raised, dark, pigmented area arising from the left caruncle and seeming to involve the plica semilunaris without scleral extension. The lesion was completely excised for histopathology, which confirmed the diagnosis of a compound nevus with pigment incontinence. Given the unfavorable anatomical position and prognostic significance in the case of malignancy, pigmented caruncular lesions should be thoroughly investigated with a low threshold for surgical removal.
Orbital Perivascular Epithelioid Cell Tumor in a Case of Tuberous Sclerosis
Authors: Aljneibi Shaikha H , Aldhanhani Aisha A , Abuhaleeqa Khaled , Pichi Francesco
Published: October 2023

The aim of the study was to report a case of orbital perivascular epithelioid cell tumor (PEComa) in a known diagnosed patient of tuberous sclerosis and retinal astrocytic hamartoma. 43-year-old female presented with rapid progressive painful proptosis in the left eye, also reported new mass growing in her upper back. The patient past medical history is significant for left renal angiomyolipoma and multiple bilateral lung cysts of which she underwent right nephrectomy and lung biopsy, respectively. The lung biopsy turned diagnostic for lymphangiomyomatosis. On external examination, the left eye was grossly proptotic with hypoglobus. A typical butterfly distribution of sebaceous adenoma was noted across the patient cheeks and nose. Visual acuity in the right eye was 20/20 and the left eye, 20/25. Funduscopic examination identified type 1, 2, and 3 retinal astrocytic hamartomas. MRI brain and orbit was significant for a lesion arising from the lateral orbital wall with extensive bone destruction, displacing the left optic nerve medially. CT chest showed left extrathoracic mass had same radiological features as the orbital lesion; thus, an incisional biopsy performed on the former was diagnostic for PEComa with atypical features. This is the first observed case of PEComa in a known diagnosed patent with TS and retinal astrocytic hamartoma. The association of tuberous sclerosis complex and orbital PEComa is rarely and poorly reported in the literature compared to extraocular PEComa.
Long-Read Sequencing in Blood Group Genetics
Authors: Thun Gian Andri , Gueuning Morgan , Mattle-Greminger Maja
Published: October 2023

Background: The key advantages of latest third-generation long-read sequencing (TGS) technologies include the ability to resolve long haplotypes and to characterize genomic regions that are challenging to analyze with short-read sequencing. Recent advancements in TGS technologies have significantly improved accuracy, a crucial requirement for the transition from research to diagnostic applications. Summary: In the field of immunohematology, the adoption of TGS is still in its early stages and published applications are scarce. An undeniable utility of TGS in blood group genomics is the ability to resolve ambiguous genotype-phenotype blood group results. In particular, hybrid genes and other large structural variants, as commonly found in the RHD/CE and MNS blood group systems, cause such discrepant results that can hardly be resolved by conventional methods. Long-read sequencing also greatly aids to generate high-standard reference alleles, establish haplotype sequence databases, or could even serve for high-resolution genotyping of all blood groups in parallel. Additionally, TGS holds the potential to close important knowledge gaps in blood group transcriptomics and epigenetics. Key Messages: The aims of this review were to examine the prospects of TGS technologies within the field of immunohematology and to highlight practical applications. Furthermore, we present a comprehensive overview of the existing and emerging wet-laboratory strategies for data generation, as well as a summary on bioinformatic data analysis methods. Finally, we provide an outlook on anticipated advancements in the near future.
Infestation of the Eyelid by an Egg-Laying Tick: Case Report
Authors: Hakami Sina , Afifi Youssef , Azzagnuni Younes , Makhoul Dorine , Le Aurelie
Published: October 2023

In this report, we describe a rare case of a tick egg-laying infestation of the eyelid. A 7-year-old girl consulted our hospital after a trip in Thailand for an itchy and painful eyelid. The first examination at the slit lamp showed the tick’s body attached to the left superior eyelid margin, surrounded by its eggs. The tick detached itself afterward and a tobramycin prophylactic treatment was introduced. The patient was put under surveillance and no signs of a tick-borne disease were described during the follow-up.
A Case of Bilateral Frosted Branch Angiitis after mRNA COVID-19 Vaccination
Authors: Kitaoka Mai , Ohnishi Takako , Sugaya Satoshi , Yokota Harumasa , Nagaoka Taiji , Yamagami Satoru
Published: October 2023

