bluuebunny/crossref_metadata_2025 huggingface dataset:
Etiology and Ureteral Reconstruction Strategy for Iatrogenic Ureteral Injuries: A Retrospective Single-Center Experience
Authors: Ding Guangpu , Li Xinfei , Fang Dong , Hao Han , Li Xuesong , Zhou Liqun
Published: March 2021

Objective: To analyze the etiology, characteristics, and ureteral reconstruction strategies of iatrogenic ureteric injuries in a high-volume center. Methods: Between September 2010 and August 2019, we retrospectively collected patients who underwent ureteral reconstruction due to iatrogenic ureteric injuries. Patient profiles, laboratory data, imaging studies, perioperative data, and complications were recorded. Results: Sixty-eight patients were enrolled in this study. The upper, middle, and lower thirds of the ureter were affected in 30, 2, and 36 cases, respectively. Of the 68 ureteric injuries, 69.1% occurred during urological procedures, followed by gynecological procedures, general surgery, radiotherapy, and orthopedic surgery. The majority of urological injuries (41, 87.2%) occurred due to stone removal. There was a significant difference in the age, sex, and location of ureteric injuries between the urological and nonurological groups. The median follow-up time was 17.9 months. The overall symptom remission rate was 91.2% and ranged from 87.5 to 100% for different reconstructive surgeries. Conclusions: Urological procedures were the most common cause of iatrogenic ureteric injury; thus, extra care should be taken. Timely detection and appropriate treatment of the ureteric injuries are necessary. Treatment strategies should be depended on the location and length of injury.
Association of Race with In-Hospital and Post-Hospitalization Mortality in Patients with Acute Kidney Injury
Authors: Hassan Muzamil O. , Owoyemi Itunu , Abdel-Rahman Emaad M. , Ma Jennie Z. , Balogun Rasheed A.
Published: March 2021

Introduction: Acute kidney injury (AKI) is known to be associated with increased mortality, and racial differences in hospital mortality exist in patients with AKI. However, it remains to be seen whether racial differences exist in post-hospitalization mortality among AKI patients. Methods: We analyzed data of adult AKI patients admitted to the University of Virginia Medical Center between January 1, 2001, and December 31, 2015, to compare in-hospital and post-hospitalization mortality among hospitalized black and white patients with AKI. Multivariable logistic regression analysis was used to analyze the association between race and in-hospital mortality, and 90-day post-hospitalization mortality among AKI patients that were discharged. Kaplan-Meier survival curve was used to evaluate long-term survival between black and white patients. Results: Black patients had lower in-hospital mortality than white patients after adjusting for age, sex, estimated glomerular filtration rate, hospital length of stay, severity of AKI, comorbidities, and the need for dialysis and mechanical ventilation (odds ratio: 0.82; 95% confidence interval, 0.70–0.96, p = 0.0015). Similarly, at 90-day post-hospitalization, black patients had significantly lower adjusted odds of death than white patients (odds ratio: 0.64; 95% confidence interval, 0.46–0.93; p = 0.008). The median length of follow-up was 11.9 months (0.6–46.7 months). Kaplan-Meier survival curve showed that long-term survival was significantly better in black patients compared to white patients (median duration of survival; 39.7 vs. 24.8 months; p ≤ 0.001). Conclusions: Black patients with AKI had lower in-hospital mortality, 90-day post-hospitalization mortality, and better long-term survival rates compared to white patients with AKI.
RELA Fusion-Positive Ependymoma in a Child with Down Syndrome: A Case Report
Authors: Chan Julie L. , Kashanian Alon , Bannykh Serguei I. , Majlessipour Fataneh , Breunig Joshua J. , Danielpour Moise
Published: March 2021

Introduction: Down syndrome (DS) is the most common multiple malformation syndrome in humans and is associated with an increased risk of childhood malignancy, particularly leukemia. Incidence of brain tumors in patients with DS is limited to sporadic cases. We report the first case of a RELA fusion-positive ependymoma in a 3-year-old boy with DS. Case Presentation: Imaging prompted by new left-sided hemiparesis demonstrated an 8-cm hemorrhagic right temporal-parietal mass. Subsequent image-complete resection confirmed a RELA fusion-positive anaplastic ependymoma with 90% OLIG2 staining. Postoperatively, the patient, unfortunately, experienced fatal recurrence and drop metastases with leptomeningeal involvement. Conclusion: To our knowledge, this is the first reported case of a confirmed RELA fusion-positive ependymoma in a child with DS. We discuss this finding in the context of intracranial tumors in children with DS, as well as the finding of 90% positive OLIG2 expression and its potential as a prognostic marker.
Synchronous Partial Nephrectomy and Renal Artery Aneurysm Repair in Bilateral Renal Cancers: Case Report and Literature Review
Authors: Foschi Nazario , Ragonese Mauro , Russo Pierluigi , Nigro Domenico , Di Gianfrancesco Luca , Sica Simona , Tinelli Giovanni , Thsomba Yamume , Bassi PierFrancesco
Published: March 2021

The treatment of renal cancer has changed in the last decades with an increase in application of conservative surgery such as partial nephrectomy (PN) in order to achieve an optimal oncological outcome with the maximum preservation of renal function. The indication for PN is mandatory in case of bilateral tumors or in case of impaired renal function. Renal artery (RA) aneurysm (RAA) is a rare occurrence, and its treatment could be radiological or surgical according to the anatomy of the aneurysm and the clinical characteristics of the patients. Here, we report a case of simultaneous ipsilateral occurrence of renal cancer and RAA in a patient with bilateral renal masses, treated with 1 surgical procedure with good functional and oncological outcomes. This rare occurrence must be known by surgeons treating renal cancers, and it is possible to perform the 2 procedures in 1 surgical step.
Common Presentation of an Uncommon Small Intestinal Lymphoma: A Rare Case Entity
Authors: Bharti Sushma , Bharti Jyotsna Naresh , Lodha Mahendra
Published: March 2021

