bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and Systemic Epigenetic Inheritance: Integrating Development, Genetics, and Evolution
Authors: Lickliter Robert , Moore David S.
Published: October 2023

Currently, a central problem for theoretical biology is the integration of development with genetics and evolutionary theory. Through the late 20th century, biologists held that animals resemble their ancestors strictly because of the transgenerational transmission of DNA. This view effectively wrote development out of evolutionary biology. However, many molecular and developmental biologists now understand that phenotypes – anatomical, physiological, and behavioral traits – are not determined by genes (i.e., DNA segments) alone; instead, they emerge epigenetically from developmental processes involving co-acting genetic factors, environmental factors, molecular epigenetic factors, and other non-genetic factors within organisms’ bodies. This insight forces a rethinking of biological inheritance. Perspectives focusing on the dynamics of developmental systems offer a compelling alternative way to think about inheritance, providing a powerful substitute to the reductionistic framework that attributes phenotypic outcomes to genetic instructions set in advance of developmental processes. Rethinking genetics, epigenetics, and inheritance by focusing on the dynamics of developmental systems helps highlight the bidirectional effects of evolutionary and developmental processes on one another, yielding a more integrated understanding of development, inheritance, and evolution. Simultaneously, this approach encourages rejection of genetic determinism, a simplistic perspective that continues to appear in psychological writing, despite its biological implausibility.
Co-Occurrence of Myotonic Dystrophy Type 1 and Limb-Girdle Muscular Dystrophy Type 2B: A Case Report
Authors: Hauschild Lucas Augusto , Seixas Maia da Silva Taciana , Winckler Pablo Brea , Moreira Cardoso-Júnior Laércio , Saute Jonas Alex Morales , Donis Karina Carvalho
Published: October 2023

Introduction: Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disease whose pattern of weakness is predominantly distal. Limb-girdle muscular dystrophy type 2B/R2-dysferlin-related (LGMD2B/R2) is another neuromuscular disease, which presents an autosomal recessive inheritance and is marked by proximal muscle weakness. Even if uncommon, comorbid inherited pathologies must be considered in cases of atypical presentations, especially in those with family history of consanguinity. Case Presentation: Herein, we report the unique case of a patient diagnosed with both DM1 and LGMD2B/R2: a 38-year-old woman in follow-up of DM1 in a neuromuscular disease service presenting prominent proximal weakness. The patient’s parents were consanguineous, and creatine kinase levels were elevated. A multi-gene panel test was performed and revealed the diagnosis of LGMD2B/R2. Conclusion: Genetic diseases with atypical presentations should raise the possibility of a second disorder, prompting an appropriate investigation. Overlooking a second diagnosis can implicate in not offering adequate genetic counseling, support, or specific treatment.
Pulmonary Enteric Adenocarcinoma: A Very Rare Case Report from Qatar
Authors: Yasin Ahmed K.A. , Mohamed Abdelaziz , Mohamed Anas , Elamin Nusiba , Al-Tikrity Mustafa A. , Wazwaz Bara
Published: October 2023

A 78-year-old male patient presented with dyspnea, loss of appetite, and weight loss. Workup and imaging showed suspected malignant lung lesion. Biopsy was done and showed features of pulmonary enteric adenocarcinoma (PEAC). This is a very rare disease and its diagnosis is challenging.
Acute V3 Hypesthesia following Laser Interstitial Thermal Therapy for Drug-Resistant Epilepsy
Authors: Lam Jordan L.W. , Levin Emily L.
Published: October 2023

Three studies have reported trigeminal hypesthesia following temporal lobe resection. However, no cases of hypesthesia have been reported following laser interstitial thermal therapy (LITT). We report the first case of trigeminal hypesthesia as a complication of otherwise successful LITT in a patient with drug-resistant epilepsy. A 58-year-old male with drug-resistant epilepsy secondary to a left parahippocampal gyrus multinodular and vacuolating neuronal tumor underwent biopsy and MRI-guided LITT. Immediately postoperatively, the patient reported hypesthesia in the left V3 distribution, including inside the mouth and ear. At 6-month follow-up, hypesthesia was present but improving, and the patient was seizure-free. While the cerebellopontine angle and prepontine cisterns are considered thermal insulators, we hypothesize that thermal injury was conducted through these spaces to the cisternal segment of the trigeminal nerve or to the inferior V3 branch in Meckel’s cave. Moreover, real-time visualization of the ablation is impacted by a blind spot at the skull base, created from bone disruption of MRI thermography.
Effect of Time Window on Endovascular Thrombectomy with or without Intravenous Thrombolysis in Acute Ischemic Stroke: Results from DIRECT-MT
Authors: Deng Qiwen , Zhang Lei , Liu Yukai , Zhou Feng , Yuan Zhenhua , Wang Xixi , Gao Jie , Yang Pengfei , Zhang Yongwei , Xing Pengfei , Li Zifu , Hong Bo , Han Hongxing , Shi Huaizhang , Shi Hongchao , Liu Jianmin ,   DIRECT-MT Investigators
Published: October 2023