We report a case of bilateral frosted branch angiitis (FBA) following mRNA-1273 COVID-19 vaccination. A 79-year-old male was referred to our hospital with a sudden onset of blurred vision in the right eye, which occurred during his return home after receiving the third dose of a messenger RNA (mRNA) COVID-19 vaccine. Fundoscopy revealed severe retinal vasculitis with sheathing of the artery and vein in the right eye more so than in the left eye, suggestive of bilateral FBA. Optical coherence tomography showed significant macular edema and serous retinal detachment in the right eye. Polymerase chain reaction assay detected Epstein-Barr virus (EBV) in the aqueous humor, and antibody against the EBV viral capsid antigen was positive for IgM. The next day, best-corrected visual acuity (BCVA) worsened to 0.08 due to macular edema in the left eye. After 2 courses of pulse steroid therapy and intravenous infusion of acyclovir, macular edema had disappeared and sheathing of retinal vessels was improving. At 5 months after the mRNA COVID-19 vaccination, BCVA was maintained 0.15 in the right eye and 0.7 in the left eye. Severe uveitis, such as FBA, can occur after mRNA COVID-19 vaccination.
A Case of Autism Spectrum Disorder with Perforated Keratomalacia due to Vitamin A Deficiency
Authors: Nakata Daisuke , Kakehi Sayaka , Okada Hiroshi , Hirano Koji , Horiguchi Masayuki , Ito Yasuki
Published: October 2023

We report a case of a patient with autism spectrum disorder (ASD) and perforated keratomalacia secondary to vitamin A deficiency. A 6-year-old boy complained of difficulty in opening the eyelids. The ocular conjunctiva was hyperemic and keratinized with purulent ocular (eye) discharge. Both corneas showed epithelial defects with hypopyon. The serum vitamin A level was ≤5 IU/dL (normal 97–316), leading to a diagnosis of xerophthalmia and keratomalacia due to vitamin A deficiency. Intramuscular injection of vitamin A (50,000 IU/day), as well as oral administration of multivitamin (containing 2,500 IU of vitamin A) and zinc supplement at 50 mg/day, allowed him to open both eyes and show interest in tablet devices 14 days after the diagnosis. During the course of the treatment, corneal perforation was observed, but it was closed without contact lens wear or amniotic patch and managed with vitamin A replacement therapy and antimicrobial eye drops. The epithelium extended to the area of the right cornea that had been melted, and although scarring corneal opacity remained, there were no obvious signs of infection. Early diagnosis is difficult because children with ASD do not express complaints, and vitamin A deficiency should be considered in patients with a severely unbalanced diet and complaints of difficulty opening the eyelids.
Reticular Pseudodrusen Voids after Rhegmatogenous Retinal Detachment
Authors: Forsaa Vegard Asgeir , Thomseth Vilde Marie
Published: October 2023

We present a case of reticular pseudodrusen (RPD) regression on multimodal retinal imaging following a rhegmatogenous retinal detachment. Two mechanisms of action can be postulated. The subretinal deposits dissolve due to voluminous subretinal fluid during retinal separation from the retinal pigment epithelium and are in turn mechanically cleared during retinal re-attachment surgery. Alternatively, an RPD clearance is facilitated by enhanced phagocytic activity of macrophages and microglial cells as a response to acute retinal stress.
Bilateral Optic Disc Swelling with Persistent Visual Loss in Anemia: Case Report
Authors: Van Langenhove Kim , Ten Tusscher Marcel Paulus Maria
Published: October 2023

A 56-year-old man with a medical history of alcoholic cirrhosis presented with acute bilateral loss of vision. On admission, the patient had pale skin and low arterial pressure. Ophthalmic examination demonstrated a visual acuity of 6/9 in the right eye and the absence of light perception in the left. Automated perimetry revealed a superior altitudinal defect in the right eye. Optic disc swelling, flame-shaped hemorrhages, and several cotton-wool spots were evident in both eyes on fundoscopy. Lab results confirmed severe anemia. Following prompt correction of the anemia, the altitudinal defect remained unchanged. However, visual acuity in the right eye improved significantly in a few days. The potential association of anemia with both papilledema and non-arteritic anterior ischemic optic neuropathy (NA-AION) is discussed, with a focus on possible pathophysiological mechanisms. The necessity for routine anemia screening, encompassing complete blood count, serum iron, and vitamin B12 levels, and subsequent rapid correction in these patients, is emphasized.
Risk Factors for Neurodevelopmental Impairment at 2- and 5-Years Corrected Age in Preterm Infants with Established Bronchopulmonary Dysplasia
Authors: Katz Trixie A. , van Kaam Anton H. , Mugie Suzanne M. , Aarnoudse-Moens Cornelieke S.H. , de Groof Femke , van Kempen Anne A.M.W. , van den Heuvel Maria E. N , Vogelzang Judith , Rijpert Maarten , Schiering Irene A. , Koomen-Botman Irene , Visser Fenna , Leemhuis Aleid G. , Onland Wes
Published: October 2023