Primary gastrointestinal NHL accounts for 30–40% of all extranodal NHL. Primary gastrointestinal lymphomas constitute 5% of total gut neoplasms. Bowel perforation is a severe life-threatening complication and sometimes initial presentation of gastrointestinal lymphoma. A 60-year-old man presented with complaints of abdominal pain, distension, nausea and vomiting. There was clinical suspicion of acute intestinal perforation, which was confirmed by radiology. The patient underwent emergency laparotomy. The resected bowel on histopathological examination and immunohistochemistry was diagnosed as the high-grade transformation of follicular lymphoma (FL). The patient received 6 cycles of chemotherapy and is doing well at 3 years of follow-up. Herein, we report this rare malignancy of the small intestine. FL mostly presents as a nodal disease but also involves the extranodal sites. The most common site of primary gastrointestinal-follicular lymphoma (GI-FL) is the small intestine. The cellular and molecular characteristic of GI-FL is different from that of the nodal FL. Extranodal FL is usually localized, but the prognosis of transformed FL is low, and these are managed by surgery followed by chemotherapy. High clinical suspicion and extensive sampling of perforated bowel are essential to diagnose the high-grade transformation of FL.
Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells
Authors: Le Yichen , He Yi , Bai Meirong , Wang Ying , Wu Jiaxue , Yu Long
Published: March 2021

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.
Lupus Membranous Nephropathy
Authors: Ponticelli Claudio , Moroni Gabriella , Fornoni Alessia
Published: March 2021

Background: Lupus membranous nephropathy (LMN) is a rare disease, usually associated with nephrotic syndrome. Methods: We reviewed the literature by searching for the following terms on Pubmed.gov: lupus nephritis, membranous nephropathy (MN), lupus membranous nephropathy, nephrotic syndrome, and Class V lupus nephritis. Results: The histology of LMN at light microscopy is similar to that of primary MN. Cases of MN associated with focal or diffuse proliferation are not considered LMN by the International Society of Nephrology/Renal Pathology Society classification. Immunofluorescence study of LMN shows deposits of all immunoglobulins and complement. Tubulo-reticular structures, extraglomerular deposits, subepithelial, and scanty subendothelial deposits can be seen on electron microscopy. Phospholipase A2 receptor deposits are usually but not necessarily absent in LMN. The pathogenesis is still not completely understood. The inflammatory milieu of lupus may favor the development of autoantigens and intraglomerular assembly of immune complexes. These are more often associated with mesangial or endocapillary hypercellular lesions. Alternatively, autoantibodies may bind autoantigens in the glomerular subepithelium, triggering a signaling cascade leading to LMN. A central role in the development of podocyte injury and proteinuria is played by the components of complement C5b-C9. CKD progression in LMN is slow but may be accelerated by the frequency of renal flares. Persistent nephrotic syndrome and/or the frequent use of corticosteroids may lead to a series of life-threatening complications. Discussion: Treatment of arterial hypertension, dyslipidemia, and diabetes are of paramount importance. Besides specific therapies of these complications, hydroxychloroquine and vitamin D supplementation are recommended. Immunosuppression should be limited to patients with nephrotic proteinuria. The most frequently used drugs are corticosteroids, calcineurin inhibitors, cyclophosphamide, mycophenolate, and rituximab, alone or combined. Early detection and treatment of renal flares is of paramount importance to prevent CKD progression.
Minimizing Intracochlear Pressure: Influence of the Insertion Sheath
Authors: Ucta Ceyhun , Mittmann Philipp , Ernst Arneborg , Seidl Rainer , Lauer Gina
Published: March 2021

Objective: Atraumatic cochlear implantation (CI) and insertion of the electrode in particular are major goals of recent CI surgery. Perimodiolar electrode arrays need a stylet or exosheath for insertion. The sheath can influence the intracochlear pressure changes during insertion of the electrode. The aim of this study was to modify the insertion sheath to optimize intracochlear pressure changes. Methods: In an artifical cochlear model, 7 different modified insertion sheaths were used. The intracochlear pressure was measured with a micro-optical sensor in the apical part of the model cochlea. Results: Significant lower intracochlear pressure changes were observed when the apical part of the insertion sheath was either shortened or tapered. Modification of the stopper does influence the intracochlear pressure significantly. Conclusion: Modification of the insertion sheath leads to lower intracochlear pressure gain. The differences and impact on intracochlear pressure changes found in this study underline the importance of even subtle modifications of the electrode insertion technique.
Bridging Therapy and Occlusion Site Influence Symptomatic Hemorrhage Rate after Thrombectomy: A Daily Practice Study in 623 Stroke Patients
Authors: Cabrera-Maqueda Jose María , Alba-Isasi Maria Teresa , Díaz-Pérez Jose , Albert-Lacal Laura , Morales Ana , Parrilla Guillermo
Published: March 2021