Introduction: Whether time window affects the intravenous thrombolysis (IVT) effect before endovascular thrombectomy (EVT) is uncertain. We aimed to investigate the effect of different time windows (0–3 h and >3–4.5 h from stroke onset to randomization) on clinical outcomes of EVT with or without IVT in a subgroup analysis of DIRECT-MT. Methods: The primary outcome was the 90-day modified Rankin Scale (mRS) according to time window. Logistic regression models were used to analyze the effect of different treatments (EVT with or without IVT) on outcomes within 0–3 h or >3–4.5 h. Results: Among 656 patients who were included in the analysis, 282 (43.0%) were randomized within >3–4.5 h after stroke onset (125 without IVT and 157 with IVT), and 374 (57.0%) were randomized within 0–3 h (202 without IVT and 172 with IVT). We noted no significant difference in the thrombectomy-alone effect between the time window subgroups according to 90-day ordinal mRS (adjusted common odds ratio [acOR] in patients within 0–3 h: 1.06 [95% CI: 0.73–1.52], acOR in patients within >3–4.5 h: 1.19 [95% CI: 0.78–1.82]) and 90-day functional independence. Thrombectomy alone resulted in an increased proportion of patients with 90-day mRS 0–3 treated within >3–4.5 h (62.90 vs. 48.72%) but not within 0–3 h (65.84 vs. 63.95%). However, there was no interaction effect regarding all outcomes after the Bonferroni correction. Conclusions: Our results did not support thrombectomy-alone administration within 3–4.5 h in patients with acute ischemic stroke from large-vessel occlusion in the subgroup analysis of DIRECT-MT.
Validity of Lichen Planus and Lichen Planopilaris Case Identification Using Diagnostic Codes from a Clinical Database
Authors: Pelet del Toro Natalia , Strunk Andrew , Garg Amit , Han George
Published: October 2023

Background: Case identification strategies to conduct population-based studies have not been developed for lichen planus (LP) or lichen planopilaris (LPP). Objectives: The aim of this study was to assess the validity of using diagnostic codes to establish both a cutaneous (non-oral) LP cohort and an LPP cohort from a large clinical database. Methods: A retrospective chart review was performed to determine whether patients with ICD-9 or ICD-10 codes for LP and ICD-10 codes for LPP are confirmed cases of LP and LPP. Validation samples were used to estimate the positive predictive value (PPV) of three case definitions any LP, non-oral LP, and LPP defined as: at least one code by any physician, at least two codes by any physician, and at least one code by a dermatologist. Results: Among the 199 reviewed LP charts, 166 and 123 were confirmed cases of any LP and non-oral LP, respectively. The PPVs for any LP were: 83.4% (166/199) for one code by any physician, 84.6% (77/91) for two codes by any physician, and 95.1% (97/102) for one code by a dermatologist. The PPVs for non-oral LP were: 61.8% (123/199) for one code by any physician, 70.3% (64/91) for two diagnoses by any physician, and 86.3% (88/102) for one diagnosis by a dermatologist. Of the 139 patients with at least one code for LPP, 122 were confirmed cases of LPP. The case definition for one LPP code applied by any physician had a PPV of 87.8% (122/139) to identify a true case of LPP, whereas two diagnoses by any physician had a PPV of 96.2% (76/79) and a diagnosis by a dermatologist had a PPV of 93% (107/115). Conclusions: Diagnosis codes for LP and LPP, restricted by the diagnosing physician’s specialty, may be used to accurately identify case cohorts of overall LP, non-oral LP, or LPP in large clinical databases.
Emergence of New Concepts in Skin Physiopathology through the Use of in vitro Human Skin Explants Models
Authors: Cousin Ianis , Misery Laurent , de Vries Philine , Lebonvallet Nicolas
Published: October 2023

Background: This review summarizes uses and new applications for dermatological research of in vitro culture models of human skin explants (HSEs). In the last decade, many innovations have appeared in the literature and an exponential number of studies have been recorded in various fields of application such as process culture engineering, stem cell extractions methodology, or cell-to-cell interaction studies under physiological and pathological conditions, wound-healing, and inflammation. Most studies also concerned pharmacology, cosmetology, and photobiology. However, these topics will not be considered in our review. Summary: A better understanding of the mechanisms driving intercellular relationships, at work in the maintenance of 3D tissue architectures has led to the improvement of cell culture techniques. Many papers have focused on the physiological ways that govern in vitro tissue maintenance of HSEs. The analysis of the necessary mechanical stress, intercellular and cell-matrix interactions, allows the maintenance and prolonged use of HSEs in culture for up to 15 days, regardless of the great variability of study protocols from one laboratory to another and in accordance with the objectives set. Because of their close similarities to fresh skin, HSEs are increasingly used to study skin barrier repair and wound healing physiology. Easy to use in co-culture, this model allows a better understanding of the connections and interactions between the peripheral nervous system, the skin and the immune system. The development of the concept of an integrated neuro-immuno-cutaneous system at work in skin physiology and pathology highlighted by this article represents one of the new technical challenges in the field of in vitro culture of HSE. This review of the literature also reveals the importance of using such models in pathology. As sources of stem cells, HSEs are the basis for the development of new tissue engineering models such as organoids or optical clearing tissues technology. This study identifies the main advances and cross-cutting issues in the use of HSE.
Menstrual Status Is Associated with the Prevalence of Irritable Bowel Syndrome in a Japanese Young Population: A Cross-Sectional Study
Authors: Furukawa Shinya , Yamamoto Yasunori , Miyake Teruki , Yoshida Osamu , Watanabe Junichi , Kato Aki , Kusumoto Katsunori , Takeshita Eiji , Ikeda Yoshio , Yamamoto Naofumi , Saeki Yuka , Hiasa Yoichi
Published: October 2023

