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Cureus Aug 2023Introduction The utilization of robot-assisted technique for splenectomy has recently gained popularity especially in patients undergoing splenectomy for hematological...
Introduction The utilization of robot-assisted technique for splenectomy has recently gained popularity especially in patients undergoing splenectomy for hematological indications owing to its magnification of and easy manipulation of internal abdominal organs. Moreover, robotic splenectomy emerged as an essential teaching module before approaching more complex robotic procedures. Methods A total of 43 elective splenectomies were performed for hematological indications in Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) between January 2018 to July 2023 of which 14 patients underwent robotic splenectomy. All patients underwent lateral approach of robotic splenectomy with a modification of avoiding the lesser sac dissection. Prospectively maintained data were retrospectively analyzed and results were recorded in terms of intra-operative time taken, blood loss, need for blood and blood product transfusion and postoperative morbidity and mortality. Results The indications for patients who underwent robotic splenectomy include idiopathic thrombocytopenic purpura in eight patients, autoimmune hemolytic anemia in three patients, Evans syndrome in one patient and hereditary spherocytosis in two patients. The median splenic diameter was 14.8cm and the median platelet count before the operation was 10,800 cells/cubic millimeter (7000-3,20,000). The mean operative time was 92 minutes and blood loss was 40ml. The median duration of hospital stay was 2.4 days. All 14 patients had therapeutic success and there was no procedure-related mortality or morbidity. Conclusion Robotic splenectomy using the modified lateral approach can safely be performed with comparable operative time, blood loss and overall morbidity. However further studies are mandatory to confirm the advantage of this modified technique of lateral approach of robotic splenectomy.
PubMed: 37736466
DOI: 10.7759/cureus.43820 -
Frontiers in Pediatrics 2023Hereditary Spherocytosis (HS) is a rare, congenital red blood cell disorder presenting with variable clinical manifestations ranging from mild hemolytic anemia to severe...
Hematological characteristics and hepatobiliary complications of hereditary spherocytosis in a tertiary care pediatric center: optimizing diagnosis and care through local and international networks.
BACKGROUND
Hereditary Spherocytosis (HS) is a rare, congenital red blood cell disorder presenting with variable clinical manifestations ranging from mild hemolytic anemia to severe anemia with hypersplenism and hepatobiliary complications.
METHODS
The objectives of the study were to evaluate the diagnostic pathway of HS, the presence and management of hepatobiliary complications in pediatric patients with HS followed in a tertiary care center. The demographic, clinical, hematological information were retrieved from medical records of patients having at least 1 hematology visit between 2010 and 2020.
RESULTS
Forty-two patients were enrolled, 23 M. Mean age at onset of symptoms was 2.8 years, at diagnosis was 3.5 years. Anemia was the first manifestation in 73%; suspect of HS arose for all patients in first or second level outpatient clinics. Only 64% of patients performed two confirmation tests in the reference center. 28/42 had familiarity for HS; of the 13/42 who did not, only 47% performed further analysis. Sixteen patients developed gallbladder stones (40%), visible at the first ultrasound (5.6 years). Hemolytic crises and parvovirus infections were more frequent in patients with stones (53.6% vs. 26.1% and 63.6% vs. 28.6%, respectively). 10/16 (62.5%) underwent elective cholecystectomy: 8 had concomitant splenectomy.
CONCLUSIONS
our study highlights the need to optimize the diagnostic pathway in networks of care involving general and specialized centers in order to reduce time to diagnosis and ensure that all patients receive confirmatory tests. A high frequency of hepatobiliary complications since young age was observed suggesting that screening with ultrasound should begin earlier.
PubMed: 37886235
DOI: 10.3389/fped.2023.1269645 -
Frontiers in Immunology 2023Elective splenectomy is the main treatment for a wide range of haematological diseases. Porto-spleno-mesenteric venous thrombosis represents one of the most severe...
