ctDNA improves prognostic prediction in relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone.

It remains elusive how driver mutations, including those detected in circulating tumor DNA (ctDNA), affect prognosis in relapsed/refractory multiple myeloma (RRMM). Here we performed targeted-capture sequencing using bone marrow plasma cells (BMPC) and ctDNA of 261 RRMM cases uniformly treated with ixazomib, lenalidomide, and dexamethasone in a multicenter, prospective, observational study. We detected 24 and 47 recurrently mutated genes in BMPC and ctDNA, respectively. In addition to clonal hematopoiesis-associated mutations, varying proportion of driver mutations, particularly TP53 mutations (59.2% of mutated cases), were present in only ctDNA, suggesting their subclonal origin. In univariable analyses, ctDNA mutations of KRAS, TP53, DIS3, BRAF, NRAS, and ATM were associated with worse progression-free survival (PFS). BMPC mutations of TP53 and KRAS were associated with inferior PFS, while KRAS mutations were prognostically relevant only when detected in both BMPC and ctDNA. A total number of ctDNA mutations in the six relevant genes was a strong prognostic predictor (2-year PFS rates: 57.3%, 22.7%, and 0% for 0, 1, and ≥ 2 mutations, respectively) and independent of clinical factors and plasma DNA concentration. Using the number of ctDNA mutations, plasma DNA concentration, and clinical factors, we developed a prognostic index (ctRRMM-PI), classifying patients into three categories with 2-year PFS rates of 57.9%, 28.6%, and 0%. Serial analysis of ctDNA mutations in 94 cases revealed that TP53 and KRAS mutations frequently emerge after therapy. Thus, we clarify the genetic characteristics and clonal architecture of ctDNA mutations and demonstrate their superiority over BMPC mutations for prognostic prediction in RRMM.

A prospective, multicenter, observational study of ixazomib plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in Japan.

Real-world studies permit inclusion of a more diverse patient population and provide more information on the effectiveness of treatments used in routine clinical practice. This prospective, multicenter, observational study investigated the effectiveness and safety of ixazomib plus lenalidomide and dexamethasone (IRd) in 295 patients with relapsed/refractory multiple myeloma (RRMM) in routine clinical practice in Japan. Patients had a median age of 74 years, 80.0% were aged ≥ 65 years, 42.0% had received ≥ 3 lines of prior treatment, and 28.5% were "frail" according to the International Myeloma Working Group frailty score. After a median follow-up of 25.0 months, median progression-free survival (PFS) was 15.3 (95% CI 12.4-19.5) months, while median overall survival was not reached. The overall response rate was 53.9%, and 31.5% of patients had a very good partial response or better. In the subgroup analysis, median PFS was better in patients with 1 versus 2 or ≥ 3 lines of prior treatment (29.0 vs 19.2 or 6.9 months) and paraprotein versus clinical relapse (16.0 vs 7.9 months), but median PFS was not notably affected by frailty score or age group. Dose adjustment was more frequent among patients aged > 75 years, especially early after IRd treatment initiation. Treatment-emergent adverse events (TEAEs) of any grade occurred in 84.4% of patients and 24.7% of patients discontinued treatment due to TEAEs; no new safety concerns were found. These findings suggest that oral IRd triplet regimen is an effective and tolerable treatment option for RRMM patients in real-world settings outside of clinical trials.ClinicalTrials.gov identifier: NCT03433001; Date of registration: 14 February 2018.

Identification of "missing links" in C- and D-ring cleavage of steroids by Comamonas testosteroni TA441.