Introduction: There is evidence regarding the association between dysmenorrhea and irritable bowel syndrome (IBS), although it is lacking in the Asian population. Therefore, the purpose of this study was to investigate the association between menstrual status and IBS in a young Japanese. Methods: Overall, 4,693 female college students were included in the analysis of this study. Information regarding lifestyle habits, menstrual status (irregularity, pain severity, and medication), and IBS (Rome III criteria) was obtained using a self-reported questionnaire. Age, body mass index, exercise habits, smoking, drinking habits, and anemia were analyzed as potential confounders. Results: The prevalence of IBS was 6.1%. Moderate {adjusted odds ratio (OR): 1.89 (95% confidence interval [CI]: 1.27–2.91)} and heavy (adjusted OR: 2.14 [95% CI: 1.42–3.45]) menstrual pain were independently positively associated with IBS (p for trend = 0.001). Using medication sometimes (adjusted OR: 1.41 [95% CI: 1.09–1.84]) and often (adjusted OR: 1.60 [95% CI: 1.13–2.24]) was independently positively associated with IBS. There was no association between menstrual cycle and IBS. In subjects without functional dyspepsia, irregular menstrual cycle was independently positively associated with IBS. Conclusion: In the young Japanese population, menstrual pain and medications for menstrual pain may have a significant positive association with IBS.
Management of the Rectal Stump after Subtotal Colectomy Operations for Inflammatory Bowel Disease in the Era of Immunologic Therapy: A Two-Centre Cohort Study
Authors: Boldovjakova Dominika , El-Abbassy Islam , Alarcon Inari , El-Saify Mamoun , Chan Juen Hao , Harley Morag , Parnaby Craig , Watson Angus , Ramsay George
Published: October 2023

Introduction: Inflammatory bowel disease (IBD) often requires surgical resection, such as subtotal colectomy operations to alleviate symptoms. However, IBD also has an inherently increased risk of colorectal dysplasia and cancer. Despite the well-accepted surveillance guidelines for IBD patients with an intact colon, contemporaneous decision-making models on rectal stump surveillance is sparse. This study looks at the fate of rectal stumps in IBD patients following subtotal colectomy. Methods: This is a two-centre retrospective observational cohort study. Patients were identified from NHS Grampian and NHS Highland surgical IBD databases. Patients that had subtotal colectomy between January 01, 2010 and December 31, 2017 were included with the follow-up end date on April 1, 2021. Socio-demographics, diagnosis, medical and surgical management data were collected from electronic records. Results: Of 250 patients who had subtotal colectomy procedures, only one developed a cancer in their rectal stump (0.4%) over a median follow-up of 80 months. A higher than expected 72% of patients had ongoing symptoms from their rectal stumps. Surveillance was varied and inconsistent. However, no surveillance, flexible sigmoidoscopy, or MRI identified dysplastic or neoplastic disease. Conclusion: Based on our results, we estimate that the prevalence of rectal cancer is lower than previously reported. Surveillance strategy of rectal stump varied as no current guidelines exist and hence is an important area for future study. Given the relatively low frequency of rectal cancer in these patients, and the low level of evidence available in this field, we would propose a registry-based approach to answering this important clinical question.
Brain Neuropeptides, Neuroinflammation, and Irritable Bowel Syndrome
Authors: Ishioh Masatomo , Nozu Tsukasa , Okumura Toshikatsu
Published: October 2023

Background: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by chronic abdominal symptoms, but its pathogenesis is not fully understood. Summary: We have recently shown in rats that neuropeptides such as orexin, ghrelin, and oxytocin act in the brain to improve the intestinal barrier dysfunction, which is a major pathophysiology of IBS. We have additionally shown that the neuropeptides injected intracisternally induced a visceral antinociceptive action against colonic distension. Since it has been known that intestinal barrier dysfunction causes visceral hypersensitivity, the other main pathophysiology of IBS, the neuropeptides act centrally to reduce leaky gut, followed by improvement of visceral sensation, leading to therapeutic action on IBS. It has been recently reported that there is a bidirectional relationship between neuroinflammation in the brain and the pathophysiology of IBS. For example, activation of microglia in the brain causes visceral hypersensitivity. Accumulating evidence has suggested that orexin, ghrelin, or oxytocin could improve neuroinflammation in the CNS. All these results suggest that neuropeptides such as orexin, ghrelin, and oxytocin act in the brain to improve intestinal barrier function and visceral sensation and also induce a protective action against neuroinflammation in the brain. Key Messages: We therefore speculated that orexin, ghrelin, or oxytocin in the brain possess dual actions, improvement of visceral sensation/leaky gut in the gut, and reduction of neuroinflammation in the brain, thereby inducing a therapeutic effect on IBS in a convergent manner.
Comprehensive Questionnaire in Postpartum Women to Assess Women’s Knowledge of the Current Weight Gain Guidelines during Pregnancy in Lower Saxony
Authors: Dickert Jennifer Jessica , Mbang Springer Daliah Laura , von Kaisenberg Constantin , Hillemanns Peter , de Zwaan Martina , Brodowski Lars
Published: October 2023