Introduction: The objective of this study was to identify risk factors for neurodevelopmental impairment (NDI) at 2- and 5-years corrected age (CA) in a cohort of preterm infants with established bronchopulmonary dysplasia (BPD). Methods: This single-center retrospective cohort study included infants born between 2009 and 2016 at a gestational age (GA) <30 weeks with moderate or severe BPD at 36 weeks’ postmenstrual age. Perinatal characteristics, (social) demographics, and comorbidities were collected from the electronic patient records. Odds ratios for NDI were calculated with univariate and multivariate logistic regression analyses adjusting for potential confounders. Results: Of the 602 eligible infants, 123 infants were diagnosed with BPD. NDI was present in 30.3% and 56.1% at 2- and 5-years CA, respectively. The only independent risk factors associated with NDI in the multivariate analyses were birthweight (adjusted odds ratio [aOR] 0.74, 95% CI 0.57–0.95; aOR 0.70, 95% CI 0.54–0.91, respectively), small for GA (SGA) (aOR 3.25, 95% CI 1.09–9.61; aOR 5.44, 95% CI 1.62–18.2, respectively) at both time points, and male gender at 5-years CA (OR 2.49, 95% CI 1.11–5.57). Conclusion: Birthweight and SGA are independent risk factors for NDI at 2- and 5-years CA and male gender at 5-years CA in preterm infants with BPD. In contrast, well-known other risk factors for NDI in the general population of preterm infants, such as GA, maternal education, and neonatal comorbidities were not independently associated with NDI.
Autism as a Disorder of Affective Empathy
Authors: Schnitzler Tim , Fuchs Thomas
Published: October 2023

Since the first description by Leo Kanner, individuals with autism spectrum disorder (ASD) have been attributed a reduced empathy. However, it has not yet been clarified how empathy is specifically impaired in autism. Typically, scholars distinguish between the affective and the cognitive dimensions of empathy. The latter largely overlaps with the concept of the theory of mind (ToM), according to which we need internal inferences or simulations for gaining access to the hidden mental states of others. Since a deficit in ToM is a widely accepted explanation for difficulties of individuals with ASD in social interactions, limitations in cognitive empathy are accordingly assumed. Regarding affective empathy, there are contradictory results using various methods, showing an impaired affective empathy. The main aim of the paper is to present ASD primarily as a disorder of shared interpersonal and interaffective experiences and thus of affective empathy by means of a phenomenological analysis considering empirical studies. In this framework, a deficit of the ToM is accepted but criticized as a central explanatory approach for ASD since (1) it assumes a fundamental inaccessibility of other people, which does not correspond to our everyday social situations, and (2) it manifests developmentally long after the first signs of ASD, which means that its deficit cannot explain the basic autistic difficulties in social interactions.
Decreased Basophil Activation against House Dust Mite after Japanese Cedar Pollen Subcutaneous Immunotherapy: A Retrospective Study
Authors: Inuo Chisato , Ando Hitoshi , Tanaka Kenichi , Nakajima Yoichi , Tsuge Ikuya , Urisu Atsuo , Kondo Yasuto
Published: October 2023

Background: Allergen-specific immunotherapy (AIT), an established treatment for allergic diseases, prevents the development of other allergic manifestations. Although the mechanisms remain unclear, AIT has been shown to reduce basophil activation (BA) against nontarget allergens. Objectives: The aim of this study was to assess immunological changes in Dermatophagoides farinae (Der f) after Japanese cedar pollen (JCP)-based subcutaneous immunotherapy (SCIT) monotherapy. Method: The data of 16 patients (age: 6–37 years) with JCP-induced allergic rhinitis who were sensitive to Der f (serum Der f-specific immunoglobulin E [IgE] level >0.34 kUA/L) and received JCP-based SCIT for 5 years were reviewed retrospectively. BA by Der f and JCP extracts and serum-specific IgE and immunoglobulin G4 (IgG4) levels against these allergens were evaluated before and after completing 5 years of JCP-based SCIT monotherapy. Results: The areas under the dose-response curves of BA by Der f and JCP extracts were significantly reduced (p = 0.02 and p = 0.002, respectively). JCP-specific IgE levels decreased and JCP-specific IgG4 levels increased significantly (p < 0.001 for both), whereas Der f-specific IgE and IgG4 levels did not change significantly. Conclusions: JCP-based SCIT monotherapy reduced Der f-specific BA. These findings suggest that JCP-based SCIT has the potential to modulate immune response toward nontarget allergens.
A Case of Nocardia africana-Related Keratitis
Authors: Chaidaroon Winai , Sawetwong Prangchanok , Manochomphu Sirinya
Published: October 2023