Comamonas testosteroni TA441 is capable of aerobically degrading steroids through the aromatization and cleavage of the A- and B-rings, followed by D- and C-ring cleavage via ß-oxidation. While most of the degradation steps have been previously characterized, a few intermediate compounds remained unidentified. In this study, we proposed that the cleavage of the D-ring at C13-17 required the ScdY hydratase, followed by C-ring cleavage via the ScdL1L2 transferase. The anticipated reaction was expected to yield 6-methyl-3,7-dioxo-decane-1,10-dioic acid-coenzyme A (CoA) ester. To confirm this hypothesis, we constructed a plasmid enabling the induction of targeted genes in TA441 mutant strains. Induction experiments of ScdL1L2 revealed that the major product was 3-hydroxy-6-methyl-7-oxo-decane-1,10-dioic acid-CoA ester. Similarly, induction experiments of ScdY demonstrated that the substrate of ScdY was a geminal diol, 17-dihydroxy-9-oxo-1,2,3,4,5,6,10,19-octanorandrost-8(14)-en-7-oic acid-CoA ester. These findings suggest that ScdY catalyzes the addition of a water molecule at C14 of 17-dihydroxy-9-oxo-1,2,3,4,5,6,10,19-octanorandrost-8(14)-en-7-oic acid-CoA ester, leading to D-ring cleavage at C13-17. Subsequently, the C9 ketone of the D-ring cleavage product is converted to a hydroxyl group, followed by C-ring cleavage, resulting in the production of 3-hydroxy-6-methyl-7-oxo-decane-1,10-dioic acid-CoA ester.IMPORTANCEStudies on bacterial steroid degradation were initiated more than 50 years ago primarily to obtain substrates for steroid drugs. In recent years, the role of steroid-degrading bacteria in relation to human health has gained significant attention, as emerging evidence suggests that the intestinal microflora plays a crucial role in human health. Furthermore, cholic acid, a major component of bile acid secreted in the intestines, is closely associated with the gut microbiota. While Comamonas testosteroni TA441 is recognized as the leading bacterial model for aerobic steroid degradation, the involvement of aerobic steroid degradation in the intestinal microflora remains largely unexplored. Nonetheless, the presence of C. testosteroni in the cecum suggests the potential influence of aerobic steroid degradation on gut microbiota. To establish essential information about the role of these bacteria, here, we identified the missing compounds and propose more details of C-, and D-ring cleavage, which have remained unclear until now.

Comprehensive summary of steroid metabolism in Comamonas testosteroni TA441: entire degradation process of basic four rings and removal of C12 hydroxyl group.

Comamonas testosteroni is one of the representative aerobic steroid-degrading bacteria. We previously revealed the mechanism of steroidal A,B,C,D-ring degradation by C. testosteroni TA441. The corresponding genes are located in two clusters at both ends of a mega-cluster of steroid degradation genes. ORF7 and ORF6 are the only two genes in these clusters, whose function has not been determined. Here, we characterized ORF7 as encoding the dehydrase responsible for converting the C12ß hydroxyl group to the C10(12) double bond on the C-ring (SteC), and ORF6 as encoding the hydrogenase responsible for converting the C10(12) double bond to a single bond (SteD). SteA and SteB, encoded just upstream of SteC and SteD, are in charge of oxidizing the C12α hydroxyl group to a ketone group and of reducing the latter to the C12ß hydroxyl group, respectively. Therefore, the C12α hydroxyl group in steroids is removed with SteABCD via the C12 ketone and C12ß hydroxyl groups. Given the functional characterization of ORF6 and ORF7, we disclose the entire pathway of steroidal A,B,C,D-ring breakdown by C. testosteroni TA441.IMPORTANCEStudies on bacterial steroid degradation were initiated more than 50 years ago, primarily to obtain materials for steroid drugs. Now, their implications for the environment and humans, especially in relation to the infection and the brain-gut-microbiota axis, are attracting increasing attention. Comamonas testosteroni TA441 is the leading model of bacterial aerobic steroid degradation with the ability to break down cholic acid, the main component of bile acids. Bile acids are known for their variety of physiological activities according to their substituent group(s). In this study, we identified and functionally characterized the genes for the removal of C12 hydroxyl groups and provided a comprehensive summary of the entire A,B,C,D-ring degradation pathway by C. testosteroni TA441 as the representable bacterial aerobic degradation process of the steroid core structure.

Role of Magnetic Resonance Imaging in the Screening of Closed Spinal Dysraphism.

Closed spinal dysraphism (CSD) encompasses a heterogeneous group of spinal cord deformities, which can be accompanied by several types of skin stigmata. These skin stigmata may include inconspicuous features, such as sacral dimples and deformed gluteal clefts, but the association between such mild skin stigmata and CSD is uncertain. This study aimed to reevaluate the indication for magnetic resonance imaging (MRI) in patients with skin stigmata while considering the indication for surgery. A retrospective analysis was conducted on magnetic resonance images of 1255 asymptomatic children with skin stigmata between 2003 and 2015. Skin stigmata classification was based on medical chart data. All subtypes of CSDs except for filum terminale lipomas (FTL), FTL thicker than 2 mm or with low conus medullaris, were considered to meet the surgical indication. CSD prevalence was estimated while considering the surgical indications and assessed after excluding all FTL cases. Skin stigmata were classified into seven types, dimple, deformed gluteal cleft, hair, subcutaneous mass, appendage, discoloration, and protruding bone, and included 1056 isolated and 199 complex ones. The prevalence of CSD was 19.5%, 6.8%, and 0.5% among patients with isolated dimples (n = 881) and 13.9%, 5.8%, and 0.7% among those with isolated deformed gluteal clefts (n = 136) for all cases, surgical indications, and patients without FTL, respectively. Dimples and deformed gluteal clefts had a low prevalence of CSD requiring surgical intervention, and cases without FTL were rare. Asymptomatic patients with mild skin stigmata may not require immediate MRI.