Introduction: Maternal body mass index and gestational weight gain (GWG) are important factors for maternal and neonatal health. The objective of this study was to assess women’s knowledge and examine adherence to the Institute of Medicine (IOM) criteria for weight gain during pregnancy by evaluating the information received from obstetricians and women’s knowledge about GWG. Methods: This is an analytical semi-longitudinal observational study. Weight data from a nonconsecutive convenience sample of 389 women who gave birth at the Hannover Medical School in the period from August 2020 to July 2021 were taken from their maternal records. Immediately after giving birth, the whole collective (n = 389) was asked to participate in a questionnaire study including questions that were taken from the EMat Health Survey inquiring about their knowledge and received information about GWG and about their eating behavior. Here, a subset of 202 women participated. Results: Sixty-five percent of the participants who answered the questionnaire reported that they had not been informed by their obstetrician about GWG recommendations. Additionally, a minority of women knew the correct IOM GWG category based on their pre-pregnancy weight. Meeting the IOM GWG guidelines did not depend on whether or not women received GWG recommendations or knew about the correct GWG category. The majority of women were not concerned about gaining too much weight during pregnancy. 20.7% of all women participating in the study were affected by obesity pre-pregnancy. According to the IOM criteria for GWG, 50.4% gained too much weight. The proportion of women exceeding IOM recommendations was highest in women with pre-pregnancy overweight and obesity (67%). Discussion: Weight gain outside of the IOM recommendations is widespread in our survey. Information received and knowledge about GWG recommendations were inadequate in our sample. Considering the fact that GWG outside recommended ranges can contribute to short- and long-term health complications, especially when a woman enters pregnancy already with overweight or obesity, identifying ways of achieving a healthier GWG is warranted.
Intra-Abdominal Paraganglioma and Primary Thyroid Lymphoma in a Single Patient: The First Case Report
Authors: Zakkor Mohammed Deeb , Swed Sarya , Salem Rima , Zayat Hussein , Sultan Rasha , Al Hussein Hachem , Rezkallah Vairy , Nashwan Abdulqadir J.
Published: October 2023

Rare diseases such as primary thyroid lymphoma (PTL) and paragangliomas exist. Although only 0.5% of patients experience a transformation from thyroiditis to PTL, patients with Hashimoto’s thyroiditis have a higher risk of developing PTL than the general population. Primary non-Hodgkin lymphoma of the thyroid is rare. Paragangliomas are neuroendocrine tumors that originate from chromaffin cells situated along the sympathetic and parasympathetic chains. This paper reports the first case of primary diffuse large B-cell lymphoma with nonfunctional paraganglioma. A 29-year-old female presented with an enlarged neck and recurrent compressive symptoms. Ultrasonography results showed a nodule in the right lobe of the thyroid gland. Emergency thyroidectomy was performed after obtaining inconclusive fine-needle aspiration results. Immunohistopathology of the biopsy specimen confirmed the presence of a large diffuse B-cell lymphoma. Computed tomography revealed a nonfunctional mass in the adrenal gland. The team then proceeded with the appropriate treatment.
Induction of Vesicular Trafficking and JNK-Mediated Apoptotic Signaling in Mononuclear Leukocytes Marks the Immuno-Proteostasis Response to Uremic Proteins
Authors: Bartolini Desirée , Grignano Maria Antonietta , Piroddi Marta , Chiaradia Elisabetta , Galeazzi Gabriele , Rende Mario , Ronco Claudio , Rampino Teresa , Libetta Carmelo , Galli Francesco
Published: October 2023

Introduction: Uremic retention solutes have been alleged to induce the apoptotic program of different cell types, including peripheral blood mononuclear leukocytes (PBL), which may contribute to uremic leukopenia and immune dysfunction. Methods: The molecular effects of these solutes were investigated in uremic PBL (u-PBL) and mononuclear cell lines (THP-1 and K562) exposed to the high molecular weight fraction of uremic plasma (u-HMW) prepared by in vitro ultrafiltration with 50 kDa cut-off microconcentrators. Results: u-PBL show reduced cell viability and increased apoptotic death compared to healthy control PBL (c-PBL). u-HMW induce apoptosis both in u-PBL and c-PBL, as well as in mononuclear cell lines, also stimulating cellular H2O2 formation and secretion, IRE1-α-mediated endoplasmic reticulum stress signaling, and JNK/cJun pathway activation. Also, u-HMW induce autophagy in THP-1 monocytes. u-PBL were characterized by the presence in their cellular proteome of the main proteins and carbonylation targets of u-HMW, namely albumin, transferrin, and fibrinogen, and by the increased expression of receptor for advanced glycation end-products, a scavenger receptor with promiscuous ligand binding properties involved in leukocyte activation and endocytosis. Conclusions: Large uremic solutes induce abnormal endocytosis and terminal alteration of cellular proteostasis mechanisms in PBL, including UPR/ER stress response and autophagy, ultimately activating the JNK-mediated apoptotic signaling of these cells. These findings describe the suicidal role of immune cells in facing systemic proteostasis alterations of kidney disease patients, a process that we define as the immuno-proteostasis response of uremia.
Sympathetic Ophthalmia in Patients with Enucleation or Evisceration: Pathology Laboratory and IRIS® Registry Experience
Authors: Bui Khanh , Tomaiuolo Maurizio , Carter Kaylene , Iacob Codrin , Neerukonda Vamsee , Stagner Anna , Sajjadi Zaynab , Escobar Katherine V. , Ordoñez Armijos Paula , Eagle Ralph C. , Mehta Sonia , Dunn James P. , Hyman Leslie , Milman Tatyana ,   on behalf of the IRIS
Published: October 2023

