bims-bicyki 2023-01-15 papers

bims-bicyki

Biomed News

on Bicaudal-C1 and interactors in cystic kidney disease

Issue of 2023‒01‒15
fourteen papers selected by
Céline Gagnieux
École Polytechnique Fédérale de Lausanne (EPFL)

Pleural Effusions on MRI in Autosomal Dominant Polycystic Kidney Disease.
Cyst Fraction as a Biomarker in Autosomal Dominant Polycystic Kidney Disease.
Peripheral and central control of obesity by primary cilia.
TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?
Mechanism of cystogenesis by Cd79a-driven, conditional mTOR activation in developing mouse nephrons.
Brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood-cerebrospinal fluid barriers.
The Male Mouse Meiotic Cilium Emanates from the Mother Centriole at Zygotene Prior to Centrosome Duplication.
Evaluating the Safety and effectivenesS in adult KorEaN patients treated with Tolvaptan for management of autosomal domInAnt poLycystic kidney disease (ESSENTIAL): short-term outcomes during the titration period.
Polycystin-1 Is a Crucial Regulator of BIN1 Expression and T-Tubule Remodeling Associated with the Development of Dilated Cardiomyopathy.
Suspected Autosomal Recessive Polycystic Kidney Disease but Cerebellar Vermis Hypoplasia, Oligophrenia Ataxia, Coloboma, and Hepatic Fibrosis (COACH) Syndrome in Retrospect, A Delayed Diagnosis Aided by Genotyping and Reverse Phenotyping: A Case Report and A Review of the Literature.
Basal body organization and cell geometry during the cell cycle in Tetrahymena thermophila.
Multiple interactions of the dynein-2 complex with the IFT-B complex are required for effective IFT.
Validation of a semi-automatic method to measure total liver volumes in polycystic liver disease on computed tomography - high speed and accuracy.
Novel SPEF2 Variant in a Japanese Patient with Primary Ciliary Dyskinesia: A Case Report and Literature Review.

J Clin Med. 2023 Jan 03. pii: 386. [Epub ahead of print]12(1):

Pleural Effusions on MRI in Autosomal Dominant Polycystic Kidney Disease.

Jin Liu, Xiaorui Yin, Hreedi Dev, Xianfu Luo, Jon D Blumenfeld, Hanna Rennert, Martin R Prince.

  Autosomal dominant polycystic kidney disease (ADPKD) has cystic fluid accumulations in the kidneys, liver, pancreas, arachnoid spaces as well as non-cystic fluid accumulations including pericardial effusions, dural ectasia and free fluid in the male pelvis. Here, we investigate the possible association of ADPKD with pleural effusion. ADPKD subjects (n = 268) and age-gender matched controls without ADPKD (n = 268) undergoing body magnetic resonance imaging from mid-thorax down into the pelvis were independently evaluated for pleural effusion by 3 blinded expert observers. Subjects with conditions associated with pleural effusion were excluded from both populations. Clinical and laboratory data as well as kidney, liver and spleen volume, pleural fluid volume, free pelvic fluid and polycystic kidney disease genotype were evaluated. Pleural effusions were observed in 56 of 268 (21%) ADPKD subjects compared with 21 of 268 (8%) in controls (p < 0.0001). In a subpopulation controlling for renal function by matching estimated glomerular filtration rate (eGFR), 28 of 110 (25%) ADPKD subjects had pleural effusions compared to 5 of 110 (5%) controls (p < 0.001). Pleural effusions in ADPKD subjects were more prevalent in females (37/141; 26%) than males (19/127,15%; p = 0.02) and in males were weakly correlated with the presence of free pelvic fluid (r = 0.24, p = 0.02). ADPKD subjects with pleural effusions were younger (48 ± 14 years old vs. 43 ± 14 years old) and weighed less (77 vs. 70 kg; p ≤ 0.02) than those without pleural effusions. For ADPKD subjects with pleural effusions, the mean volume of fluid layering dependently in the posterior-inferior thorax was 19 mL and was not considered to be clinically significant. Pleural effusion is associated with ADPKD, but its role in the pathogenesis of ADPKD requires further evaluation.