BACKGROUND
Elective splenectomy is the main treatment for a wide range of haematological diseases. Porto-spleno-mesenteric venous thrombosis represents one of the most severe complications of this procedure. The aim of this study was to evaluate risk factors associated with development of porto-spleno-mesenteric venous thrombosis after elective splenectomy.
METHODS
All cases of elective splenectomy carried out from April 1 2017 to January 31 2023 were included in this single centre retrospective cohort study. Patients' demographics and perioperative data were analysed and correlated with the incidence of postoperative thrombosis. All patients underwent postoperative doppler ultrasound screening for thrombosis. Analysis was performed using SPSS 28, with p-value < 0.05 considered significant.
RESULTS
Twenty-two patients (10 women, 12 men) underwent splenectomy during the study period. Indications were: immune thrombocytopenia (n: 6), myeloproliferative disorder (n: 6), hereditary spherocytosis (n: 4), thalassemia (n: 1), lymphoma (n: 1), leukaemia (n: 1), other malignancies (n: 3). Six patients developed porto-spleno-mesenteric venous thrombosis and only 2 of them were symptomatic. Patients were treated with anticoagulation therapy with complete resolution. Analysis identified three main factors associated with thrombosis: spleen diameter (p = 0.03), myeloproliferative disorder (p = 0.02), intraoperative platelet transfusion (p = 0.002) and intraoperative red blood cells transfusion (p = 0.009).
CONCLUSION
Standardized postoperative screening allows prompt diagnosis and treatment of porto-spleno-mesenteric venous thrombosis even in asymptomatic cases. Patient with splenomegaly and affected by myeloproliferative disorder have a greater risk to develop this complication.
Topics: Male; Humans; Female; Spleen; Splenectomy; Retrospective Studies; Venous Thrombosis; Thrombosis; Myeloproliferative Disorders
PubMed: 37928557
DOI: 10.3389/fimmu.2023.1216283 -
Molecular Imaging and Radionuclide... Oct 2023A 7-year-old boy with known diagnosis of hereditary spherocytosis and ulcerative colitis was referred for F-fluorodeoxyglucose (F-FDG) positron emission...
A 7-year-old boy with known diagnosis of hereditary spherocytosis and ulcerative colitis was referred for F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography after detection of a 28 mm lesion suspicious for malignancy in spleen on upper abdomen magnetic resonance imaging (MRI). As an incidental finding, a moderately increased uptake of F-FDG was observed in periportal region with no definable mass. MRI revealed compatible findings with "periportal cuffing" as described on ultrasonography.
PubMed: 37870391
DOI: 10.4274/mirt.galenos.2023.53254 -
Biomolecules Dec 2023Piezo1 is a mechanosensitive ion channel required for various biological processes, but its regulation remains poorly understood. Here, we used erythrocytes to address...
Piezo1 is a mechanosensitive ion channel required for various biological processes, but its regulation remains poorly understood. Here, we used erythrocytes to address this question since they display Piezo1 clusters, a strong and dynamic cytoskeleton and three types of submicrometric lipid domains, respectively enriched in cholesterol, GM1 ganglioside/cholesterol and sphingomyelin/cholesterol. We revealed that Piezo1 clusters were present in both the rim and the dimple erythrocyte regions. Upon Piezo1 chemical activation by Yoda1, the Piezo1 cluster proportion mainly increased in the dimple area. This increase was accompanied by Ca influx and a rise in echinocytes, in GM1/cholesterol-enriched domains in the dimple and in cholesterol-enriched domains in the rim. Conversely, the effects of Piezo1 activation were abrogated upon membrane cholesterol depletion. Furthermore, upon Piezo1-independent Ca influx, the above changes were not observed. In healthy donors with a high echinocyte proportion, Ca influx, lipid domains and Piezo1 fluorescence were high even at resting state, whereas the cytoskeleton membrane occupancy was lower. Accordingly, upon decreases in cytoskeleton membrane occupancy and stiffness in erythrocytes from patients with hereditary spherocytosis, Piezo1 fluorescence was increased. Altogether, we showed that Piezo1 was differentially controlled by lipid domains and the cytoskeleton and was favored by the stomatocyte-discocyte-echinocyte transformation.