Introduction: Sympathetic ophthalmia (SO) is a rare bilateral granulomatous panuveitis that can follow surgical or nonsurgical ocular trauma in one eye. Because its diagnosis requires clinical-pathologic correlation, the true incidence of SO is unknown, and there is a need to understand the recent trends in risk factors and frequency of this condition. Methods: Pathology records of all enucleated or eviscerated (ENEV) eyes at three pathology laboratories were reviewed. Data collected included patient demographics, procedure indication, pathology diagnosis, and clinical history of trauma and uveitis. IRIS® Registry (Intelligent Research in Sight) was searched for all patients with SO, acquired absence of eye (AAE), and/or ENEV. Data obtained included patient demographics, ocular procedures, and preoperative diagnoses within 30 days of AAE/ENEV. Results: In the pathology laboratory setting, the incidence of SO over a 36-year period in patients who underwent ENEV was 0.2% (20/9,092); the 5-year incidence ranged from 0.0 to 0.3%. Among the 20 eyes with SO, the inciting event was surgical trauma in 50% (10/20), nonsurgical trauma in 45% (9/20), and missing/undetermined in 5% (1/20). SO was suspected preoperatively in 7/20 (35%) patients. Clinical concern for SO and ruptured globe were indications for ENEV in 50/9,092 (0.5%) and 872/9,092 (10%) patients, respectively. In the IRIS Registry, 0.7% (199/27,830) of patients with AAE/ENEV had diagnosis of SO. The frequency of SO between 2015 and 2020 was 0.01% (7,371/62,318,249); of these 7,371 cases, 199 (3%) had AAE/ENEV. In 25,975 patients with available data, injury and SO were listed as diagnoses less than 30 days prior to AAE/ENEV in 909 (4%) and 63 (0.2%) cases, respectively. Conclusion: The frequency of SO in recent decades has been low. Most cases of SO are not managed with eye removal. In histopathology-confirmed SO, surgical trauma is as frequent as nonsurgical trauma as an inciting etiology of disease.
Airway Microbiome Composition and Co-Occurrence Network Are Associated with Inflammatory Phenotypes of Asthma
Authors: Li Yi , Zou Congying , Li Jieying , Wang Wen , Wang Feiran , Guo Yue
Published: October 2023

Introduction: The composition and co-occurrence network of the airway microbiome might influence the asthma inflammatory phenotype. Airway microbiota change with asthma phenotypes, and the structure of the bacterial community in the airway might differ between different asthma inflammatory phenotypes and may also influence therapy results. Identifying airway microbiota can help to investigate the role that microbiota play in the asthma inflammatory process. Methods: Induced sputum from 55 subjects and 12 healthy subjects from Beijing, China, was collected and analyzed for bacterial microbiota. Microbiome diversity, composition, co-occurrence networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were predicted and compared between the study groups. Results: Significant differences in the sputum microbiome composition, co-occurrence network, and predicted functional pathways were observed between the two inflammatory phenotypes. Asthmatics in the low FeNO group exhibited lower α-diversity in the sputum microbiota and had higher abundance of the phylum Proteobacteria compared with that of the high FeNO group. The network in the high FeNO group was more “closed” and “connected” compared with that of the low FeNO group, and an alteration in the abundance of keystone species T. socranskii was found. Significantly different predicted metabolic subfunctions including nucleotide metabolism, lipid metabolism, energy metabolism, replication and repair, and drug resistance antimicrobial and carbohydrate metabolism between the two studied phenotypes were also observed. Conclusion: Our findings confirm that the airway microbiota is associated with the asthma inflammation process. The differences in the airway microbiome composition and co-occurrence network may affect distinct asthma inflammatory phenotypes, suggesting the possibility that more targeted therapies could be applied based on the airway bacterial genera.
Interpretative Phenomenology of Grief following Reproductive Loss: A Narrative Review and Considerations on Improving Support
Authors: Facão Rita , Madeira Luís
Published: October 2023

The loss of pregnancy through miscarriage or stillbirth is typically an unexpected and highly distressing event for parents. While death in any form may be overwhelming to those bereaved, pregnancy and newborn loss are unique in several ways because they involve the added loss of parental identity and the idealized baby and family. In this study, the authors performed a narrative review of the literature regarding the phenomenon of grief following reproductive loss in bereaved parents, focusing on heteronormative mothers and fathers and on nontraditional families. One of the main highlighted aspects is the disenfranchisement of grief, which refers to a loss that is not or cannot be acknowledged, publicly mourned, or socially supported. This feeling is elicited by family, society, and healthcare providers. Although the literature has consistently documented the negative impact of this type of experience on parents and families, it is still largely unrecognized by healthcare providers. As most studies demonstrate, there are significant gaps in the psychosocial components of miscarriage and stillbirth care, including a lack of clarity in communication about the loss and subsequent steps, a lack of empathy, an invalidation of grief, and a failure to attend to emotional needs. Since healthcare providers are most often the first point of contact as they experience the loss, it is imperative to act so that patients’ needs are more adequately met. To this purpose, the authors propose a set of measures aimed at improving the quality of care and support.
Liver Biopsy: To Do or Not to Do – A Single-Center Study
Authors: Androutsakos Theodoros , Dimitriadis Konstantinos , Revenas Konstantinos , Vergadis Chrysovalantis , Papadakis Dimitrios-Dorotheos , Sakellariou Stratigoula , Vallilas Christos , Hatzis Gregorios
Published: October 2023

Introduction: A variety of liver disorders are associated with characteristic histopathological findings that help in their diagnosis and treatment. However, percutaneous liver biopsy (PLB) is prone to limitations and complications. We evaluated all PLBs done in our hospital in a 13-year period, aiming to assess PLB’s utility and complications. Methods: All PLBs conducted in an internal medicine department of a tertiary university hospital in Athens, Greece, during a 13-year period were reviewed. Recorded data included demographic characteristics, laboratory results acquired on biopsy day, indication for liver biopsy, and occurrence of side effects. All patients were followed for 1 month post-hospital discharge for possible PLB-related complications. Results: A total of 261 patients underwent PLB during the study period. The commonest indication of PLB was investigation of liver mass, followed by transaminasemia. PLB assisted in setting a diagnosis in 218 patients and was unhelpful in only 43, in 14 of them due to inadequate or inappropriate biopsy specimen. Complications attributable to PLB were rare, with 10 patients exhibiting pain, either at biopsy site or in the right shoulder, and 3 having bleeding episodes; no deaths were noted. Conclusions: Our study shows that PLB is still a powerful diagnostic tool in everyday practice, provided it is used when indicated.
Survival Outcomes of Mohs Surgery versus Wide Local Excision for Less Common Nonmelanoma Skin Cancers: A Stabilized Inverse Probability of Treatment Weighting Analysis
Authors: Chen Ming , Yunqiong Wang Yunqiong
Published: October 2023