Keywords:  ADPKD; MRI; T2; age; pleural fluid

DOI:  https://doi.org/10.3390/jcm12010386
J Clin Med. 2022 Dec 31. pii: 326. [Epub ahead of print]12(1):

Cyst Fraction as a Biomarker in Autosomal Dominant Polycystic Kidney Disease.

Larina A Karner, Sita Arjune, Polina Todorova, David Maintz, Franziska Grundmann, Thorsten Persigehl, Roman-Ulrich Müller.

  Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease. Patients at high risk of severe disease progression should be identified early in order to intervene with supportive and therapeutic measures. However, the glomerular filtration rate (GFR) may remain within normal limits for decades until decline begins, making it a late indicator of rapid progression. Kidney volumetry is frequently used in clinical practice to allow for an assessment of disease severity. Due to limited prognostic accuracy, additional imaging markers are of high interest to improve outcome prediction in ADPKD, but data from clinical cohorts are still limited. In this study, we examined cyst fraction as one of these parameters in a cohort of 142 ADPKD patients. A subset of 61 patients received MRIs in two consecutive years to assess longitudinal changes. All MRIs were analyzed by segmentation and volumetry of the kidneys followed by determination of cyst fraction. As expected, both total kidney volume (TKV) and cyst fraction correlated with estimated GFR (eGFR), but cyst fraction showed a higher R2 in a univariate linear regression. Besides, only cyst fraction remained statistically significant in a multiple linear regression including both htTKV and cyst fraction to predict eGFR. Consequently, this study underlines the potential of cyst fraction in ADPKD and encourages prospective clinical trials examining its predictive value in combination with other biomarkers to predict future eGFR decline.

Keywords:  ADPKD; MRI; cyst fraction

DOI:  https://doi.org/10.3390/jcm12010326
J Genet Genomics. 2023 Jan 09. pii: S1673-8527(23)00001-2. [Epub ahead of print]

Peripheral and central control of obesity by primary cilia.

Yue Wu, Jun Zhou, Yunfan Yang.

  Primary cilia are hair-like structures that protrude from the cell surface. They are capable of sensing external cues and conveying a vast array of signals into cells to regulate a variety of physiological activities. Mutations in cilium-associated genes are linked to a group of diseases with overlapping clinical manifestations, collectively known as ciliopathies. A significant proportion of human ciliopathy cases are accompanied by metabolic disorders such as obesity and type 2 diabetes. Nevertheless, the mechanisms through which dysfunction of primary cilia contributes to obesity are complex. In this article, we present an overview of primary cilia and highlight obesity-related ciliopathies. We also discuss the potential role of primary cilia in peripheral organs, with a focus on adipose tissues. In addition, we emphasize the significance of primary cilia in the central regulation of obesity, especially the involvement of ciliary signaling in the hypothalamic control of feeding behavior. This article therefore proposes a framework of both peripheral and central regulation of obesity by primary cilia, which may benefit further exploration of the ciliary role in metabolic regulation.

Keywords:  Adipogenesis; Adipose tissue; Ciliopathy; Hypothalamus; Metabolism

DOI:  https://doi.org/10.1016/j.jgg.2022.12.006
Int J Mol Sci. 2022 Dec 22. pii: 181. [Epub ahead of print]24(1):

TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?

Colya N Englisch, Friedrich Paulsen, Thomas Tschernig.

  The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6. TRPC3 plays a key role in Ca2+ homeostasis and is involved in transcellular Ca2+ reabsorption in the proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the PKD2 gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to better understand certain renal disorders and ultimately create new therapeutic targets to improve patient care.