Nocardia spp. are gram positive, aerobic, weakly acid-fast bacteria. Nocardia spp. keratitis is a rare ocular infection classically described following corneal injury or vegetative and soil exposure. However, keratitis caused by Nocardia africana had never been reported in the literature. We first reported a 70-year-old male who had a traumatic ocular injury to his left eye a month ago. With his complaint of left eye pain, reduced vision, and light sensitivity, the slit-lamp biomicroscopy showed the superficial multi-lobulated epithelial infiltration located at the inferior cornea with a positive fluorescein stain. Microscopic workup from corneal specimens demonstrated dry and chalky white colonies on blood agar and Lowenstein-Jensen media resembling Nocardia spp. The MALDI-TOF MS analyses using VITEK® MS exhibited N. africana. The corneal lesion was treated with 2% amikacin topical eye drops and responded well. The careful history-taking, precise clinical examinations, and meticulous microscopic assessment were the cornerstones of diagnosis. Definite diagnosis and timely treatment were essential to prevention of ocular morbidity in N. africana.
The Treatment of Coronary Artery Disease in Patients with Chronic Kidney Disease: Gaps, Challenges, and Solutions
Authors: Losin Ilya , Hagai Keren-Cohen , Pereg David
Published: October 2023

Background: Chronic kidney disease (CKD) is associated with a high burden of coronary artery disease (CAD), which remains the leading cause of death in CKD patients. Despite the high cardiovascular risk, ACS patients with renal dysfunction are less commonly treated with guideline-based medical therapy and are less frequently referred for coronary revascularization. Summary: The management of CAD is more challenging in patients with CKD than in the general population due to concerns regarding side effects and renal toxicity, as well as uncertainty regarding clinical benefit of guideline-based medical therapy and interventions. Patients with advanced CKD and especially those receiving dialysis have not traditionally been represented in randomized trials evaluating either medical or revascularization therapies. Thus, only scant data from small prospective studies or retrospective analyses are available. Recently published studies suggest that there are significant opportunities to substantially improve both cardiovascular and renal outcomes of patients with CAD and CKD, including new medications and interventions. Thus, the objective of this review is to summarize the current evidence regarding the management of CAD in CKD patients, in particular with respect to improvement of both cardiovascular and renal outcomes. Key Messages: Adequate medical therapy and coronary interventions using evidence-based strategies can improve both cardiac and renal outcomes in patients with CAD and CKD.
Severe Corneal Melt Post Trans-Scleral Cyclodiode in a Case of Neovascular Glaucoma Secondary to Coats Disease: A Case Report
Authors: Lee Jackson Chee Chea , Chan Geoffrey Zhi Peng , Shahid Humma
Published: October 2023

A novel case of neurotrophic keratitis and severe corneal melt requiring surgical management is presented 1 month following trans-scleral cyclodiode for Coats disease and neovascular glaucoma. Risk factors contributing to the complication include previous extracapsular cataract surgery, perioperative use of topical non-steroidal anti-inflammatories and dexamethasone/neomycin, as well as other topical drops containing preservatives such as benzalkonium chloride. Meticulous consideration of preoptimization of the ocular surface and rationalization of perioperative eye drop regimes is discussed.
Causes and Risk Factors for Absenteeism among Medical Staff in German Specialized Lung Clinics during the COVID Pandemic
Authors: Piel Stella , Presotto Maria A. , Jörres Rudolf A. , Karrasch Stefan , Gesierich Wolfgang , Bullwinkel Jörn , Rabe Klaus F. , Hayden Markus C. , Kaestner Franziska , Harzheim Dominik , Joves Biljana , Kempa Axel T. , Ghiani Alessandro , Neurohr Claus , Michels Julia D. , Kreuter Michael , Herth Felix J.F. , Trudzinski Franziska C.
Published: October 2023