Technical evolution of pediatric neurosurgery: moyamoya disease.

Moyamoya disease (MMD) is a rare steno-occlusive disease of the bilateral internal carotid arteries that predominantly occurs in East Asia. Since the first description of the MMD by Suzuki and Takaku in 1969, significant advances have been made in both basic and clinical understanding of the disease. The incidence and prevalence of pediatric MMD have increased, potentially due to improved detection rates. The advancement of neuroimaging techniques has enabled MRI-based diagnostics and detailed visualization of the vessel wall. Various methods of surgical treatments are successful in pediatric MMD patients, and recent studies emphasize the importance of reducing postoperative complications since the goal of MMD surgery is to prevent future cerebral infarction and hemorrhage. Long-term outcomes following appropriate surgical treatment in pediatric MMD patients have shown promising results, including favorable outcomes in very young patients. Further studies with a large patient cohort are needed to establish individualized risk group stratification for determining the optimal timing of surgical treatment and to conduct multidisciplinary outcome assessments.

Harnessing microbial phylum-specific molecular markers for assessment of environmental estrogen degradation.

Steroidal estrogens are ubiquitous contaminants that have garnered attention worldwide due to their endocrine-disrupting and carcinogenic activities at sub-nanomolar concentrations. Microbial degradation is one of the main mechanisms through which estrogens can be removed from the environment. Numerous bacteria have been isolated and identified as estrogen degraders; however, little is known about their contribution to environmental estrogen removal. Here, our global metagenomic analysis indicated that estrogen degradation genes are widely distributed among bacteria, especially among aquatic actinobacterial and proteobacterial species. Thus, by using the Rhodococcus sp. strain B50 as the model organism, we identified three actinobacteria-specific estrogen degradation genes, namely aedGHJ, by performing gene disruption experiments and metabolite profile analysis. Among these genes, the product of aedJ was discovered to mediate the conjugation of coenzyme A with a unique actinobacterial C17 estrogenic metabolite, 5-oxo-4-norestrogenic acid. However, proteobacteria were found to exclusively adopt an α-oxoacid ferredoxin oxidoreductase (i.e., the product of edcC) to degrade a proteobacterial C18 estrogenic metabolite, namely 3-oxo-4,5-seco-estrogenic acid. We employed actinobacterial aedJ and proteobacterial edcC as specific biomarkers for quantitative polymerase chain reaction (qPCR) to elucidate the potential of microbes for estrogen biodegradation in contaminated ecosystems. The results indicated that aedJ was more abundant than edcC in most environmental samples. Our results greatly expand the understanding of environmental estrogen degradation. Moreover, our study suggests that qPCR-based functional assays are a simple, cost-effective, and rapid approach for holistically evaluating estrogen biodegradation in the environment.

Successful renal recovery from multiple myeloma-associated crystalline light chain cast nephropathy and accompanying acute kidney injury with early use of bortezomib-based therapy: a case report and literature review.

Crystalline light chain cast nephropathy is a rare distinct morphologic variant of light chain cast nephropathy which is the most common renal lesion associated with multiple myeloma. It is often related to high myeloma tumor burden, severe acute kidney injury, and an unfavorable prognosis. A 79-year-old Japanese man was referred to our medical center with anemia, proteinuria, and acute exacerbation of the serum creatinine accompanying anuria. A renal biopsy showed crystalline cast filling the tubular lumens, injured tubular cells, and inflammatory cells infiltration of interstitium. Serum and urine immunofixation detected a monoclonal protein (IgA-λ and Bence-Jones Protein-λ, respectively), and bone marrow examination observed 64% of plasma cells. IgA-λ type multiple myeloma-associated crystalline light chain cast nephropathy and accompanying acute kidney injury were confirmed. Hydration and emergency hemodialysis were immediately introduced, and the treatment with bortezomib and dexamethasone was initiated. The patient showed successful recovery in renal manifestations. We suggest that early use with bortezomib-based therapy should be considered for patients with acute kidney injury caused by multiple myeloma-associated crystalline light chain cast nephropathy.