Keywords:  TRPC3; TRPC6; autosomal dominant polycystic kidney disease; ischemic injury; kidney; renal carcinoma; renal tubular system; transient receptor potential

DOI:  https://doi.org/10.3390/ijms24010181
Sci Rep. 2023 Jan 10. 13(1): 508

Mechanism of cystogenesis by Cd79a-driven, conditional mTOR activation in developing mouse nephrons.

Linh Tran Nguyen Truc, Satoshi Matsuda, Akiko Takenouchi, Quynh Tran Thuy Huong, Yui Kotani, Tatsuhiko Miyazaki, Hiroaki Kanda, Katsuhiko Yoshizawa, Hiroyasu Tsukaguchi.

Polycystic kidney disease (PKD) is a common genetic disorder arising from developmental and postnatal processes. Defects in primary cilia and their signaling (eg, mTOR) underlie the pathogenesis. However, how mTOR regulates tubular integrity remains unclear. The paucity of faithful models has limited our understanding of pathogenesis and, therefore, the refinement of therapeutic targets. To understand the role of mTOR in early cystogenesis, we studied an in-house mouse model, Cd79a-Cre;Tsc1ff. (Cd79a-Tsc1 KO hereafter), recapitulating human autosomal-dominant PKD histology. Cre-mediated Tsc1 depletion driven by the promoter for Cd79a, a known B-cell receptor, activated mTORC1 exclusively along the distal nephron from embryonic day 16 onward. Cysts appeared in the distal nephron at 1 weeks of age and mice developed definite PKD by 4 weeks. Cd79a-Tsc1 KO tubule cells proliferated at a rate comparable to controls after birth but continued to divide even after postnatal day 14 when tubulogenesis is normally completed. Apoptosis occurred only after 9 weeks. During postnatal days 7-11, pre-cystic Cd79a-Tsc1 KO tubule cells showed cilia elongation, aberrant cell intercalation, and mitotic division, suggesting that defective cell planar polarity (PCP) may underlie cystogenesis. mTORC1 was activated in a portion of cyst-lining cells and occasionally even when Tsc1 was not depleted, implying a non-autonomous mechanism. Our results indicate that mTORC1 overactivation in developing distal tubules impairs their postnatal narrowing by disrupting morphogenesis, which orients an actively proliferating cell toward the elongating axis. The interplay between mTOR and cilium signaling, which coordinate cell proliferation with PCP, may be essential for cystogenesis.

DOI: https://doi.org/10.1038/s41598-023-27766-2
Brain Pathol. 2023 Jan 09. e13148

Brain heterotopia formation by ciliopathic breakdown of neuroepithelial and blood-cerebrospinal fluid barriers.

Hyun Jin Jung, Seungeun Yeo, Jaemyung Jang, Samuel Pleasure, Youngshik Choe.

  The developmental functions of primary cilia and the downstream signaling pathways have been widely studied; however, the roles of primary cilia in the developing neurovascular system are not clearly understood. In this study, we found that ablation of genes encoding ciliary transport proteins such as intraflagellar transport homolog 88 (Ift88) and kinesin family member 3a (Kif3a) in cortical radial progenitors led to periventricular heterotopia during late mouse embryogenesis. Conditional mutation of primary cilia unexpectedly caused breakdown of both the neuroepithelial lining and the blood-choroid plexus barrier. Choroidal leakage was partially caused by enlargement of the choroid plexus in the cilia mutants. We found that the choroid plexus expressed platelet-derived growth factor A (Pdgf-A) and that Pdgf-A expression was ectopically increased in cilia-mutant embryos. Cortices obtained from embryos in utero electroporated with Pdgfa mimicked periventricular heterotopic nodules of the cilia mutant. These results suggest that defective ciliogenesis in both cortical progenitors and the choroid plexus leads to breakdown of cortical and choroidal barriers causing forebrain neuronal dysplasia, which may be related to developmental cortical malformation.