Background: Comparison of symptomatic intracranial hemorrhage (SICH) rates between stroke patients treated with bridging therapy (BT) and primary mechanical thrombectomy (PMT) are scarce and difficult to interpret due to baseline differences between both populations. Methods: Retrospective analysis of patients with acute ischemic stroke treated with endovascular therapy (BT or PMT) was performed at our center between January 2010 and June 2017. Results: Six hundred twenty-three patients were included. Global SICH rate was 9% overall: 6.8% in the PMT group and 12.6% in the BT group. The following factors significantly associated with SICH after multivariate analysis: MCA occlusion (p: 0.047), stroke of unknown origin (p: 0.025), BT (p: 0.024), and procedural time over 65 min (p: 0.027). The following variables presented a statistically significant higher frequency in patients treated with PMT: atrial fibrillation (p: 0.005), anticoagulant medication (p < 0.001), wake-up strokes (p < 0.001), atherothrombotic etiology (p < 0.05), combined thrombectomy technique (p: 0.008), longer procedural times (p: 0.025), and favorable outcome at 3 months (p: 0.011). The following variables presented a statistically significant higher frequency in patients treated with BT: antiplatelet medication (p: 0.048), MCA occlusions (p: 0.017), cardioembolic etiology (p < 0.05), stent retriever/aspiration technique (p: 0.008), and SICH (p: 0.013). Patients with MCA occlusions had twice the risk of SICH after BT than after PMT (16.4 and 8.6%, p: 0.038). Conclusions: In this clinical series, the SICH rate was higher in patients treated with BT than in those treated with PMT. Relevant differences in baseline (related to IVT contraindications) were found between both groups. Randomized studies of BT versus PMT in populations with similar baseline characteristics might be of interest.
Clinical and Molecular Cytogenetic Characteristics of Five Cases with Isodicentric Y Chromosome
Authors: Manotas María C. , García-Acero Mary , González Daniel M. , Moreno Olga M. , Suárez-Obando Fernando , Céspedes Camila , Forero Catalina , Pérez Jaime , Fernández Nicolás , Rojas Adriana
Published: March 2021

Isodicentric Y chromosome [idic(Y)] is one of the most common structural abnormalities of the Y chromosome and has been observed in patients with reproductive disorders and in patients with disorders of sexual development. Most idic(Y) chromosomes are found in mosaic form with a 45,X cell line. These chromosomes are highly unstable during mitosis due to the presence of 2 centromers, which explains their probable loss in early mitosis or mitosis of the embryo and therefore the presence of the 45,X line. It has been hypothesized that the proportion of 45,X cells in various tissues probably influences the phenotypic sex of individuals carrying an idic(Y) chromosome, ranging from infertile men, hypospadias, ambiguous genitalia, and Turner syndrome to sex reversal. In this article we present 5 cases of patients with idic(Y) referred for suspected disorder of sex development (DSD), 3 with a male assignment and 2 with a female assignment. All cases have variable clinical characteristics, which were assessed by the transdisciplinary group of Disorders of Sex Development of the Hospital Universitario San Ignacio, Bogotá, Colombia. Patients were analyzed by conventional and molecular cytogenetics using high-resolution G-band and FISH techniques. Our findings highlight the importance of cytogenetic studies in the diagnosis of DSD patients.
Morphological Differences between Liquid-Based Cytology and Conventional Preparation in Endometrial Endometrioid Carcinoma Grade 1 and Grade 3, and the Differentiation of Grades in Each Method
Authors: Odashima Hirokazu , Yoshioka Haruhiko , Ota Kasumi , Goto Yuya , Noro Misuzu , Horie Kayo , Watanabe Jun
Published: March 2021

Introduction: Direct smearing preparation (conventional preparation [CP]) has been widely used for endometrial cytology in Japan. In CP, sampling and screening errors are problematic. In liquid-based cytology preparation (LBC), the problems of CP can be solved. But there is a problem that cytological findings of LBC are different from those of CP. The purpose of this study was to evaluate the differences of morphological findings of endometrial cytology between LBC and CP, and the usefulness of the endometrial LBC to differentiate endometrioid carcinoma grade 1 (G1) from grade 3 (G3). Methods: Thirteen cases of endometrioid carcinoma G1, and 5 cases of G3 collected by the Softcyte device and prepared by LBC and CP (split specimen) were used. We focused on the following items: (1) the number of clusters per cm2, (2) the number of layers of clusters, (3) area of clusters, (4) perimeter of clusters, (5) roundness of clusters, (6) complexity of clusters, (7) area of nucleus, (8) perimeter of nucleus, (9) roundness of nucleus, (10) complexity of nucleus, (11) area of nucleolus, and (12) nucleolus-nucleus ratio (N/N). Results: Compared with CP, the number of clusters and layers of the clusters in LBC were significantly larger in G1. The area and perimeters of the clusters and the nucleus were significant smaller, and the N/N ratio was greater in LBC than that in CP in both G1 and G3. Regarding morphological differences between G1 and G3 in LBC and CP, the number of layers was significantly larger in G1 than in G3 in LBC and CP. The area of the clusters in LBC was significantly larger in G1 than in G3. The area and perimeters of the nucleus in CP and the area of the nucleolus and N/N ratio in LBC and CP were significantly smaller in G1 than in G3. Conclusion: In the endometrial cytology, it became clear that the cell image was different between LBC and CP and between G1 and G3. By microscopic examination understanding the characteristics of the cell image in LBC, endometrial LBC could be useful to diagnose endometrial carcinoma.
Evolution of Sex Chromosome Heteromorphy in Geographic Populations of the Japanese Tago’s Brown Frog Complex
Authors: Kuwana Chiao , Fujita Hiroyuki , Tagami Masataka , Matsuo Takanori , Miura Ikuo
Published: March 2021