Background: Compared with wide local excision (WLE), Mohs micrographic surgery (MMS) can not only remove the tumor tissue but also ensure a negative margin. However, there is limited evidence on whether there is a difference in prognosis between the two techniques for less common nonmelanoma skin cancers (NMSCs). Objectives: The aim of our study was to compare the survival outcomes of MMS and WLE for less common NMSCs. Methods: This study retrospectively analyzed data from the Surveillance, Epidemiology, and End Results dataset between 2003 and 2018. The less common NMSCs include Merkel cell carcinoma, skin appendage neoplasm, fibromatous malignancy, and other rare NMSCs. The stabilized inverse probability of treatment weighting (SIPTW) and the Kaplan-Meier methods were adopted to assess the overall survival (OS) and cancer-specific survival (CSS). Furthermore, the Cox proportional hazards, Fine-and-Gray regression analysis, and subgroup analysis models were applied to examine the effects of MMS versus WLE based on all-cause and cancer-specific mortality. Results: We identified 6,582 individuals with less common NMSCs for survival analysis, among which 1,946 patients (29.5%) had undergone MMS and 4,636 (70.5%) had received WLE. Diseases diagnosed in the most recent year, older age, the White race, married status, eyelid/face site, small tumor size, and localized disease were factors significantly associated with MMS treatment. Compared with the WLE group, the MMS group had comparable OS before and after the SIPTW analysis. Additionally, after adjusting for other confounding covariates, the surgery type (WLE vs. MMS) did not show significant associations with all-cause mortality (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 0.94–1.14, p = 0.517) and disease-specific mortality (HR: 1.16, 95% CI: 0.95–1.42, p = 0.134). Moreover, the subgroup analysis validated these findings. Conclusion: MMS and WLE have comparable OS and CSS for less common NMSCs.
Exocrine Pancreatic Insufficiency Possibly Related to Atypical Chronic Graft-versus-Host Disease
Authors: Hosokawa Yuka , Toubai Tomomi , Ohya Koichi , Nagano Yusuke , Ishizawa Yuki , Hosokawa Masashi , Sato Ryo , Watanabe Shotaro , Yamada Akane , Suzuki Takuma , Aizawa Keiko , Ito Satoshi , Onozato Yusuke , Peltier Daniel , Ishizawa Kenichi
Published: October 2023

We report the case of a 66-year-old woman who presented with diarrhea and weight loss approximately 14 months after unrelated allogeneic bone marrow transplantation for acute myeloid leukemia. Her early post-transplant course was notable for mild acute skin graft-versus-host disease (GVHD) and biopsy-proven upper gastrointestinal (GI) acute GVHD, both of which resolved with treatment. She then developed weight loss and diarrhea treated with prednisolone for what was thought to be GI late acute GVHD. However, her diarrhea and weight loss persisted. Colonoscopy showed a grossly intact mucosa, and stool studies only confirmed steatorrhea. However, an atrophic pancreas was found on an abdominal computed tomography (CT) scan. Exocrine pancreatic enzymes, such as lipase and pancreatic amylase, were markedly decreased, yet pancreatic endocrine function remained intact. The patient’s diarrhea and weight loss improved upon treatment with pancrelipase. Therefore, we suggest that her exocrine pancreatic insufficiency was likely partly caused by atypical chronic GVHD.
Encapsulated Papillary Carcinoma in an Elderly Male Whose Diagnosis Was Difficult before Surgery: A Case Report
Authors: Sugino Maho , Horimoto Yoshiya , Murakami Fumi , Takahashi Yuka , Ouchi Kazutomo , Sato Hideaki , Ishido Yasunori
Published: October 2023

Encapsulated papillary carcinoma (EPC) is a relatively rare histologic type of breast cancer. It is sometimes difficult to obtain a definitive diagnosis by needle biopsy, reflecting its characteristics as an intracystic lesion. Herein, we report a case of EPC in an elderly male that was difficult to diagnose before surgery. A 70-year-old man visited our hospital after a mass just under his right nipple that gradually increased in size. Ultrasonography revealed a well-defined intracystic 50 mm-sized tumor and a papillary-shaped solid component arising from the cyst wall. Cytology revealed small clusters of atypical cells suggestive of malignancy, but we did not reach a definitive diagnosis with subsequent vacuum-assisted needle biopsy due to the small amount of specimen. Given the imaging findings strongly suggested a malignant tumor, a mastectomy was performed. Histologically, there was a thick fibrous capsule and mildly atypical cells showed papillary growth, and we diagnosed the case as EPC (pTisNXM0). Sometimes, EPC is difficult to discriminate from intracystic papilloma before surgery, but clinicians should always keep in mind that this histological type exists with a certain frequency in male patients.
Clinical Value of Clip-and-Snare Assisted Endoscopic Submucosal Resection in Treatment of Rectal Neuroendocrine Tumors
Authors: Jiang Xin-Tong , Hu Yang , Gong Jian , Guo Shi-Bin
Published: October 2023