Keywords:  Pdgfa; blood-brain barrier; brain heterotopia; choroid plexus; oligodendrocyte progenitors; primary cilia

DOI:  https://doi.org/10.1111/bpa.13148
Cells. 2022 Dec 29. pii: 142. [Epub ahead of print]12(1):

The Male Mouse Meiotic Cilium Emanates from the Mother Centriole at Zygotene Prior to Centrosome Duplication.

Pablo López-Jiménez, Sara Pérez-Martín, Inés Hidalgo, Francesc R García-Gonzalo, Jesús Page, Rocio Gómez.

  Cilia are hair-like projections of the plasma membrane with an inner microtubule skeleton known as axoneme. Motile cilia and flagella beat to displace extracellular fluids, playing important roles in the airways and reproductive system. On the contrary, primary cilia function as cell-type-dependent sensory organelles, detecting chemical, mechanical, or optical signals from the extracellular environment. Cilia dysfunction is associated with genetic diseases called ciliopathies and with some types of cancer. Cilia have been recently identified in zebrafish gametogenesis as an important regulator of bouquet conformation and recombination. However, there is little information about the structure and functions of cilia in mammalian meiosis. Here we describe the presence of cilia in male mouse meiotic cells. These solitary cilia formed transiently in 20% of zygotene spermatocytes and reached considerable lengths (up to 15-23 µm). CEP164 and CETN3 localization studies indicated that these cilia emanate from the mother centriole prior to centrosome duplication. In addition, the study of telomeric TFR2 suggested that cilia are not directly related to the bouquet conformation during early male mouse meiosis. Instead, based on TEX14 labeling of intercellular bridges in spermatocyte cysts, we suggest that mouse meiotic cilia may have sensory roles affecting cyst function during prophase I.

Keywords:  centrosome; cilia; meiosis; mouse

DOI:  https://doi.org/10.3390/cells12010142
Kidney Res Clin Pract. 2023 Jan 13.

Evaluating the Safety and effectivenesS in adult KorEaN patients treated with Tolvaptan for management of autosomal domInAnt poLycystic kidney disease (ESSENTIAL): short-term outcomes during the titration period.

Hyuk Huh, Yong Soo Kim, Wookyung Chung, Yong Lim Kim, Yaerim Kim, Seungyeup Han, Yeon Soon Jung, Ki Young Na, Kyu Beck Lee, Yun Kyu Oh, Hyeong Cheon Park, Seung Hyeok Han, Tae Hyun Yoo, Yeong Hoon Kim, Soo Wan Kim, Kang Wook Lee, Hayne Cho Park, Sung Gyun Kim, Hyunsuk Kim, Chang Hwa Lee, Kyongtae T Bae, Kook Hwan Oh, Curie Ahn, Hyun Jin Ryu, Yong Chul Kim.

  Background: Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period.Methods: This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19-50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects.
Results: After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (β, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (β, -0.642; p = 0.009).
Conclusion: We observed short-term effects and safety during the tolvaptan titration period, with the greatest decrease in kidney function occurring during the first week. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.

Keywords:  Autosomal dominant polycystic kidney disease; Efficacy; Titration; Tolvaptan

DOI:  https://doi.org/10.23876/j.krcp.22.024
Int J Mol Sci. 2022 Dec 30. pii: 667. [Epub ahead of print]24(1):

Polycystin-1 Is a Crucial Regulator of BIN1 Expression and T-Tubule Remodeling Associated with the Development of Dilated Cardiomyopathy.

Magda C Díaz-Vesga, Raúl Flores-Vergara, Jaime A Riquelme, Marcelo Llancaqueo, Gina Sánchez, Cecilia Vergara, Luis Michea, Paulina Donoso, Andrew F G Quest, Ivonne Olmedo, Zully Pedrozo.