The sex chromosomes of most anuran amphibians are characterized by homomorphy in both sexes, and evolution to heteromorphy rarely occurs at the species or geographic population level. Here, we report sex chromosome heteromorphy in geographic populations of the Japanese Tago’s brown frog complex (2n = 26), comprising Rana sakuraii and R. tagoi. The sex chromosomes of R. sakuraii from the populations in western Japan were homomorphic in both sexes, whereas chromosome 7 from the populations in eastern Japan were heteromorphic in males. Chromosome 7 of R. tagoi, which is distributed close to R. sakuraii in eastern Japan, was highly similar in morphology to the Y chromosome of R. sakuraii. Based on this and on mitochondrial gene sequence analysis, we hypothesize that in the R. sakuraii populations from eastern Japan the XY heteromorphic sex chromosome system was established by the introduction of chromosome 7 from R. tagoi via interspecies hybridization. In contrast, chromosome 13 of R. tagoi from the 2 large islands in western Japan, Shikoku and Kyushu, showed a heteromorphic pattern of constitutive heterochromatin distribution in males, while this pattern was homomorphic in females. Our study reveals that sex chromosome heteromorphy evolved independently at the geographic lineage level in this species complex.
How Do We Manage Hematopoietic Cell Transplant during the SARS-CoV-2 Pandemic?
Authors: Xiao Haowen , Luo Yi , Shi Jimin , Jin Aiyun , Mohty Mohamad , Nagler Arnon , Gale Robert Peter , Huang He
Published: March 2021

Patients receiving a hematopoietic cell transplant are thought to be at increased risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus infectious disease 2019. Transplant activities at our center continue, and notably, no patient has been infected with SARS-CoV-2. Indeed, social distancing, masking, and education for patients and donors are major pillars of prevention. We recommend potential transplant recipients and donors to be tested for SARS-CoV-2 with qRT-PCR, serum antibody detection, and a lung CT scan pretransplant. If possible, stem cells from HLA-matched unrelated donors by local processing laboratories should be cryopreserved and shipped before initiating pretransplant conditioning. An alternative HLA-haplotype-matched related donor should be identified and evaluated as a backup. The interval immediately after discharge is the time of greatest risk for SARS-CoV-2 infection because of travel and exposure to infected persons. We recommend self-isolation and minimal contact with family members. Nonessential clinic visits should be deferred or substituted with telemedicine consultations if possible. These recommendations are based on our experience at a major transplant center in China. Although some recommendations are evidence based, other recommendations are not and warrant validation in controlled trials.
The H2020 “NoHoW Project”: A Position Statement on Behavioural Approaches to Longer-Term Weight Management
Authors: Stubbs R. James , Duarte Cristiana , O’Driscoll Ruairi , Turicchi Jake , Kwasnicka Dominika , Sniehotta Falko F. , Marques Marta M. , Horgan Graham , Larsen Sofus , Palmeira António , Santos Inês , Teixeira Pedro J. , Halford Jason , Heitmann Berit Lilienthal ,   The EASO Obesity Management Task Force
Published: March 2021

There is substantial evidence documenting the effects of behavioural interventions on weight loss (WL). However, behavioural approaches to initial WL are followed by some degree of longer-term weight regain, and large trials focusing on evidence-based approaches to weight loss maintenance (WLM) have generally only demonstrated small beneficial effects. The current state-of-the-art in behavioural interventions for WL and WLM raises questions of (i) how we define the relationship between WL and WLM, (ii) how energy balance (EB) systems respond to WL and influence behaviours that primarily drive weight regain, (iii) how intervention content, mode of delivery and intensity should be targeted to keep weight off, (iv) which mechanisms of action in complex interventions may prevent weight regain and (v) how to design studies and interventions to maximise effective longer-term weight management. In considering these issues a writing team within the NoHoW Consortium was convened to elaborate a position statement, and behaviour change and obesity experts were invited to discuss these positions and to refine them. At present the evidence suggests that developing the skills to self-manage EB behaviours leads to more effective WLM. However, the effects of behaviour change interventions for WL and WLM are still relatively modest and our understanding of the factors that disrupt and undermine self-management of eating and physical activity is limited. These factors include physiological resistance to weight loss, gradual compensatory changes in eating and physical activity and reactive processes related to stress, emotions, rewards and desires that meet psychological needs. Better matching of evidence-based intervention content to quantitatively tracked EB behaviours and the specific needs of individuals may improve outcomes. Improving objective longitudinal tracking of energy intake and energy expenditure over time would provide a quantitative framework in which to understand the dynamics of behaviour change, mechanisms of action of behaviour change interventions and user engagement with intervention components to potentially improve weight management intervention design and evaluation.
A New Variant B Chromosome in Auchenipteridae: The Role of (GATA)n and (TTAGGG)n Sequences in Understanding the Evolution of Supernumeraries in Trachelyopterus
Authors: Felicetti Denise , Haerter Chrystian A.G. , Baumgärtner Lucas , Paiz Leonardo M. , Takagui Fábio H. , Margarido Vladimir P. , Blanco Daniel R. , Feldberg Eliana , da Silva Maelin , Lui Roberto L.
Published: March 2021