Introduction: The aim of the study was to introduce a new endoscopic technology, clip-and-snare assisted endoscopic submucosal resection (CS-ESMR), for treatment of rectal neuroendocrine tumors (NETs) and then to investigate the therapeutic value of CS-ESMR. Methods: In this retrospective study, 67 patients who underwent endoscopic treatment of rectal NETs from March 2017 to December 2021 were analyzed. According to the endoscopic resection methods (endoscopic mucosal resection [EMR], CS-ESMR, and endoscopic submucosal dissection [ESD]), the cases were divided into CS-ESMR group (27 cases), ESD group (31 cases), and EMR group (9 cases). The pathological R0 resection rate and the incidence of adverse events (bleeding and perforation) were compared among the three groups. Results: There was a significant difference about the pathological R0 resection between the CS-ESMR group and the EMR group and between the CS-ESMR group and the ESD group (both p < 0.05). Compared with ESD group, the procedure time, intraoperative bleeding, and the cost of CS-ESMR group are significantly decreased (p < 0.001, p < 0.05, p < 0.001, respectively). Conclusion: CS-ESMR may be a safe and effective treatment for rectal NETs with a diameter of less than 10 mm, without muscularis propria invasion and metastasis.
Chronic Spontaneous Urticaria in Belgium: Deciphering the Clinical Profile and Treatment of Patients Visiting an Urban City Immunology Department
Authors: Mostmans Yora , Richert Bertrand , De Maertelaer Viviane , Saidi Ines , Benslimane Asma , Thi Thanh Thao Tran , Corazza Francis , Michel Olivier
Published: October 2023

Background: Chronic urticaria (CSU) is a chronic inflammatory mast cell-driven disorder of which reliable clinical data in Belgium are lacking. This study focusses on clinical characteristics of CSU patients presenting at an urban Immunology-Allergology department. Methods: Outpatients with CSU were included from 2018 to 2021. Clinical characteristics, Dermatology Life Quality Index (DLQI) and Urticaria activity score (UAS7) were collected by thorough anamnesis and questionnaires. Furthermore, patients underwent provocational testing, an autologous serum skin test (ASST) and a blood analysis. Results: The study included 49 CSU patients and 20 non-CSU subjects. CSU was distributed differently with age and sex, showing higher numbers in female patients below the age of 46 years. 67% of CSU patients had accompanying angioedema of which 9% were reported genital. CSU patients scored a mean 8/30 on their DLQI questionnaire. There was no significant difference in immunoglobulin E (IgE), C-reactive protein, and tryptase levels between CSU patients and controls. Oral glucocorticosteroids were prescribed in 23% of CSU patients during their disease course though only half of these patients had a severity grade 4 CSU. In 82% of the included CSU patients, Urticaria Control Test (UCT) scores were below 12. When we hypothetically considered low IgE levels and high IgG anti-thyroid peroxidase levels as differentiation marker for autoimmune (ai)CSU and non-aiCSU, we found that 4% of all included CSU patients could be considered aiCSU. Conclusion: Generally, the inner-city population displayed the same clinical characteristics, as previous cohorts from Northern Europe. The relatively high rate of CSU patients receiving oral glucocorticosteroid treatment for their disease though not always classified as severe, underlines the need to train doctors of various specialties in the treatment algorithms of CSU. Furthermore, by looking at potential autoimmune characteristics, our findings open perspectives on the identification of new routinely used clinical parameters for the detection of aiCSU, a relatively small immunological subtype of CSU.
Low-Density Lipoprotein Cholesterol Is Associated with Atopic Dermatitis in Korean Adolescents
Authors: Seong Min Kyeong , Shin Meeyong
Published: October 2023

Introduction: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Several studies have investigated the relationship between obesity and AD prevalence, but the results have been conflicting. This study investigated the association between obesity and AD in Korean adolescents. Methods: We used nationally representative data regarding 1,617 Korean adolescents aged 12–18 years, which were obtained from the cross-sectional Korea National Health and Nutrition Examination Survey 2017–2019. Multiple logistic regression analysis (including age, sex, region of residence, number of household members, economic status, lipid profile, and stress level) was used to evaluate the relationships of obesity and abdominal obesity with doctor-diagnosed AD. Results: Although the results were not statistically significant, obese adolescents were diagnosed with AD (20.8%) more often than non-obese adolescents (20.8% vs. 14.5%, p = 0.055). This tendency was more prominent in male adolescents than in female adolescents, but the finding was not statistically significant. Body mass index and the prevalence of abdominal obesity did not differ between the AD and non-AD groups. Adolescents with AD had significantly higher total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, compared with adolescents who did not have AD. In the adjusted model, an LDL-C level ≥130 mg/dL was a risk factor for AD (adjusted odds ratio, 1.03; 95% confidence interval, 1.01–1.05). Conclusions: A high LDL-C level may be a risk factor for AD. Proper management of dyslipidemia through lifestyle modification may aid in AD prevention and control. Further large-scale prospective studies are needed to assess the associations of AD with obesity and dyslipidemia.
Correlation Analysis between Intrarenal Small Artery Intimal Thickening and Clinicopathological Features and Prognosis in Primary Membranous Nephropathy Patients
Authors: Cheng Yuan , Li Wangyang , Chen Jia , Qi Dongli , Guan Mijie , Cao Tao , Hu Haofei , Wu Liling , Rao Qingqing , Wan Qijun
Published: October 2023