  Cardiomyopathy is commonly observed in patients with autosomal dominant polycystic kidney disease (ADPKD), even when they have normal renal function and arterial pressure. The role of cardiomyocyte polycystin-1 (PC1) in cardiovascular pathophysiology remains unknown. PC1 is a potential regulator of BIN1 that maintains T-tubule structure, and alterations in BIN1 expression induce cardiac pathologies. We used a cardiomyocyte-specific PC1-silenced (PC1-KO) mouse model to explore the relevance of cardiomyocyte PC1 in the development of heart failure (HF), considering reduced BIN1 expression induced T-tubule remodeling as a potential mechanism. PC1-KO mice exhibited an impairment of cardiac function, as measured by echocardiography, but no signs of HF until 7-9 months of age. Of the PC1-KO mice, 43% died suddenly at 7 months of age, and 100% died after 9 months with dilated cardiomyopathy. Total BIN1 mRNA, protein levels, and its localization in plasma membrane-enriched fractions decreased in PC1-KO mice. Moreover, the BIN1 + 13 isoform decreased while the BIN1 + 13 + 17 isoform was overexpressed in mice without signs of HF. However, BIN1 + 13 + 17 overexpression was not observed in mice with HF. T-tubule remodeling and BIN1 score measured in plasma samples were associated with decreased PC1-BIN1 expression and HF development. Our results show that decreased PC1 expression in cardiomyocytes induces dilated cardiomyopathy associated with diminished BIN1 expression and T-tubule remodeling. In conclusion, positive modulation of BIN1 expression by PC1 suggests a novel pathway that may be relevant to understanding the pathophysiological mechanisms leading to cardiomyopathy in ADPKD patients.

Keywords:  BIN1; T-tubule; dilated cardiomyopathy; heart failure; polycystin-1

DOI:  https://doi.org/10.3390/ijms24010667
Nephron. 2023 Jan 06. 1-9

Suspected Autosomal Recessive Polycystic Kidney Disease but Cerebellar Vermis Hypoplasia, Oligophrenia Ataxia, Coloboma, and Hepatic Fibrosis (COACH) Syndrome in Retrospect, A Delayed Diagnosis Aided by Genotyping and Reverse Phenotyping: A Case Report and A Review of the Literature.

Meenakshi Sambharia, Margaret E Freese, Francisco Donato, Girish Bathla, Ibrahim M M Abukhiran, Maisie I Dantuma, M Adela Mansilla, Christie P Thomas.

  The clinical features of cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis (COACH) characterize the rare autosomal recessive multisystem disorder called COACH syndrome. COACH syndrome belongs to the spectrum of Joubert syndrome and related disorders (JSRDs) and liver involvement distinguishes COACH syndrome from the rest of the JSRD spectrum. Developmental delay and oculomotor apraxia occur early but with time, these can improve and may not be readily apparent or no longer need active medical management. Congenital hepatic fibrosis and renal disease, on the other hand, may develop late, and the temporal incongruity in organ system involvement may delay the recognition of COACH syndrome. We present a case of a young adult presenting late to a Renal Genetics Clinic for evaluation of renal cystic disease with congenital hepatic fibrosis, clinically suspected to have autosomal recessive polycystic kidney disease. Following genetic testing, a reevaluation of his medical records from infancy, together with reverse phenotyping and genetic phasing, led to a diagnosis of COACH syndrome.

Keywords:  Cerebellar vermis hypoplasia; Cerebellar vermis hypoplasia, oligophrenia ataxia, coloboma, and hepatic fibrosis syndrome; Congenital hepatic fibrosis; Oculomotor apraxia; Renal cysts; TMEM67

DOI:  https://doi.org/10.1159/000527991
Mol Biol Cell. 2023 Jan 11. mbcE22110508

Basal body organization and cell geometry during the cell cycle in Tetrahymena thermophila.

Huangqingbo Sun, Adam W J Soh, Lisa E Mitchell, Chad G Pearson, Robert F Murphy.