Basic and molecular cytogenetic techniques were carried out in 3 Neotropical region populations of catfishes, two of Trachelyopterus galeatus (one from the marshlands of Paraguay River basin and another from Lago Catalão, Amazon River basin) and one of Trachelyopterus porosus, a sympatric population to T. galeatus from the Amazon River basin. This study aimed to describe and understand the structure and evolution of Trachelyopterus B chromosomes, mainly through physical mapping of repetitive elements. A diploid number of 58 chromosomes was found for all individuals, as well as the presence of B chromosomes. For T. porosus this is the first report of a supernumerary. The sympatric species of T. galeatus and T. porosus from Amazon River had 1–3 B chromosomes and T. galeatus from Paraguay River had 1–2 B chromosomes, all of them showed intra- and interindividual numerical variation. Two females of T. porosus exhibited a new variant B chromosome (B2), previously not seen in Auchenipteridae, which might have originated from B1 chromosomes. All B chromosomes were entirely heterochromatic. In contrast to all complement A and B2 chromosomes, in which the telomeric sequences were found in the telomeric regions, B1 chromosomes of all populations were totally marked by (TTAGGG)n probes. (GATA)n sequence sites were found through all complement A chromosomes, but B1 and B2 chromosomes exhibited only a clustered block in one of the chromosome arms. The most frequent B chromosomes (B1) in all populations/species, including those previously studied in Auchenipteridae catfishes, share the following characteristics: totally heterochromatic, small, metacentric, with accumulation of repetitive (TTAGGG)n sequences, and a low number of (GATA)n copies, which might suggest a common ancient origin in Trachelyopterus species/populations.
Molecular Cytogenetic Characterization of the Murine Melanoma Cell Lines S91 Clone M3 and B16-F1 with Variant B16-4A5
Authors: Piaszinski Katja , Rincic Martina , Liehr Thomas , Azawi Shaymaa
Published: March 2021

Melanoma is considered to be one of the most aggressive human tumors. Thus, early molecular diagnosis with risk factor stratification could be an efficacious strategy to increase the survival rates in affected patients. Murine cell lines B16-F1, B16-4A5, and S91 clone M3 are the ones most commonly applied in melanoma research. However, genetic peculiarities of these 3 cell lines have not been studied in detail before. Here, we closed this gap by molecular cytogenetic and array-comparative genomic hybridization studies and the translation of the characterized imbalances into the human genome. This study revealed severely rearranged karyotypes with in parts similar imbalances for all 3 cell lines. Interestingly, they involve genes known to play major roles in human melanoma. These are specifically the oncogenes and tumor suppressor genes, being associated with aggressive forms of melanoma. B16-F1, B16-4A5, and S91 clone M3 revealed aberrations which were similarly observed in human eye and skin but not in human uveal melanoma. Thus, they can be considered as model systems for advanced eye and skin melanoma.
A Recurrent Variant in POLR1B, c.3007C>T; p.Arg1003Cys, Associated with Atresia of the External Canal and Microtia in Treacher Collins Syndrome Type 4
Authors: Enomoto Yumi , Tsurusaki Yoshinori , Tominaga Makiko , Kobayashi Shinji , Inoue Maki , Fujita Kazutoshi , Kumaki Tatsuro , Murakami Hiroaki , Kurosawa Kenji
Published: March 2021

Treacher Collins syndrome (TCS) is a heterogenous malformation syndrome characterized by a distinct facial appearance including downslanting palpebral fissures, malar hypoplasia, conductive hearing loss, and mandibular hypoplasia. Recently, a new causative gene, POLR1B, encoding DNA-directed RNA polymerase I subunit RPA2, was identified as a fourth type of TCS (TCS4). We describe another patient with TCS4 caused by a recurrent POLR1B variant, c.3007C>T; p.Arg1003Cys. Including our patient, all 4 patients with p.(Arg1003Cys) had atresia of the external auditory canal and microtia. All of the reported pathogenic variants in POLR1B were clustered at only 2 residues. Our patient highlights the genotype-phenotype correlation in TCS4 associated with POLR1B.
Tandem Repeat-Based Probes Support the Loop Model of Pericentromere Packing
Authors: Ivanova Nadezhda G. , Ostromyshenskii Dmitrii , Podgornaya Olga
Published: March 2021

Constitutive heterochromatin is the most mysterious part of the eukaryotic genome. It forms vital chromosome regions such as the centromeric and the pericentromeric ones. The main component of heterochromatic regions are tandem repeats (TR), and their specific organization complicates assembly, annotation, and mapping of these regions. Unannotated and unmapped TR arrays are still present in database contigs. In this study, we used a set of TR in the genomes of the pig (Sus scrofa) and the Chinese hamster (Cricetulus griseus) identified with the help of bioinformatics techniques and determined the specificity of the designed probes. The signal of the 4 pig TR probes in spermatogenic cells was often ring-shaped, especially in primary spermatocytes. The rings were located in the regions relatively weakly stained with DAPI. The unique assembly of the centromeric region was traced using the hamster meiotic chromosomes. The probe specific to chromosome 5 was used. Two signals, arranged as rings, were seen at the pachytene stage, similar to those in the pig spermatogenic cells. In the spermatogenic cells of both pig and hamster, the rings appeared on the chromosomes with pericentromeric TR probes. Our observations support the loop model of the centromeric region, the size of the loops being about 50 kb.
Interstitial Deletion of 2q22.2q22.3 Involving the Entire ZEB2 Gene in a Case of Mowat-Wilson Syndrome
Authors: Refaat Khaled , Helmy Nivine , Elawady Mohamed , El Ruby Mona , Kamel Alaa , Mekkawy Mona , Ashaat Engy , Eid Ola , Mohamed Amal , Rady Mervat
Published: March 2021