Background: Primary membranous nephropathy (PMN) is the most common pathological type of nephrotic syndrome in adults. Intrarenal small artery intimal thickening can be observed in most renal biopsies. The purpose of this study was to investigate the association between intrarenal small artery intimal thickening and clinicopathological features and prognosis in PMN patients. Methods: Data were continuously collected from patients who were diagnosed with PMN in Shenzhen Second People’s Hospital (The First Affiliated Hospital of Shenzhen University) from 2008 to 2021 for a retrospective cohort study. Regression analysis and survival analysis were used to analyze the relationship between intrarenal small artery intimal thickening and renal prognosis in PMN patients. Results: 300 PMN patients were enrolled in this study, including 165 patients (55%) with intrarenal small artery intimal thickening. Patients with intimal thickening were older, with higher BMI, systolic blood pressure and diastolic blood pressure, serum uric acid, a higher proportion of hypertension, acute kidney injury, nephrotic syndrome, more urine protein, and lower eGFR. Multivariate Cox regression analysis showed that after adjusting for age, gender, hypertension, BMI, urine protein, eGFR, and the use of ACEI/ARB and hormone immunosuppressants, intimal thickening was a risk factor for renal prognosis in PMN patients (HR = 3.68, 95% CI 1.36–9.96, p < 0.05). Kaplan-Meier survival curve analysis showed that the incidence of reaching the renal composite outcome was higher in the intimal thickening group (p < 0.05). Conclusion: The prognosis of PMN patients with intrarenal small artery intimal thickening is worse, so early intervention is very important for these patients.
Results of a Phase Ib Study Investigating Durvalumab in Combination with Eribulin in Patients with HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian Cancer
Authors: Landry Chrystal A. , Blanter Julia , Ru Meng , Fasano Julie , Klein Paula , Shao Theresa , Bhardwaj Aarti , Tiersten Amy
Published: October 2023

Introduction: The release of tumor-associated antigens with cytotoxic chemotherapy treatment may enhance the response to immune checkpoint blockade. Eribulin is a microtubule inhibitor with proven overall survival (OS) benefit in metastatic breast cancer (MBC), which may also enhance intratumoral vascular remodeling. Durvalumab, a humanized monoclonal antibody, targets the programmed cell death ligand-1 (PD-L1) receptor. This study sought to determine the maximum tolerated dose and recommended phase II dose (RP2D) of eribulin in combination with durvalumab, as well as the safety and preliminary antitumor activity of the combination in patients with previously treated HER2-negative (HER2−) MBC and recurrent ovarian cancer (ROC). Methods: Cohorts of 3–6 patients with HER2− MBC and ROC were treated in a modified 3+3 design. Eligible patients received escalating doses of eribulin (1.1 mg/m2 or 1.4 mg/m2 IV on day 1 and day 8) with durvalumab (1.12 g IV on day 1) in 21-day cycles until dose-limiting toxicity (DLT), intolerable adverse events (AEs), disease progression, or other reasons for withdrawal. Primary endpoint: the rate of DLTs during cycles 1 and 2 of therapy. Secondary endpoints: AE rate, objective response rate (ORR), progression-free survival (PFS), and OS. Results: Nine patients with a median of 4 prior therapies for advanced disease were treated: 5 patients with HER2− MBC (1 with triple-negative disease and 4 with hormone-positive disease) and 4 patients with ROC. The RP2D of eribulin was 1.4 mg/m2 in combination with durvalumab. There were no DLTs experienced during the first two cycles of therapy. The most common treatment-related AEs (>50%) were fatigue, neutropenia, decreased white blood cell count, anemia, AST and alkaline phosphatase elevation, hyperglycemia, and nausea; most were grade 1 or 2. There was one immune-related AE of grade 3 (hepatitis) after 5 cycles of treatment, for which patient came off study. Two other patients discontinued study drug related to toxicity (neutropenia [n = 1], hepatic toxicity [n = 1]). ORR was 55%, and 4 additional patients experienced stable disease. All MBC patients exhibited a response to therapy. Median PFS was 6.2 months. Median OS was 15.0 months. Conclusion: The combination of eribulin at a dose of 1.4 mg/m2 with standard dose durvalumab had a favorable AE profile in patients with previously treated HER2− MBC and ROC. The early antitumor activity observed in all MBC patients enrolled in the study suggests that further investigation of this combination is warranted.
First Reported Case of a Pyrophosphate Kidney Stone in a Human
Authors: Gigax Michael R. , Yang Lee , Austin Glenn , Mandel Neil S. , Lulich Jody P. , Asplin John R.
Published: October 2023

Urolithiasis composed of pyrophosphate salts has only been reported in animals, in the form of potassium magnesium pyrophosphate. However, there have been no reports of pyrophosphate stones in humans. Hypophosphatasia is an inherited disease characterized by low alkaline phosphatase activity and elevated levels of pyrophosphate in blood and urine. Urolithiasis is a part of the hypophosphatasia phenotype. The role of elevated urine pyrophosphate levels in the formation of stones in hypophosphatasia is unknown. Here, we report a case of a 60-year-old man with recurrent urolithiasis. The patient’s most recent presentation was gross hematuria and his computed tomography scan showed bilateral kidney stones. Stones were removed via retrograde intrarenal surgery. Stone analysis revealed a composition of potassium magnesium pyrophosphate. The patient also has a long history of fracturing bone disease which led to the consideration of hypophosphatasia as the cause of both his bone disease and pyrophosphate stones. Hypophosphatasia was confirmed by genetic analysis. Pyrophosphate has been of interest in the fields of mineral metabolism because of its action as a crystallization inhibitor. However, pyrophosphate at elevated concentrations in the presence of divalent cations can exceed its solubility. Nephrocalcinosis and stone disease have been described in hypophosphatasia; stones have been assumed to be calcium phosphate but no compositional analysis has been reported. This is the first report of human stones composed of pyrophosphate salts, which led to the subsequent diagnosis of hypophosphatasia in this patient.