Background: Staff shortages pose a major challenge to the health system. Objectives: The objective of this study was to clarify the role of different causative factors we investigated on staff absenteeism during the COVID pandemic. Methods: The prospective multicentre cohort study assessed the private and professional impact of the pandemic on health care workers (HCWs) using a specially developed questionnaire. HCWs from 7 specialist lung clinics throughout Germany were surveyed from December 1 to December 23, 2021. The current analysis addresses pandemic-related absenteeism. Results: 1,134 HCW (55% female; 18.4% male, 26.3% not willing to provide information on age or gender) participated. 72.8% had received at least one vaccination dose at the time of the survey, and 9.4% reported a COVID infection. Of those with positive tests, 98% reported home quarantine for median (IQR) 14 (12–17) days; 10.3% of those who ultimately tested negative also reported quarantine periods of 14 (7–14) days. 32.2% of vaccinated respondents reported absenteeism due to vaccine reactions of 2 (1–3) days. Overall, 37% (n = 420) of HCW reported pandemic-related absenteeism, with 3,524 total days of absenteeism, of which 2,828 were due to illness/quarantine and 696 to vaccination effects. Independent risk factors for COVID-related absenteeism ≥5 days included already having COVID, but also concern about long-term effects of COVID (OR 1,782, p = 0.014); risk factors for vaccine-related absenteeism ≥2 days included concerns of late effects of vaccination (OR 2.2, 95% CI: 1.4–3.1, p < 0.000). Conclusion: Staff shortages due to quarantine or infections and vaccine reactogenicity have put a strain on German respiratory specialists. The fact that staff concerns also contributed to absenteeism may be helpful in managing future pandemic events to minimize staff absenteeism.
A Systematic Review and Bayesian Network Meta-Analysis of Medical Therapies for Lichen Planopilaris
Authors: Husein-ElAhmed Husein , Husein-ElAhmed Sara
Published: October 2023

Background: Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia. Unfortunately, current available treatments are not fully effective to stop hair loss, and the level of evidence for medical interventions is weak. Objectives: The present article aimed to determine the efficacy of the different medical interventions in LPP through a network meta-analysis (NMA). Methods: A systematic review and meta-analysis were performed including randomized trials that report the outcomes of lichen planopilaris activity index (LPPAI). These articles were pooled and a NMA was conducted. Results: A total of seven studies were identified and included in meta-analysis, comprising 251 LPP patients. The NMA showed the mean difference in LLPAI was significantly superior with the combination of clobetasol plus N-acetylcysteine (mean difference: −2.0, 95% CI = −3.43 to −0.51) and the combination of clobetasol plus pentoxifylline (mean difference: −1.62, 95% CI = −3.0 to −0.25) compared to the treatment of reference (clobetasol). The NMA showed cyclosporine (mean difference: 2.05 95% CI = 0.68–3.49), methotrexate (mean difference: 1.95 95% CI = 1.23–3.17), the combination of methotrexate plus prednisolone (mean difference: 1.56 95% CI = 0.25–2.96) were significantly worse than hydroxychloroquine according to the differences in LLPAI. Conclusion: This work is the first NMA in LPP and hence, it can be helpful in serving as an initial step toward better evidence-based decisions in the treatment of this challenging condition. We propose a triple-combined approach consisting of topical clobetasol, hydroxychloroquine, and N-acetylcysteine as resulted in the most effective approach. Considering the poor outcomes observed with pioglitazone, mycophenolate mofetil, and cyclosporine, it is advisable to contemplate the use of these medications in patients who have not responded adequately to more efficacious alternatives.
Acupuncture and Traditional Chinese Medicine in the Treatment of Peripheral Facial Palsy Caused by Wisdom Tooth Extraction: A Case Report
Authors: Li Dong , Tao Larissa , Wei Xifang , Cai Wa , Shen Weidong
Published: October 2023

Background: Peripheral facial palsy is characterized by acute peripheral facial nerve paralysis. While most cases have no identifiable cause, some are linked to infectious or noninfectious factors. The potential connection between herpes simplex virus-1 and peripheral facial palsy has been studied since the 1970s, with a small number of cases reported following tooth extraction. Patients who have treatment delayed for over a year and still exhibit no signs of recovery have a bleak prognosis. In this case, factors contributing to facial paralysis in this patient are facial nerve injury as a result of wisdom teeth extraction, improper nursing, and delayed treatment. Case Presentation: A 23-year-old female presented with numbness and stiffness on the right side of the outer skin around the lips. These symptoms persisted for about 4 years after the extraction of the right lower wisdom tooth. Physical examination revealed House-Brackmann grade II peripheral facial paralysis. Acupuncture and traditional Chinese medicine treatments were initiated with an aim to facilitate nerve repair and neurofacilitation in the affected area. Following a 4-week course of treatment, the patient experienced a decrease in numbness and stiffness in the area, and treatment was discontinued. Conclusion: The combination of acupuncture and traditional Chinese medicine is a safe and promising supplementary therapy for peripheral facial palsy caused by wisdom tooth extraction. Nevertheless, it is imperative to conduct larger scale and randomized controlled studies to determine whether these complementary interventions have a significant additive or synergistic effect toward achieving complete recovery in the patients.
Chronic Stress Exacerbates Hyperglycemia-Induced Affective Symptoms in Male Mice
Authors: McCready Riley G. , Gilley Kayla R. , Kusumo Laura E. , Hall Grace M. , Vichaya Elisabeth G.
Published: October 2023