Tetrahymena thermophila possesses arrays of motile cilia that promote fluid flow for cell motility. These consist of intricately organized basal bodies (BBs) that nucleate and position cilia at the cell cortex. Tetrahymena cell geometry and spatial organization of BBs play important roles in cell size, swimming, feeding, and division. How cell geometry and BB organization are established and maintained remains poorly understood, and prior studies have been limited due to difficulties in accurate BB identification and small sample size. We therefore developed an automated image processing pipeline that segments single cells, distinguishes unique BB populations, assigns BBs into distinct ciliary rows, and distinguishes new from mature BBs. We identified unique features to describe the variation of cell shape and BB spatial organization in unsynchronized single-cell images. The results reveal asymmetries in BB distribution and positioning of the cytokinetic furrow within the cell. Moreover, we establish novel spatial and temporal waves in new BB assembly through the cell cycle. Lastly, we used measurements from single cells across the cell cycle to construct a generative model that allows synthesis of movies depicting single cells progressing through the cell cycle. Our approach is expected to be of particular value for characterizing Tetrahymena mutants. [Media: see text].

DOI: https://doi.org/10.1091/mbc.E22-11-0508
J Cell Sci. 2023 Jan 12. pii: jcs.260462. [Epub ahead of print]

Multiple interactions of the dynein-2 complex with the IFT-B complex are required for effective IFT.

Shunya Hiyamizu, Hantian Qiu, Laura Vuolo, Nicola L Stevenson, Caroline Shak, Kate J Heesom, Yuki Hamada, Yuta Tsurumi, Shuhei Chiba, Yohei Katoh, David J Stephens, Kazuhisa Nakayama.

  The dynein-2 complex must be transported anterogradely within cilia to then drive retrograde trafficking of the intraflagellar transport (IFT) machinery containing IFT-A and IFT-B complexes. Here, we screened for potential interactions between the dynein-2 and IFT-B complexes and found multiple interactions among the dynein-2 and IFT-B subunits. In particular, WDR60/DYNC2I1 and the DYNC2H1-DYNC2LI1 dimer from dynein-2, and IFT54 and IFT57 from IFT-B contribute to the dynein-2-IFT-B interactions. WDR60 interacts with IFT54 via a conserved region N-terminal to its light chain-binding regions. Expression of the WDR60 constructs in WDR60-knockout (KO) cells revealed that N-terminal truncation mutants lacking the IFT54-binding site fail to rescue abnormal phenotypes of WDR60-KO cells, such as aberrant accumulation of the IFT machinery around the ciliary tip and on the distal side of the transition zone. However, a WDR60 construct specifically lacking just the IFT54-binding site substantially restored the ciliary defects. In line with the current docking model of dynein-2 with the anterograde IFT trains, these results indicate that extensive interactions involving multiple subunits from the dynein-2 and IFT-B complexes participate in their connection.

Keywords:  Cilia; Dynein-2; IFT-B complex; Intraflagellar transport

DOI:  https://doi.org/10.1242/jcs.260462
Eur Radiol. 2023 Jan 14.

Validation of a semi-automatic method to measure total liver volumes in polycystic liver disease on computed tomography - high speed and accuracy.

Sophie E Aapkes, Thijs R M Barten, Walter Coudyzer, Joost P H Drenth, Ivo M A Geijselaers, Sterre A M Ter Grote, Ron T Gansevoort, Frederik Nevens, Maatje D A van Gastel.