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by dysmorphic features, mental retardation, and congenital heart disease (CHD). MWS results from microdeletions of chromosome 2q23 or de novo SNVs involving the ZEB2 gene. Here, we report on an Egyptian MWS patient diagnosed by chromosomal microarray (CMA). A 1-year-old male child was referred to the CHD clinic, National Research Centre, presenting with dysmorphic features and CHD. The patient was referred to the human cytogenetics department for cytogenetic analysis and for screening of subtelomere rearrangements and microdeletion loci, using MLPA, and all revealed normal results. CMA revealed an interstitial 2.27-Mb microdeletion in chromosome 2q, involving the entire ZEB2 gene and other genes. This study emphasizes the significance of CMA in the detection of microdeletions/microduplications and as a screening tool in cases presenting with CHD and extracardiac manifestations. MWS should be suspected in patients presenting with the characteristic facial dysmorphism, developmental delay, seizures, Hirschsprung disease, and congenital heart anomalies, especially those involving the pulmonary arteries or pulmonary valves. It is recommended to include the ZEB2 locus in the MLPA microdeletions probes.
An Evaluation of Morphological Changes and Deformability of Suspended Red Blood Cells Prepared Using Whole Blood with Different Hemoglobin Levels of Tibetans
Authors: Zhong Rui , Han Dingding , Wu Xiaodong , Wang Hong , Li Wanjing , He Zeng , Zhang Xuejun , Liu Jiaxin
Published: March 2021

Background: The hypoxic environment stimulates the human body to increase the levels of hemoglobin (HGB) and hematocrit and the number of red blood cells. Such enhancements have individual differences, leading to a wide range of HGB in Tibetans’ whole blood (WB). Study Design: WB of male Tibetans was divided into 3 groups according to different HGB (i.e., A: >120 but ≤185 g/L, B: >185 but ≤210 g/L, and C: >210 g/L). Suspended red blood cells (SRBC) processed by collected WB and stored in standard conditions were examined aseptically on days 1, 14, 21, and 35 after storage. The routine biochemical indexes, deformability, cell morphology, and membrane proteins were tested. Results: Mean corpuscular volume, adenosine triphosphate, pH, and deformability were not different in group A vs. those in storage (p > 0.05). The increased rate of irreversible morphology of red blood cells was different among the 3 groups, but there was no difference in the percentage of red blood cells with an irreversible morphology after 35 days of storage. Group C performed better in terms of osmotic fragility and showed a lower rigid index than group A. Furthermore, SDS-PAGE revealed similar cross-linking degrees of cell membrane protein but the band 3 protein of group C seemed to experience weaker clustering than that of group A as detected by Western Blot analysis after 35 days of storage. Conclusions: There was no difference in deformability or morphological changes in the 3 groups over the 35 days of storage. High HGB levels of plateau SRBC did not accelerate the RBC change from a biconcave disc into a spherical shape and it did not cause a reduction in deformability during 35 days of preservation in bank conditions.
Guillain-Barre Syndrome following COVID-19 Infection: First Case Report from Kuwait and Review of the Literature
Authors: Kamel Walaa A. , Ibrahim Ismail Ismail , Al-Hashel Jasem Yousef
Published: March 2021

Objective: Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy that is often related to a previous infectious exposure. GBS emerged as a potentially serious complication of coronavirus disease 2019 (COVID-19) since its declaration as a global pandemic. We report the first case from Kuwait, to the best of our knowledge. Clinical Presentation: A 72-year-old male presented with 3 weeks history of acute progressive and ascending lower limbs weakness. He developed these symptoms 3 weeks after testing positive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Electrophysiological studies showed acute demyelinating polyradiculoneuropathy and cerebrospinal fluid showed protein-cell dissociation. He was successfully treated with intravenous immunoglobulins (IVIGs). Conclusion: Neurologists should be aware of GBS as a potentially serious complication associated with CO­VID-19. Our patient had a favorable outcome with IVIG with no autonomic or respiratory affection.
Applying the Exoscope to Lacrimal Surgery: Preliminary Experience
Authors: Pirola Francesca , De Virgilio Armando , Di Maria Alessandra , Russo Elena , Di Bari Matteo , Costantino Andrea , Ferreli Fabio , Mercante Giuseppe , Colombo Giovanni , Spriano Giuseppe , Malvezzi Luca
Published: March 2021

Purpose: The aim of the study was to investigate the role of the exoscope as an assisting tool in endoscopic dacryocystorhinostomy (e-DCR). Materials and Methods: In this observational retrospective study, the application of the VITOM® exoscope was studied in a group of 21 patients undergoing mono- or bilateral DCR. The primary endpoint was to evaluate resolution of symptoms (epiphora/dacryocystitis) at the 6-month follow-up and time for surgery. Qualitative features of the exoscope (intraoperative view of the surgical field) and comparison with the typical setting for DCR were analyzed as secondary endpoints. A questionnaire was administered to surgical team members (ENT surgeon, ophthalmologist, and scrub nurse) to evaluate the perceived quality of this new technology (12 items valued as “good” = 2, “acceptable” = 1, and “not acceptable” = 0). A questionnaire score of 24 out of 24 was valued as “completely approved,” score 20–23 as “moderately approved,” and score ≤19 as “weakly approved.” Patients were divided into 3 consecutive groups, and questionnaire scores by each team member were analyzed for tendencies. Statistical analysis was performed to test significance at p < 0.05. Local Ethical Committee approval was obtained. Results: No significant differences were found between exoscope-set DCR and classic setting for concerned patient outcomes (failure rate: 3.2 vs. 3.8%, respectively, p = 0.896) and mean time for surgery (20’ vs. 23’, respectively, p = 0.091). The exoscope was valued by surgical team members as “completely approved” in 55.5% of cases, “moderately approved” in 39.7%, and “weakly approved” in 4.8%. Questionnaire scores by the ENT, ophthalmologist, and scrub nurse showed an average increase in the 3 consecutive groups (p = 0.119, p = 0.024, and p < 0.001, respectively). Conclusions: The exoscope is a new tool that may support e-DCR. It has no effects on symptom outcomes (epiphora/dacryocystitis) and time for surgery compared to classic DCR. Based on self-perception, this new technology was accepted by all team members.
Elective Fetal Reduction in Dichorionic Diamniotic Twin Pregnancies on Parental Request: A Single-Centre Experience
Authors: Kaul Anita , Prasad Smriti , Anand Keerthana , Arora Saloni , Sharma Akshatha
Published: March 2021