[Surgery for Spinal Lipoma of the Conus Medullaris].

Lipoma of the conus medullaris(LCM)can cause neurological symptoms known as tethered cord syndrome(TCS). The symptoms can be seen at diagnosis and during long-term follow-up. Even after surgical treatment, some patients can present with neurological deterioration indicating a TCS, defined as retethered cord syndrome(ReTCS). In this report the surgical technique for conus lipoma comprising wide osteoplastic laminotomy with confirmed whole spinal lipoma and adjacent normal spinal tissue is described, with dissection performed from the proximal side to the distal side with confirmed normal spinal cord and roots under operative microscope, expansive dural plasty aiming to get low cord/sac ratio was reported. Considering that some patients with LCM show postoperative neurological symptoms due to TCS in a long-term follow-up period, careful postoperative follow-up is necessary.

[Moyamoya Disease in Infants and Toddlers].

Treatment for moyamoya disease in infants and toddlers is challenging, because of the progressiveness of the disease. Revascularization surgery is the first-line therapy and should be performed as early as possible after diagnosis to prevent additional cerebral infarction. This review describes in detail the changes in the new "Diagnostic Criteria 2021 for moyamoya disease", and discusses the concept of treatment including indirect and combined bypass surgery in infants and toddlers. Surgical technique and perioperative management based on our experience are also precisely described.

Transcortical Endoscopic Removal of Residual Craniopharyngioma in the Third Ventricle: Surgical Video.

Excision through craniotomy is used for pediatric craniopharyngioma removal. However, residual tumors can sometimes be found in the blind spot of the microscopic field, such as the third ventricle wall, back of the optic chiasm, and brainstem surface, during surgery. Video 1 demonstrates the surgery using a flexible endoscope for the removal of residual tumor located within the blind spot of the first resection. The written consent was obtained from the patient's family. A 4-year-old child complained of vomiting, and the radiologic findings showed obstructive hydrocephalus and a calcified suprasellar mass lesion that extended to the third ventricle. The tumor was treated with a right frontotemporal craniotomy. The pathologic diagnosis was craniopharyngioma. Postoperative magnetic resonance imaging showed residual tumor detected at the roof of the third ventricle, back of the optic chiasm, and interpeduncular fossa. The residual tumors were removed using a flexible endoscope via a transcortical, transventricular approach. Postoperative magnetic resonance imaging showed no residual tumors. Although histologically benign, craniopharyngiomas may be locally aggressive and their close proximity to vital structures makes them one of our controversial management dilemmas. Recurrence may occur following even a presumed total excision and radiation therapy. Residual tumors located in the third ventricle are resected through various approaches, such as the transsphenoidal or transcallosal approach. Our approach using a flexible endoscope was minimally invasive and useful for the removal of residual tumor of the third ventricle in craniopharyngioma surgery because the approach offered a wide field of view and visual angle and forceps could be applied according to the view.

Ocular Ischemic Syndrome due to Internal Carotid Artery Occlusion with Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF-1) is associated with multiple vascular abnormalities, including internal carotid artery (ICA) stenosis/occlusion. Depending on the site of stenosis/occlusion of the ICA, both cerebral circulation and ocular circulation can be impaired. We describe a rare pediatric case of ocular ischemic syndrome (OIS) due to ICA occlusion in NF-1. The patient diagnosed with NF-1 suffered right ICA occlusion at 12 years of age, and developed right dense vitreous hemorrhage due to OIS at 13 years of age. The patient underwent right cerebral revascularization surgery to improve cerebral and ocular ischemia, but the visual acuity of the right eye did not improve. This case suggests that attention should be paid not only to cerebral ischemia but also to ocular ischemia in patients with ICA stenosis/occlusion of NF-1. Surgical interventions such as cerebral revascularization surgery should be considered in the early stages of OIS to protect visual function, and careful follow-up is required.

Identification of essential ß-oxidation genes and corresponding metabolites for oestrogen degradation by actinobacteria.