Topics: Humans; Cholesterol; Cytoskeleton; Erythrocytes; G(M1) Ganglioside; Microtubules; Lipid Bilayers; Ion Channels
PubMed: 38254651
DOI: 10.3390/biom14010051 -
Children (Basel, Switzerland) Nov 2023Same-day discharge after a cholecystectomy is a common practice in the adult population and has been demonstrated as safe and viable for children as well. However, there...
BACKGROUND
Same-day discharge after a cholecystectomy is a common practice in the adult population and has been demonstrated as safe and viable for children as well. However, there is a lack of comprehensive teaching models for pediatric cholecystectomy. Drawing inspiration from standardized outpatient procedures, this study aimed to assess the clinical outcomes and feasibility of teaching programs and an Enhanced Recovery After Surgery (ERAS) protocol following ambulatory laparoscopic cholecystectomy in pediatric patients.
METHODS
In 2015, an ERAS pathway for laparoscopic cholecystectomy (LC) was implemented, focusing on admission procedures, surgery timing, anesthetic choices, analgesia, postoperative feeding, mobilization, and pain assessment. Day-case surgery was not applicable for acute cholecystitis, choledochal lithiasis, sickle cell disease, and hereditary spherocytosis cases. The protocol was employed for a group of attending surgeons and fellows, as well as a group of residents under the supervision of experienced surgeons. A retrospective analysis was conducted to evaluate the feasibility and effectiveness of ambulatory cholecystectomy in children and its utilization in training pediatric surgical trainees.
RESULTS
Between 2015 and 2020, a total of 33 patients were included from a cohort of 162 children who underwent LC, with 15 children operated on by senior surgeons and 18 by young surgeons. The primary diagnoses were symptomatic gallbladder lithiasis ( = 32) and biliary dyskinesia ( = 1). The median age at the time of surgery was 11.3 years (interquartile range (IQR) 4.9-18), and the median duration of surgery was 54 min (IQR 13-145). One intraoperative complication occurred, involving gallbladder rupture and the dissemination of lithiasis into the peritoneal cavity. Three patients (9%) required an overnight stay, while no postoperative complications or readmissions within 30 days were observed. ERAS was successfully implemented in 30 patients (91%). No significant differences in surgical outcomes were noted between senior and young surgeons. At an average follow-up of 55 months, no long-term sequelae were identified.
CONCLUSIONS
These findings align with the current trend of increasing use of outpatient laparoscopic cholecystectomy and underscore its feasibility in the pediatric population. The application of a structured ERAS protocol appears viable and practical for training the next generation of pediatric surgeons.
LEVEL OF EVIDENCE
Level III.
PubMed: 38136083
DOI: 10.3390/children10121881 -
Asian Journal of Surgery May 2024
PubMed: 38816272
DOI: 10.1016/j.asjsur.2024.05.089 -
EMBO Reports Apr 2024Stop codon readthrough (SCR) is the process where translation continues beyond a stop codon on an mRNA. Here, we describe a strategy to enhance or induce SCR in a...
Stop codon readthrough (SCR) is the process where translation continues beyond a stop codon on an mRNA. Here, we describe a strategy to enhance or induce SCR in a transcript-selective manner using a CRISPR-dCas13 system. Using specific guide RNAs, we target dCas13 to the region downstream of canonical stop codons of mammalian AGO1 and VEGFA mRNAs, known to exhibit natural SCR. Readthrough assays reveal enhanced SCR of these mRNAs (both exogenous and endogenous) caused by the dCas13-gRNA complexes. This effect is associated with ribosomal pausing, which has been reported for several SCR events. Our data show that CRISPR-dCas13 can also induce SCR across premature termination codons (PTCs) in the mRNAs of green fluorescent protein and TP53. We demonstrate the utility of this strategy in the induction of readthrough across the thalassemia-causing PTC in HBB mRNA and hereditary spherocytosis-causing PTC in SPTA1 mRNA. Thus, CRISPR-dCas13 can be programmed to enhance or induce SCR in a transcript-selective and stop codon-specific manner.
