Chimeric Antigen Receptor T Cells With Modified Interleukin-13 Preferentially Recognize IL13Rα2 and Suppress Malignant Glioma: A Preclinical Study.

Background: Interleukin-13 receptor α 2 (IL13Rα2) is a promising tumor-directed antigen of malignant glioma (MG). Here, we examine the efficacy and safety of T cells containing a YYB-103 chimeric antigen receptor (CAR) that can preferentially bind to IL13Rα2 on MG cells. Methods: IL13 was modified on the extracellular domain by substitution of amino acids with E13K, R66D, S69D, and R109K and stably transfected into human T cells using a retroviral vector. The in vitro efficacy of YYB-103 CAR T cells was tested in cell lines with differing IL13Rα1 and IL13Rα2 expression. The in vivo efficacy of intracerebroventricular (i.c.v.) and intravenous (i.v.) routes of YYB-103 CAR T-cell administration were tested in orthotopic MG mouse models. Immunohistochemical staining of MG was performed using WHO grade 3/4 surgical specimens from 53 patients. IL13Rα2 expression was quantified by H-score calculated from staining intensity and percentage of positive cells. Results: Binding affinity assay of YYB-103 verified apparently nil binding to IL13Rα1, which was more selective than previously reported IL13 modification (E13Y). YYB-103 CAR T cells showed selective toxicity toward co-cultured U87MG (IL13Rα1+/IL13Rα2+) cells but not A431 (IL13Rα1+/IL13Rα2-) cells. Consistently, YYB-103 CAR T cells suppressed tumor growth in nude mice receiving orthotopic injection of U87 MG cells. Both i.c.v. and i.v. injections of YYB-103 CAR T cells reduced tumor volume and prolonged overall survival of tumor-bearing mice. The median H-score for IL13Rα2 in patient-derived MG tissue was 5 (mean, 57.5; SD, 87.2; range, 0 to 300). Conclusion: This preclinical study demonstrates the efficacy of IL13Rα2-targeted YYB-103 CAR T cells against MG cells. The use of modified IL13 to construct a CAR facilitated the selective targeting of IL13Rα2-expressing MG cells while sparing IL13Rα1-expressing cells. Notably, YYB-103 CAR T cells exhibited effective blood-brain barrier crossing, suggesting compatibility with i.v. administration rather than intracranial injection. Additionally, the high H-score for IL13Rα2 in glioblastoma, especially in conjunction with the poor prognostic markers of wild-type isocitrate dehydrogenase-1 (IDH-1) and unmethylated O6-methyl guanine methyl-transferase (MGMT), could be used to determine the eligibility of patients with recurrent glioblastoma for a future clinical trial of YYB-103 CAR T cells.

Practical Model for Energy Consumption Analysis of Omnidirectional Mobile Robot.

The four-wheeled Mecanum robot is widely used in various industries due to its maneuverability and strong load capacity, which is suitable for performing precise transportation tasks in a narrow environment. While the Mecanum wheel robot has mobility, it also consumes more energy than ordinary robots. The power consumed by the Mecanum wheel mobile robot varies enormously depending on their operating regimes and environments. Therefore, only knowing the working environment of the robot and the accurate power consumption model can we accurately predict the power consumption of the robot. In order to increase the applicable scenarios of energy consumption modeling for Mecanum wheel robots and improve the accuracy of energy consumption modeling, this paper focuses on various factors that affect the energy consumption of the Mecanum wheel robot, such as motor temperature, terrain, the center of gravity position, etc. The model is derived from the kinematic and kinetic model combined with electrical engineering and energy flow principles. The model has been simulated in MATLAB and experimentally validated with the four-wheeled Mecanum robot platform in our lab. Experimental results show that the accuracy of the model reached 95%. The results of energy consumption modeling can help robots save energy by helping them to perform rational path planning and task planning.

Feature Preserving Autofocus Algorithm for Phase Error Correction of SAR Images.