Steroidal oestrogens (C18 ) are contaminants receiving increasing attention due to their endocrine-disrupting activities at sub-nanomolar concentrations. Although oestrogens can be eliminated through photodegradation, microbial function is critical for removing oestrogens from ecosystems devoid of sunlight exposure including activated sludge, soils and aquatic sediments. Actinobacteria were found to be key oestrogen degraders in manure-contaminated soils and estuarine sediments. Previously, we used the actinobacterium Rhodococcus sp. strain B50 as a model microorganism to identify two oxygenase genes, aedA and aedB, involved in the activation and subsequent cleavage of the estrogenic A-ring respectively. However, genes responsible for the downstream degradation of oestrogen A/B-rings remained completely unknown. In this study, we employed tiered comparative transcriptomics, gene disruption experiments and mass spectrometry-based metabolite profile analysis to identify oestrogen catabolic genes. We observed the up-regulation of thiolase-encoding aedF and aedK in the transcriptome of strain B50 grown with oestrone. Consistently, two downstream oestrogenic metabolites, 5-oxo-4-norestrogenic acid (C17 ) and 2,3,4-trinorestrogenic acid (C15 ), were accumulated in aedF- and aedK-disrupted strain B50 cultures. Disruption of fadD3 [3aα-H-4α(3'-propanoate)-7aß-methylhexahydro-1,5-indanedione (HIP)-coenzyme A-ligase gene] in strain B50 resulted in apparent HIP accumulation in oestrone-fed cultures, indicating the essential role of fadD3 in actinobacterial oestrogen degradation. In addition, we detected a unique meta-cleavage product, 4,5-seco-estrogenic acid (C18 ), during actinobacterial oestrogen degradation. Differentiating the oestrogenic metabolite profile and degradation genes of actinobacteria and proteobacteria enables the cost-effective and time-saving identification of potential oestrogen degraders in various ecosystems through liquid chromatography-mass spectrometry analysis and polymerase chain reaction-based functional assays.

Retethering risk in pediatric spinal lipoma of the conus medullaris.

OBJECTIVE: Lipoma of the conus medullaris (LCM) causes neurological symptoms known as tethered cord syndrome (TCS). The symptoms can be seen at diagnosis and during long-term follow-up. In this report, pediatric patients with LCMs who underwent untethering surgery, under the policy of performing surgery if diagnosed regardless of symptoms, were retrospectively reviewed to evaluate long-term surgical outcomes. Possible risk factors for retethered cord syndrome (ReTCS) were evaluated in the long-term follow-up period. METHODS: A total of 51 consecutive pediatric patients with LCMs who underwent a first untethering surgery and were followed for > 100 months were retrospectively analyzed. The surgery was performed with the partial removal technique. Pre- and postoperative clinical and radiological data were reviewed to analyze the outcomes of surgery and identify potential risk factors for ReTCS. RESULTS: During follow-up, 12 patients experienced neurological deterioration due to ReTCS. The overall 10-year and 15-year progression-free survival rates were 82.3% and 75.1%, respectively. On univariate analysis, a lipoma type of lipomyelomeningocele (OR 11, 95% CI 2.50-48.4; p = 0.0014), patient age at the time of surgery (OR 0.41, 95% CI 0.14-1.18; p = 0.0070), and the mean patient growth rate after surgery (OR 2.00, 95% CI 1.12-3.41; p = 0.0040) were significant factors associated with ReTCS. Cox proportional hazard models showed that a lipoma type of lipomyelomeningocele (HR 5.16, 95% CI 1.54-20.1; p = 0.010) and the mean growth rate after surgery (HR 1.88, 95% CI 1.00-3.50; p = 0.040) were significantly associated with the occurrence of ReTCS. CONCLUSIONS: More complex lesions and a high patient growth rate after surgery seemed to indicate increased risk of ReTCS. Larger prospective studies and registries are needed to define the risks of ReTCS more adequately.

Identification of the Coenzyme A (CoA) Ester Intermediates and Genes Involved in the Cleavage and Degradation of the Steroidal C-Ring by Comamonas testosteroni TA441.