Introduction: Among chronically ill populations, affective disorders remain underdiagnosed and undertreated. A high degree of comorbidity exists between diabetes and affective disorders, particularly depression and anxiety. The mechanisms underlying stress-induced affective dysregulation are likely distinct from those induced by diabetes. A direct comparison between stress- and hyperglycemia-induced affective dysregulation could provide insight into distinct mechanistic targets for depression/anxiety associated with these different conditions. Methods: To this end, the present study used male C57BL/6J mice to compare the independent and combined behavioral and neuroinflammatory effects of two models: (1) unpredictable chronic mild stress and (2) pharmacologically induced hyperglycemia. Results: Streptozotocin-induced hyperglycemia was associated with a set of behavioral changes reflective of the neurovegetative symptoms of depression (i.e., reduced open field activity, reduced grooming, increased immobility in the forced swim task, and decreased marble burying), increased hippocampal Bdnf and Tnf expression, and elevations in frontal cortex Il1b expression. Our chronic stress protocol produced alterations in anxiety-like behavior and decreased frontal cortex Il1b expression. Discussion: While the combination of chronic stress and hyperglycemia produced limited additive effects, their combination exacerbated total symptom burden. Overall, the data indicate that stress and hyperglycemia induce different symptom profiles via distinct mechanisms.
Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug–Gene Networks: From Biology to Precision Therapeutics
Authors: Decano Julius L. , Maiorino Enrico , Matamalas Joan T. , Chelvanambi Sarvesh , Tiemeijer Bart M. , Yanagihara Yoshihiro , Mukai Shin , Jha Prabhash Kumar , Pestana Diego V.S. , D’Souza Edwin , Whelan Mary , Ge Rile , Asano Takaharu , Sharma Amitabh , Libby Peter , Singh Sasha A. , Aikawa Elena , Aikawa Masanori
Published: October 2023

BACKGROUND:

Interferon-γ (IFNγ) signaling plays a complex role in atherogenesis. IFNγ stimulation of macrophages permits in vitro exploration of proinflammatory mechanisms and the development of novel immune therapies. We hypothesized that the study of macrophage subpopulations could lead to anti-inflammatory interventions.

METHODS:

Primary human macrophages activated by IFNγ (M(IFNγ)) underwent analyses by single-cell RNA sequencing, time-course cell-cluster proteomics, metabolite consumption, immunoassays, and functional tests (phagocytic, efferocytotic, and chemotactic). RNA-sequencing data were analyzed in LINCS (Library of Integrated Network-Based Cellular Signatures) to identify compounds targeting M(IFNγ) subpopulations. The effect of compound BI-2536 was tested in human macrophages in vitro and in a murine model of atherosclerosis.

RESULTS:

Single-cell RNA sequencing identified 2 major clusters in M(IFNγ): inflammatory (M(IFNγ)

i

) and phagocytic (M(IFNγ)

p

). M(IFNγ)

i

had elevated expression of inflammatory chemokines and higher amino acid consumption compared with M(IFNγ)

p

. M(IFNγ)

p

were more phagocytotic and chemotactic with higher Krebs cycle activity and less glycolysis than M(IFNγ)

i

. Human carotid atherosclerotic plaques contained 2 such macrophage clusters. Bioinformatic LINCS analysis using our RNA-sequencing data identified BI-2536 as a potential compound to decrease the M(IFNγ)

i

subpopulation. BI-2536 in vitro decreased inflammatory chemokine expression and secretion in M(IFNγ) by shrinking the M(IFNγ)

i

subpopulation while expanding the M(IFNγ)

p

subpopulation. BI-2536 in vivo shifted the phenotype of macrophages, modulated inflammation, and decreased atherosclerosis and calcification.