Autofocus is an essential technique for airborne synthetic aperture radar (SAR) imaging to correct phase errors mainly due to unexpected motion error. There are several well-known conventional autofocus methods such as phase gradient autofocus (PGA) and minimum entropy (ME). Although these methods are still widely used for various SAR applications, each method has drawbacks such as limited bandwidth of estimation, low convergence rate, huge computation burden, etc. In this paper, feature preserving autofocus (FPA) algorithm is newly proposed. The algorithm is based on the minimization of the cost function containing a regularization term. The algorithm is designed for postprocessing purpose, which is different from the existing regularization-based algorithms such as sparsity-driven autofocus (SDA). This difference makes the proposed method far more straightforward and efficient than those existing algorithms. The experimental results show that the proposed algorithm achieves better performance, convergence, and robustness than the existing postprocessing autofocus algorithms.

PTEN drives Th17 cell differentiation by preventing IL-2 production.

T helper 17 (Th17) cells are a CD4+ T cell subset that produces IL-17A to mediate inflammation and autoimmunity. IL-2 inhibits Th17 cell differentiation. However, the mechanism by which IL-2 is suppressed during Th17 cell differentiation remains unclear. Here, we show that phosphatase and tensin homologue (PTEN) is a key factor that regulates Th17 cell differentiation by suppressing IL-2 production. Th17-specific Pten deletion (Ptenfl/flIl17acre ) impairs Th17 cell differentiation in vitro and ameliorated symptoms of experimental autoimmune encephalomyelitis (EAE), a model of Th17-mediated autoimmune disease. Mechanistically, Pten deficiency up-regulates IL-2 and phosphorylation of STAT5, but reduces STAT3 phosphorylation, thereby inhibiting Th17 cell differentiation. PTEN inhibitors block Th17 cell differentiation in vitro and in the EAE model. Thus, PTEN plays a key role in Th17 cell differentiation by blocking IL-2 expression.

Casein kinase 2 is a critical determinant of the balance of Th17 and Treg cell differentiation.

Th17 cells promote inflammatory reactions, whereas regulatory T (Treg) cells inhibit them. Thus, the Th17/Treg cell balance is critically important in inflammatory diseases. However, the molecular mechanisms underlying this balance are unclear. Here, we demonstrate that casein kinase 2 (CK2) is a critical determinant of the Th17/Treg cell balance. Both the inhibition of CK2 with a specific pharmacological inhibitor, CX-4945, and its small hairpin RNA (shRNA)-mediated knockdown suppressed Th17 cell differentiation but reciprocally induced Treg cell differentiation in vitro. Moreover, CX-4945 ameliorated the symptoms of experimental autoimmune encephalomyelitis and reduced Th17 cell infiltration into the central nervous system. Mechanistically, CX-4945 inhibited the IL-6/STAT3 and Akt/mTOR signaling pathways. Thus, CK2 has a crucial role in regulating the Th17/Treg balance.

Usefulness of titanium mesh cage for posterior C1-C2 fixation in patients with atlantoaxial instability.

The aim of this study was to investigate the usefulness of titanium mesh cage as an interlaminar spacer combined with nitinol shape memory loop fixation in patients with atlantoaxial instability.From April 2009 to March 2017, among the patients with atlantoaxial instability, a total of 30 patients were treated by nitinol shape memory loop fixation combined with titanium mesh cage as a spacer. We retrospectively reviewed 30 enrolled patients. Successful fusion was determined as improvement of symptoms and radiologic findings of bone fusion. We also reviewed surgical complications, instrumentation failure, bony fusion rate, and posterior atlantodental interval (PADI).After surgery, the symptoms of all patients significantly improved. Successful fusion was documented throughout the follow-up period. Evidence of solid bridging bone was found, and no instability was seen on flexion-extension radiographs and callus formation on 3D cervical spine computed tomography (CT) 6 months postoperatively in all cases. No surgical complications were observed. No cases of instrumentation failure were observed. The mean PADI also improved significantly to 22.45 ±â€Š1.11 mm 6 months postoperatively compared with the preoperative value of 18.37 ±â€Š1.16 mm (P < .05).We obtained a good fusion rate by using titanium mesh cage spacer with nitinol shape memory alloy loop in patients with atlantoaxial instability. This technique can help surgeons in avoiding vertebral artery injury and reducing bleeding and operation time. Therefore, we suggest that titanium mesh cage spacer combined with nitinol shape memory alloy loop can be a good substitute of autograft for C1-C2 fusion in treating atlantoaxial instabilities.