Objectives: Our study aimed to examine a subset of electively reduced twins and compare their outcomes with those of expectantly managed twins, along with a cohort of singleton pregnancies. The secondary aim was to ascertain the procedure-related miscarriage risks. Methods: A retrospective cohort analysis was performed at Apollo Centre for Fetal Medicine, New Delhi, comparing pregnancy outcomes in dichorionic diamniotic twin pregnancies which were reduced to singletons (group 1) with that of women with dichorionic twins managed expectantly (group 0) and women with a singleton pregnancy (group 2). Comparison of continuous and categorical variables was conducted using standard statistical tests. Results: We analysed 35 twins which were reduced to singletons, 421 expectantly managed dichorionic twins and 1915 women with a singleton pregnancy. In the reduction group, the rate of procedure related pregnancy loss<24 weeks was lower, compared to the expectantly managed twins, although the difference was not statistically significant (5.71% [2/35] vs. 7.13% [30/421]; p = 1.000). The median gestational age at delivery was significantly higher in reduced twins compared to expectantly managed twin pregnancies (38.0 vs. 35.4 weeks respectively, p < 0.001) with a higher mean birth weight at delivery, both of which were comparable to that among the singleton pregnancies (38.3 weeks). The rates of preterm birth <32 weeks and <34 weeks in the expectantly managed twins were significantly higher at 19.8% (66/334) and 25.7% (86/334) compared to the reduced twins, all of whom delivered beyond 34 weeks. The rates of preterm births <32 weeks, <34 weeks, and the late preterm births in the reduced twins were comparable to those in the singleton cohort. Conclusions: The obstetric and perinatal outcomes after reduction of a dichorionic twin are better than an expectantly managed twin without an associated increase in pregnancy loss rates. Fetal reduction of dichorionic twin to a singleton appears to be a safe procedure in expert hands.
Evaluation of Patients with Delayed Endolymphatic Hydrops by Videonystagmography, Vestibular-Evoked Myogenic Potentials, and Electrocochleography
Authors: Yazdani Nasrin , Rahmaty Benyamin , Mousavi Meead , Aghazadeh Kayvan , Dabiri Sasan , Erfanian Reza , Jafari Neda , Rezazadeh Nima , Tajdini Ardavan , Givzadeh Hamed
Published: March 2021

Introduction: The categorization of delayed endolymphatic hydrops (DEH) based on the ear which produces vertigo may sometimes cause misdiagnosis. Objectives: The aim of this study was investigating the vestibular-evoked myogenic potentials (VEMPs), electrocochleography (ECoG), and videonystagmography (VNG) in cases with DEH to determine the ear that originates symptoms. Methods: In this cross-sectional study, 34 patients – 20 males and 14 females – with profound unilateral sensorineural deafness and vertigo attacks were recruited and evaluated by the ECoG, VNG, and VEMPs tests. Results: The average age was around 43; the summating potential/action potential was abnormal in 29.4% of patients in their normal auditive ear. In 32.4, 17.6, and 50% of cases with a deaf ear, absent, normal, and abnormal VEMPs results were sequentially observed, respectively. In normal-hearing ears, absent, normal, and abnormal VEMPs were observed in 23.5, 50, and 26.5%, respectively. In the normal-hearing ear, the distribution of abnormal VEMPs was 26.5%, and in the deaf ear, this parameter was abnormal in 50% of the opposite ear (p value = 0.00021). In the VNG test, among patients with a normal-hearing ear, results in 27 and 7 patients were sequentially normal and hypofunction. Conclusion and Significance: The probability of a hypofunction VNG test in a normal-hearing ear might be greater when the VEMPs results of the contralateral deaf ear are normal. In patients with a normal-hearing ear, the distribution of abnormal VEMPs in the contralateral deaf ear is greater, although the intact side may also manifest abnormality in VEMPs tests. The initial evaluation should begin in a deaf ear as well as for the normal-hearing ear ere utilizing ablation surgery.
The CHEK2*1100delC Mutation and Adolescent Breast Cancer: A Case Report of Breast Cancer in a 19-Year-Old and a Review of the Literature
Authors: Soleimani Tahereh , Engwall Abigail J. , Bourdon Corrie , Torabi Mohammad A. , Fortes Thais
Published: March 2021