CONCLUSIONS:

We characterized 2 clusters of macrophages in atherosclerosis and combined our cellular data with a cell-signature drug library to identify a novel compound that targets a subset of macrophages in atherosclerosis. Our approach is a precision medicine strategy to identify new drugs that target atherosclerosis and other inflammatory diseases.
Improved Cardiac Performance and Decreased Arrhythmia in Hypertrophic Cardiomyopathy With Non–β-Blocking R-Enantiomer Carvedilol
Authors: Seo Kinya , Yamamoto Yuta , Kirillova Anna , Kawana Masataka , Yadav Sunil , Huang Yong , Wang Qianru , Lane Kerry V. , Pruitt Beth L. , Perez Marco V. , Bernstein Daniel , Wu Joseph C. , Wheeler Matthew T. , Parikh Victoria N. , Ashley Euan A.
Published: October 2023

BACKGROUND:

Hypercontractility and arrhythmia are key pathophysiologic features of hypertrophic cardiomyopathy (HCM), the most common inherited heart disease. β-Adrenergic receptor antagonists (β-blockers) are the first-line therapy for HCM. However, β-blockers commonly selected for this disease are often poorly tolerated in patients, where heart-rate reduction and noncardiac effects can lead to reduced cardiac output and fatigue. Mavacamten, myosin ATPase inhibitor recently approved by the US Food and Drug Administration, has demonstrated the ability to ameliorate hypercontractility without lowering heart rate, but its benefits are so far limited to patients with left ventricular (LV) outflow tract obstruction, and its effect on arrhythmia is unknown.

METHODS:

We screened 21 β-blockers for their impact on myocyte contractility and evaluated the antiarrhythmic properties of the most promising drug in a ventricular myocyte arrhythmia model. We then examined its in vivo effect on LV function by hemodynamic pressure–volume loop analysis. The efficacy of the drug was tested in vitro and in vivo compared with current therapeutic options (metoprolol, verapamil, and mavacamten) for HCM in an established mouse model of HCM (
Myh6
R403Q
/+
and induced pluripotent stem cell (iPSC)-derived cardiomyocytes from patients with HCM (
MYH7
R403Q/+
).

RESULTS:

We identified that carvedilol, a β-blocker not commonly used in HCM, suppresses contractile function and arrhythmia by inhibiting RyR2 (ryanodine receptor type 2). Unlike metoprolol (a β
1
-blocker), carvedilol markedly reduced LV contractility through RyR2 inhibition, while maintaining stroke volume through α
1
-adrenergic receptor inhibition in vivo. Clinically available carvedilol is a racemic mixture, and the R-enantiomer, devoid of β-blocking effect, retains the ability to inhibit both α
1
-receptor and RyR2, thereby suppressing contractile function and arrhythmias without lowering heart rate and cardiac output. In
Myh6
R403Q/+
mice, R-carvedilol normalized hyperdynamic contraction, suppressed arrhythmia, and increased cardiac output better than metoprolol, verapamil, and mavacamten. The ability of R-carvedilol to suppress contractile function was well retained in
MYH7
R403Q/+
iPSC-derived cardiomyocytes.

CONCLUSIONS:

R-enantiomer carvedilol attenuates hyperdynamic contraction, suppresses arrhythmia, and at the same time, improves cardiac output without lowering heart rate by dual blockade of α
1
-adrenergic receptor and RyR2 in mouse and human models of HCM. This combination of therapeutic effects is unique among current therapeutic options for HCM and may particularly benefit patients without LV outflow tract obstruction.
Early Left Ventricular Unloading or Conventional Approach After Venoarterial Extracorporeal Membrane Oxygenation: The EARLY-UNLOAD Randomized Clinical Trial
Authors: Kim Min Chul , Lim Yongwhan , Lee Seung Hun , Shin Yoonmin , Ahn Joon Ho , Hyun Dae Young , Cho Kyung Hoon , Sim Doo Sun , Hong Young Joon , Kim Ju Han , Jeong Myung Ho , Jung Yong Hun , Jeong In-Seok , Ahn Youngkeun
Published: October 2023

BACKGROUND:

Although venoarterial extracorporeal membrane oxygenation (VA-ECMO) is beneficial for the treatment of profound cardiogenic shock, peripheral VA-ECMO cannulation can increase left ventricular afterload, thus compromising myocardial recovery. We investigated whether early routine left ventricular unloading can reduce 30-day mortality compared with the conventional approach in patients with cardiogenic shock undergoing VA-ECMO.

METHODS:

This randomized clinical trial involved 116 patients with cardiogenic shock undergoing VA-ECMO from March 2021 to September 2022 at Chonnam National University Hospital, Gwangju, South Korea. The patients were randomly assigned to undergo either early routine left ventricular unloading with transseptal left atrial cannulation within 12 hours after randomization (n=58) or the conventional approach, which permitted rescue transseptal left atrial cannulation in case of an increased left ventricular afterload (n=58). The primary outcome was all-cause mortality within 30 days.