Topics: Animals; Codon, Terminator; Clustered Regularly Interspaced Short Palindromic Repeats; RNA, Guide, CRISPR-Cas Systems; Codon, Nonsense; RNA, Messenger; Protein Biosynthesis; Mammals
PubMed: 38499809
DOI: 10.1038/s44319-024-00115-8 -
Clinica Chimica Acta; International... Aug 2023Osmotic gradient ektacytometry is an important method for diagnosis of red blood cell membrane disorders. For interpretation of the osmoscan parameters on the...
BACKGROUND AND AIMS
Osmotic gradient ektacytometry is an important method for diagnosis of red blood cell membrane disorders. For interpretation of the osmoscan parameters on the ektacytomety, an age-matched control sample drawn at the same time is recommended for direct comparison. However, this can be challenging for laboratories to fulfil, especially when ektacytometry is performed in children. Therefore, the aim of this study was to evaluate the influence of age and sex on the osmoscan parameters.
MATERIALS AND METHODS
Blood samples from 231 subjects were analyses on a LoRRca MaxSIS. Data were investigated for need of partitioning by age and sex. After outlier detection, reference intervals (RIs) for osmoscan parameters were estimated.
RESULTS
For all parameters except EImin, lower values were observed in infants < 3 month (N = 50) than in all other age group. Hence, RIs were calculated separately for this age group. For EImin, a unified RI was calculated. No difference between sexes was observed for any of the parameters.
CONCLUSION
Lower RIs and a left shift in the osmoscan curves were observed in infants < 3 months compared with older subjects. Hence, age-matched controls are necessary when evaluating ektacytometry in newborns, but can be ignored in older children and adults. This will ease the laboratory workflow when performing ektacytometry.
Topics: Infant, Newborn; Adult; Child; Infant; Humans; Osmosis; Erythrocyte Membrane; Laboratories; Workflow
PubMed: 37659465
DOI: 10.1016/j.cca.2023.117532 -
Frontiers in Genetics 2023Hereditary spherocytosis (HS) is a congenital haemolytic anaemia attributed to dysregulation or abnormal quantities of erythrocyte membrane proteins. Currently, the...
Hereditary spherocytosis (HS) is a congenital haemolytic anaemia attributed to dysregulation or abnormal quantities of erythrocyte membrane proteins. Currently, the most common erythrocytic gene, spectrin β (), variants are located in exons and give rise to mRNA defects. However, the genetic characteristics and pathogenic mechanisms of intronic variants are not completely understood. This study aimed to analyse a rare intronic inversion variant in the gene associated with HS, and explore the impact of the variant on mRNA splicing. The clinical manifestations of the patient were summarised and analysed for spherocytosis phenotype diagnosis. The pathogenic variant was identified in the proband using targeted next-generation and Sanger sequencing. RNA sequencing was performed to analyse whether gene splicing and expression were affected. Targeted next-generation sequencing identified a novel disease-associated intronic inversion variant of the gene in the proband. The inversion variant was located between intron 19 and 20, and contained the entire exon 20 and partial sequences of adjacent introns. Sanger sequencing confirmed that the intronic inversion variant only appeared in the genome of the proband, not in his parents. RNA sequencing revealed that the variant could result in the skipping of exon 20 and reduced expression of mRNA. This study identifies a rare intronic inversion variant in the gene associated with hereditary spherocytosis. The pathogenic variant can lead to exon 20 skipping and decreased gene expression. This finding has not been previously reported in any literature. This study can expand the intronic variant spectrum of the gene, deepen our understanding of HS pathogenesis, and contribute to the genetic diagnosis and clinical management of patients.
PubMed: 38111681
DOI: 10.3389/fgene.2023.1309040