  OBJECTIVES: Polycystic liver disease (PLD) is characterized by growth of hepatic cysts, causing hepatomegaly. Disease severity is determined using total liver volume (TLV), which can be measured from computed tomography (CT). The gold standard is manual segmentation which is time-consuming and requires expert knowledge of the anatomy. This study aims to validate the commercially available semi-automatic MMWP (Multimodality Workplace) Volume tool for CT scans of PLD patients.METHODS: We included adult patients with one (n = 60) or two (n = 46) abdominal CT scans. Semi-automatic contouring was compared with manual segmentation, using comparison of observed volumes (cross-sectional) and growth (longitudinal), correlation coefficients (CC), and Bland-Altman analyses with bias and precision, defined as the mean difference and SD from this difference. Inter- and intra-reader variability were assessed using coefficients of variation (CV) and we assessed the time to perform both procedures.
RESULTS: Median TLV was 5292.2 mL (IQR 3141.4-7862.2 mL) at baseline. Cross-sectional analysis showed high correlation and low bias and precision between both methods (CC 0.998, bias 1.62%, precision 2.75%). Absolute volumes were slightly higher for semi-automatic segmentation (manual 5292.2 (3141.4-7862.2) versus semi-automatic 5432.8 (3071.9-7960.2) mL, difference 2.7%, p < 0.001). Longitudinal analysis demonstrated that semi-automatic segmentation accurately measures liver growth (CC 0.908, bias 0.23%, precision 4.04%). Inter- and intra-reader variability were small (2.19% and 0.66%) and comparable to manual segmentation (1.21% and 0.63%) (p = 0.26 and p = 0.37). Semi-automatic segmentation was faster than manual tracing (19 min versus 50 min, p = 0.009).
CONCLUSIONS: Semi-automatic liver segmentation is a fast and accurate method to determine TLV and liver growth in PLD patients.
KEY POINTS: • Semi-automatic liver segmentation using the commercially available MMWP volume tool accurately determines total liver volume as well as liver growth over time in polycystic liver disease patients. • This method is considerably faster than manual segmentation through the use of Hounsfield unit settings. • We used a real-life CT set for the validation and showed that the semi-automatic tool measures accurately regardless of contrast used for the CT scan or not, presence of polycystic kidneys, liver volume, and previous invasive treatment for polycystic liver disease.

Keywords:  Organ size; Polycystic kidney disease; Polycystic liver disease; Radiology; Tomography, X-ray computed

DOI:  https://doi.org/10.1007/s00330-022-09346-6
J Clin Med. 2022 Dec 31. pii: 317. [Epub ahead of print]12(1):

Novel SPEF2 Variant in a Japanese Patient with Primary Ciliary Dyskinesia: A Case Report and Literature Review.

Mayako Mori, Takashi Kido, Noriho Sakamoto, Mutsumi Ozasa, Kumiko Kido, Yasuko Noguchi, Takatomo Tokito, Daisuke Okuno, Hirokazu Yura, Atsuko Hara, Hiroshi Ishimoto, Takashi Suematsu, Yasushi Obase, Yoshimasa Tanaka, Koichi Izumikawa, Kazuhiko Takeuchi, Hiroshi Mukae.

  Primary ciliary dyskinesia (PCD) is a genetic and congenital disease associated with an abnormal ciliary ultrastructure and function and is estimated to affect 1 in 15,000-20,000 individuals. A PCD diagnosis can be achieved by genotyping. Here, we performed whole-exome analysis for the diagnosis of PCD and described the detailed clinical characteristics of the case. A 39-year-old Japanese woman with sinusitis and bronchiectasis without situs inversus had had upper and lower respiratory symptoms since childhood and had received long-term macrolide therapy without an accurate diagnosis. A moderate deterioration of cilia function was observed by high-speed video microscopy analysis; additionally, the number of cells with moving cilia was fewer than that in patients without PCD. Electron microscopy revealed no apparent structural abnormalities. We performed whole-exome analysis and identified novel biallelic variants of SPEF2 in the homozygous state (c.1860_1861insCT). We confirmed the absence of SPEF2 protein expression in the cilia of the nasal mucosa using fluorescent immunostaining. Accordingly, she was diagnosed as having PCD with the SPEF2 variant. The present case suggests that the deterioration of cilia function is moderate, the number of respiratory cells with moving cilia might be reduced, and the respiratory condition could be severe in patients with PCD with the SPEF2 variant.

Keywords:  SPEF2; ciliary beat amplitude; ciliary beat frequency; high-speed video microscopy analysis; primary ciliary dyskinesia

DOI:  https://doi.org/10.3390/jcm12010317