RESULTS:

All 116 randomized patients (mean age, 67.6±13.5 years; 34 [29.3%] women) completed the trial. At 30 days, all-cause death had occurred in 27 (46.6%) patients in the early group and 26 (44.8%) patients in the conventional group (hazard ratio, 1.02 [95% CI, 0.59–1.74];
P
=0.942). Crossover to rescue transseptal left atrial cannulation occurred in 29 patients (50%) in the conventional group according to a clear indication. Time to rescue transseptal cannulation in the conventional group was a median of 21.8 (interquartile range, 12.4–52.2) hours after randomization. There were no significant differences in other secondary outcomes between the 2 groups except for a shorter time to disappearance of pulmonary congestion in the early group (median, 3 [interquartile range, 2–6] versus 5 [interquartile range, 3–7] days;
P
=0.027).

CONCLUSIONS:

Among patients with cardiogenic shock undergoing VA-ECMO, early routine left ventricular unloading with transseptal left atrial cannulation did not reduce 30-day mortality compared with the conventional strategy, which permitted rescue transseptal left atrial cannulation. These findings should be cautiously interpreted until the results of multicenter trials using other unloading modalities become available.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04775472.
Real‐World Effectiveness of PCSK9 Inhibitors in Reducing LDL‐C in Patients With Familial Hypercholesterolemia in Italy: A Retrospective Cohort Study Based on the AIFA Monitoring Registries
Authors: Arca Marcello , Celant Simone , Olimpieri Pier Paolo , Colatrella Antonietta , Tomassini Luca , D'Erasmo Laura , Averna Maurizio , Zambon Alberto , Catapano Alberico Luigi , Russo Pierluigi
Published: October 2023

Background

Information on the real‐world use of proprotein convertase subtilisin kexin 9 inhibitors (PCKS9is) in familial hypercholesterolemia are limited. We evaluated the pattern of prescription and the long‐term efficacy of alirocumab and evolocumab in Italian patients with familial hypercholesterolemia in clinical practice.

Methods and Results

The data set for analysis was extracted from the PCKS9i Italian Medicines Agency (AIFA) registry and included 2484 patients with heterozygous familial hypercholesterolemia (HeFH) and 62 patients with homozygous familial hypercholesterolemia (HoFH) who were prescribed PCKS9is from February 2017 to December 2021. As the follow‐up schedules were not prespecified and could vary, persistence and adherence as well as low‐density lipoprotein cholesterol (LDL‐C) changes during 2 years of treatment were analyzed in a final cohort of 1299 patients with familial hypercholesterolemia. At baseline, 53.8% of patients with HeFH and 69.4% of patients with HoFH were receiving maximally tolerated lipid‐lowering therapies, while 45.9% of patients with HeFH and 30.7% of patients with HoFH reported statin intolerance; mean LDL‐C was 197.7±52.3 mg/dL in HeFH and 252.0±106.2 mg/dL in HoFH. The 6‐month persistence and adherence to therapy were >85%, and LDL‐C reduction reached 58.6% (to 79.7 mg/dL) in HeFH and 57.6% (to 95.1 mg/dL) in HoFH after 24 months of treatment. The European Atherosclerosis Society/European Society of Cardiology LDL‐C goals were achieved in 43.3% of patients with HeFH and 37.5% of patients with HoFH.

Conclusions

PCKS9i prescribed to patients with familial hypercholesterolemia in clinical practice showed LDL‐C–lowering efficacy similar to that observed in controlled trials. However, 2 of 5 HeFH cases and 2 of 6 HoFH cases achieved the recommended LDL‐C goals. The full achievement of European Atherosclerosis Society/European Society of Cardiology LDL‐C goals should require a lower threshold for PCKS9i initiation and a combination of multiple therapies.
Spodocybe umbilicata (Hygrophoraceae, Agaricales), a newly discovered species from subtropical China
Authors: XIAO YING-QUN , LI HAI-JIAO , LI SAI-NAN , CHEN ZUO-HONG , ZHANG PING , HE ZHENG-MI
Published: October 2023

Spodocybe is a recently established genus with many potential species yet to be discovered. The present study reports a new species of Spodocybe collected from subtropical China, whose delimitation is supported by both morphological and phylogenetic evidence. The species is characterized by its small umbilicate pileus with a greyish brown, finely felty surface, white decurrent lamellae, finely fibrillose stipe concolorous with the pileal surface, and elongate to cylindrical basidiospores measuring 6.0–9.0 × 3.0–4.5 μm. In addition, a worldwide key to the known Spodocybe species is provided.
Typification of the name Dianema harveyi (Dianemataceae)
Authors: RONIKIER ANNA
Published: October 2023

Revision of available syntypes of Dianema harveyi Rex revealed that two of them represent another species, Prototrichia metallica. In order to clarify the species interpretation, Dianema harveyi is typified, described based on original material, and illustrated.