Comamonas testosteroni TA441 degrades steroids aerobically via aromatization of the A-ring accompanied by B-ring cleavage, followed by D- and C-ring cleavage. We previously revealed major enzymes and intermediate compounds in A,B-ring cleavage, the ß-oxidation cycle of the cleaved B-ring, and partial C,D-ring cleavage. Here, we elucidate the C-ring cleavage and the ß-oxidation cycle that follows. ScdL1L2, a 3-ketoacid coenzyme A (CoA) transferase which belongs to the SugarP_isomerase superfamily, was thought to cleave the C-ring of 9-oxo-1,2,3,4,5,6,10,19-octanor-13,17-secoandrost-8(14)-ene-7,17-dioic acid-CoA ester, the key intermediate compound in the degradation of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid (3aα-H-4α [3'-propionic acid]-7aß-methylhexahydro-1,5-indanedione; HIP)-CoA ester in our previous study; however, the present study suggested that ScdL1L2 is the isomerase of the derivative with a hydroxyl group at C-14 which cleaves the C-ring. The subsequent ring-cleaved product was indicated to be converted to 4-methyl-5-oxo-octane-1,8-dioic acid-CoA ester mainly by ORF33-encoded CoA-transferase (named ScdJ), followed by dehydrogenation by ORF21- and 22-encoded acyl-CoA dehydrogenase (named ScdM1M2). Then, a water molecule is added by ScdN for further degradation by ß-oxidation. ScdN is proposed to catalyze the last reaction in C,D-ring degradation by the enzymes encoded in the steroid degradation gene cluster tesB to tesR. IMPORTANCE Studies on bacterial steroid degradation were initiated more than 50 years ago primarily to obtain materials for steroid drugs. Steroid-degrading bacteria are globally distributed, and the role of bacterial steroid degradation in the environment, as well as in humans, is attracting attention. The overall degradation process of the four steroidal rings has been proposed; however, there is still much to be revealed to understand the complete degradation pathway. This study aimed to uncover the whole steroid degradation process in C. testosteroni, which is one of the most studied representative steroid-degrading bacteria and is suitable for exploring the degradation pathway because the involvement of degradation-related genes can be determined by gene disruption.

Light Chain Deposition Disease Diagnosed Using Computed Tomography-Guided Kidney Biopsy.

Light chain deposition disease (LCDD) is characterized by the deposition of monoclonal immunoglobulin light chains in the kidney, which can cause end-stage kidney disease if not treated. While kidney biopsy is required for definitive diagnosis, choosing an appropriate biopsy method may be problematic when examining patients with atrophic kidneys. A 66-year-old Japanese man was referred to our institution with a three-month history of leg edema. Clinical investigations revealed proteinuria levels of 7.5 g/day. CT-guided percutaneous kidney biopsy was selected as the biopsy method because atrophic kidneys were poorly visualized on ultrasonography. Kidney biopsy revealed nodular glomerulosclerosis, exclusive deposition of the κ chain, and powdery electron-dense deposits, all of which were indicative of LCDD. Bence-Jones protein was detected in the urine. The patient also had an abnormal serum-free light chain ratio. Bone marrow biopsy revealed multiple myeloma; therefore, the patient was diagnosed to have LCDD with multiple myeloma. The patient was treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone. After a one-year follow-up, the patient had hematological and renal responses without any treatment-related adverse effects. Our case demonstrates the effectiveness of daratumumab as a treatment for LCDD with nephrotic-range proteinuria. Additionally, we suggest that CT-guided kidney biopsy should be considered as a diagnostic test in patients with kidney atrophy when making a definitive diagnosis.

Reconversion to ventriculoperitoneal shunt following ventriculoatrial shunt malfunction in children.

PURPOSE: To analyze the long-term efficacy of the ventriculoatrial shunt (VAS) in pediatric patients with hydrocephalus, focusing on the atrial catheter and suitable revision procedures of the distal catheter following VAS malformation performed at our institution. METHODS: The authors retrospectively analyzed data of 28 pediatric patients under the age of 10 years who were treated with VAS for hydrocephalus and who had a follow-up period of at least 5 years. RESULTS: A total of 42 atrial tube revision procedures were performed in 28 patients during the study period. The median atrial tube survival time due to atrial tube obstruction was 2.32 years (n = 31, range: 0.4-8.08 years). Atrial tube survival time was shorter in younger children (p < 0.0001) and in children who were shorter in height (p = 0.0001). As a revision procedure following atrial tube malfunction, 22 (78.6%) out of the 28 patients who had an inserted VAS had the VAS reconversion into a VPS at the last follow-up. CONCLUSIONS: VAS can be a useful alternative to VPS, but it requires frequent atrial tube revisions, especially in younger children. Reconversion to VPS after VAS malfunction is a reasonable option and is associated with longer shunt survival time despite its previously observed difficulties.