Background: Breast cancer (BC) is the most common non-skin cancer affecting women but is extremely uncommon in the adolescent population. Genetic inheritance has been linked to <10% of BCs. CHEK2 is an uncommon genetic variant with a reported incidence of 0.3–1.6% in the general population and 4.9–5.7% in those with a family history of BC. Commonly, this mutation presents in females of European descent and is rare in North America. Case Presentation: A 19-year-old Caucasian female presented with breast pain and mass. She had an extensive family history of cancer, as well as a known CHEK2 gene mutation in 2 of her paternal aunts. Ultrasound and MRI confirmed a 4.5-cm mass with an enlarged right axillary lymph node. Image guided biopsy of the breast mass showed ER/PR-positive grade 1 invasive mucinous ductal cancer. Genetic testing confirmed an isolated CHEK2 mutation. After discussion by a multidisciplinary tumor board, the patient deferred bilateral mastectomy and underwent a right mastectomy with sentinel-lymph-node biopsy and immediate tissue-expander reconstruction. Final pathology confirmed ER/PR-positive Stage 1A (pT2 pN0 M0) invasive mucinous carcinoma. Chemotherapy was not recommended. Summary: Malignant adolescent breast masses are relatively rare and CHEK2 does not typically present at younger than 20 years of age. While there are many different differential diagnoses when evaluating an adolescent with a breast mass, we wish to increase providers’ suspicion of malignancy, specifically in those individuals who have a strong family history of BC and the CHEK2*1100delC mutation.
Analysis of Ascites-Challenged Blood in Patients with Liver Cirrhosis Using Rotational Thromboelastometry: How Robust Is the Evidence on Ascites-Attributed Fibrinolysis?
Authors: Bedreli Sotiria , Eleftheriadis Dimitrios , Jahn Michael , Canbay Ali , Saner Fuat , Katsounas Antonios
Published: March 2021

Introduction: For over 30 years, ascites has been postulated to facilitate fibrinolysis in patients with liver cirrhosis. In contrast to previous research employing conventional coagulation tests, this study aimed to characterize hemostatic interactions between blood and ascites using the rotational thromboelastometry (ROTEM). Methods: Blood samples – pure or mixed with ascites in a ratio of 1:1 – from cirrhotic patients (n = 10) were subjected to ROTEM analysis. In addition, a negative control group was built with cirrhotic patients (n = 10) whose blood was mixed with physiologic sodium chloride (0.9% NaCl) solution in a ratio of 1:1. Subsequently, ROTEM measurements were subjected to statistical analysis. Results: During ascites challenge, clotting time (CT, measured in seconds) was significantly prolonged in EXTEM (blood: 70.40 ± 20.40 vs. ascites/blood: 109.8 ± 47.7) and APTEM (blood: 66.50 ± 14.55 vs. ascites/blood: 138.7 ± 105.8), likely reflecting a dilution effect. However, CT in INTEM remained unchanged, suggesting a sustained intrinsic pathway function. Maximal clot firmness (measured in millimeters) in FIBTEM decreased significantly (blood: 14.70 ± 9.55 vs. ascites/blood: 6.00 ± 5.66), thus indicating depletion of fibrinogen in ascites. Strikingly, maximum lysis (measured in %) significantly decreased in EXTEM (blood: 9.30 ± 2.79 vs. ascites/blood: 5.50 ± 2.84), APTEM (blood: 8.50 ± 3.10 vs. ascites/blood: 5.60 ± 2.88), and INTEM (blood: 7.50 ± 2.27 vs. ascites/blood: 5.10 ± 3.48). Conclusions: ROTEM provided new evidence that ascites may not primarily induce fibrinolysis in cirrhotic patients. This finding seems to be of significant importance for the clinical management of cirrhotic patients experiencing complications, for example, abdominal hemorrhage after liver biopsy or paracentesis; here, replacement of prothrombin complex concentrates and/or fibrinogen concentrates may prove more beneficial than the use of fresh frozen plasma or antifibrinolytic drugs.
Late Recovery of Parathyroid Function after Total Thyroidectomy in Children and Adults: Is There a Difference?
Authors: de Jong Mechteld C. , Lorente-Poch Leyre , Sancho-Insenser Joan , Rozalén García Virginia , Brain Caroline , Abdel-Aziz Tarek E. , Hewitt Richard J. , Butler Colin R. , Sitges-Serra Antonio , Kurzawinski Tom R.
Published: March 2021

Background: Parathyroid failure after total thyroidectomy is the commonest adverse event amongst both children and adults. The phenomenon of late recovery of parathyroid function, especially in young patients with persistent hypoparathyroidism, is not well understood. This study investigated differences in rates of parathyroid recovery in children and adults and factors influencing this. Methods: A joint dual-centre database of patients who underwent a total thyroidectomy between 1998 and 2018 was searched for patients with persistent hypoparathyroidism, defined as dependence on oral calcium and vitamin D supplementation at 6 months. Demographic, surgical, pathological, and biochemical data were collected and analysed. Parathyroid Glands Remaining in Situ (PGRIS) score was calculated. Results: Out of 960 patients who had total thyroidectomy, 94 (9.8%) had persistent hypoparathyroidism at 6 months, 23 (24.5%) children with a median [range] age 10 [0–17], and 71 (75.5%) adults aged 55 [25–82] years, respectively. Both groups were comparable regarding sex, indication, extent of surgery, and PGRIS score. After a median follow-up of 20 months, the parathyroid recovery rate was identical for children and adults (11 [47.8%] vs. 34 [47.9%]; p = 0.92). Sex, extent, and indication for surgery had no effect on recovery (all p > 0.05). PGRIS score = 4 (HR = 0.48) and serum calcium >2.25 mmol/L (HR = 0.24) at 1 month were associated with a decreased risk of persistent hypoparathyroidism on multivariate analysis (p < 0.05). Conclusion: Almost half of patients recovered from persistent hypoparathyroidism after 6 months; therefore, the term persistent instead of permanent hypoparathyroidism should be used. Recovery rates of parathyroid function in children and adults were similar. Regardless of age, predictive factors for recovery were PGRIS score = 4 and a serum calcium >2.25 mmol/L at 1 month.