Minimally Invasive Esophagectomy Provides Equivalent Survival to Open Esophagectomy: An Analysis of the National Cancer Database.

The use of minimally invasive esophagectomy (MIE) is increasing despite limited evidence to support its efficacy. We compared overall survival and perioperative mortality for MIE vs open esophagectomy (OE). We queried the National Cancer Database for all patients having esophagectomy as the primary procedure for primary squamous cell cancer and adenocarcinoma from 2010 through 2012. A propensity score analysis was performed. Postoperative pathology and quality, as well as overall patient survival outcomes, were compared between OE and MIE. The use of MIE increased from 26.9% in 2010 to 36.3% in 2012 (P < 0.001). Of 3032 patients (2050 OE and 982 MIE) who were identified, propensity score matching (1:1) yielded 977 patients in each group. Mean lymph nodes examined were higher in the MIE group (16.3 vs 14.5, P < 0.001). However, final pathologic nodal stage was not significantly different in the matched sample. There was also no difference in pathologic upstaging or margin status between the groups. All other postoperative variables were equivalent, including an average length of stay of 14 days, unplanned readmission rate of 6.5%, and 30-day and 90-day mortality rates of 3% and 7%, respectively. There was no survival difference, with a median survival of 48.7 months for OE and 46.6 months for MIE (Kaplan-Meier analysis, P = 0.376). During the 3-year period analyzed, there were no significant differences in postoperative outcomes and quality metrics between OE and MIE. Although short-term outcomes are limited in the National Cancer Database, MIE appears to have equivalent oncological outcomes and survival when compared with the open approach.

Increased Prevalence of Ossification of Posterior Longitudinal Ligament and Increased Bone Mineral Density in Patients with Ossification of Nuchal Ligament.

OBJECTIVE: There are also few studies demonstrating the relationship between ossification of nuchal ligament (ONL) and ossification of posterior longitudinal ligament (OPLL). We compared the prevalence, location, and type of OPLL between patients with ONL and matched patients without ONL.We also compared the bone mineral densities (BMDs) between the 2 groups. METHODS: total of 124 cervical ONL patients were enrolled in this study. The control group of 124 patients was matched with 124 patients with ONL by age and sex on a 1:1 basis to minimize confounding factors. We reviewed the prevalence, location, and type of OPLL in both groups. RESULTS: The prevalence of OPLL was almost 2.5 times greater in patients with ONL than those without ONL. The mean value of BMD in patients with ONL was greater at the lumbar spine (L1-L4) than in patients without ONL. The mean T score of the lumbar spine was 0.25±1.68 in the patients with ONL and -0.73±1.64 in the patients without ONL. CONCLUSION: The prevalence of OPLL in patients with ONL was significantly higher than in patients without ONL. Because ONL is innocuous and may be seen more readily than OPLL on simple cervical radiographs, clinicians should consider the possibility of coexisting OPLL when ONL, especially extensive ONL, is detected in patients with neck pain, radiculopathy, or myelopathy, to facilitate proper treatment.

Transcription Factors Oct-1 and GATA-3 Cooperatively Regulate Th2 Cytokine Gene Expression via the RHS5 within the Th2 Locus Control Region.

The T helper type 2 (Th2) locus control region (LCR) regulates Th2 cell differentiation. Several transcription factors bind to the LCR to modulate the expression of Th2 cytokine genes, but the molecular mechanisms behind Th2 cytokine gene regulation are incompletely understood. Here, we used database analysis and an oligonucleotide competition/electrophoretic mobility shift assays to search for transcription factors binding to RHS5, a DNase I hypersensitive site (DHS) within the Th2 LCR. Consequently, we demonstrated that GATA-binding protein-3 (GATA-3), E26 transformation-specific protein 1 (Ets-1), octamer transcription factor-1 (Oct-1), and Oct-2 selectively associate with RHS5. Furthermore, chromatin immunoprecipitation and luciferase reporter assays showed that Oct-1 and Oct-2 bound within the Il4 promoter region and the Th2 LCR, and that Oct-1 and GATA-3 or Oct-2 synergistically triggered the transactivational activity of the Il4 promoter through RHS5. These results suggest that Oct-1 and GATA-3/Oct-2 direct Th2 cytokine gene expression in a cooperative manner.

YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity.

Regulatory T (T(reg)) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for T(reg)-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in T(reg) cells than T(conv) cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of Treg cells. YY1 is increased in T(reg) cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of T(reg) cells by blocking Foxp3.

Cyclo(Phe-Pro) produced by the human pathogen Vibrio vulnificus inhibits host innate immune responses through the NF-κB pathway.

Cyclo(Phe-Pro) (cFP) is a secondary metabolite produced by certain bacteria and fungi. Although recent studies highlight the role of cFP in cell-to-cell communication by bacteria, its role in the context of the host immune response is poorly understood. In this study, we investigated the role of cFP produced by the human pathogen Vibrio vulnificus in the modulation of innate immune responses toward the pathogen. cFP suppressed the production of proinflammatory cytokines, nitric oxide, and reactive oxygen species in a lipopolysaccharide (LPS)-stimulated monocyte/macrophage cell line and in bone marrow-derived macrophages. Specifically, cFP inhibited inhibitory κB (IκB) kinase (IKK) phosphorylation, IκBα degradation, and nuclear factor κB (NF-κB) translocation to the cell nucleus, indicating that cFP affects the NF-κB pathway. We searched for genes that are responsible for cFP production in V. vulnificus and identified VVMO6_03017 as a causative gene. A deletion of VVMO6_03017 diminished cFP production and decreased virulence in subcutaneously inoculated mice. In summary, cFP produced by V. vulnificus actively suppresses the innate immune responses of the host, thereby facilitating its survival and propagation in the host environment.

Venous free flaps for the treatment of skin cancers of the digits.

Microvascular reconstruction using distant free flaps is often required after excision of skin cancers of the digits. The delivered flaps should be chosen with many factors taken into consideration, especially in the digits, in which a very thin, pliable, and durable flap is required to maintain both function and cosmetic appearance. Free flaps, such as perforator flaps, however, for distal or small defects of the hand after excision of skin cancer, require the sacrifices of the main arterial pedicle with deep dissection and exhibit potential limitations regarding flap size and location of the defect. Instead, arterialized venous free flap could be used as an alternative reconstructive method for skin cancers of the digits. Twelve soft tissue defects of the digits after excision of skin cancers (5 cases of malignant melanoma and 7 cases of squamous cell carcinoma) were reconstructed using arterialized venous free flaps from January 2009 to May 2011. The flaps ranged in size from 1 × 1.5 cm to 5 × 7 cm. The flaps completely survived in 9 cases. Partial necrosis developed in 3 cases; however, skin graft was necessary only for 1 case. There were no recurrences or metastases for at least 20 months after the last case. Recently in cases of noninvasive or low-grade skin cancer of the hand, the concept of "preservative surgery" has been a higher priority compared with functional and esthetic aspects. Particularly in cases of reconstruction of a small-sized fingertip defect as 1 functional unit, arterialized venous free flaps offer several advantages, such as thinness and color similar to the hand, technical ease with a short operative time, long vascular pedicle, less donor site morbidity with no sacrifice of a major vessel, applicable to any site, and modifiable to the appropriate size and shape. Arterialized venous free flap could serve as a useful and reliable method for soft tissue reconstruction after excision of skin cancers in the digits.

Cerebral infarction presenting with unilateral isolated foot drop.

Weakness of the dorsiflexor muscles of the ankle or toe, referred to as foot drop, is a relatively common presentation. In most cases, foot drop is caused by a lower motor neuron disease such as peroneal peripheral neuropathy, L4-5 radiculopathic sciatic neuropathy, or polyneuropathy. Although upper motor neuron lesions can present as foot drop, the incidence is very rare. Here, we report an extremely rare case in which foot drop was the only presenting symptom of cerebral infarction.

Effectiveness of autologous serum as an alternative to fetal bovine serum in adipose-derived stem cell engineering.

In cell culture, medium supplemented with fetal bovine serum is commonly used, and it is widely known that fetal bovine serum supplies an adequate environment for culture and differentiation of stem cells. Nevertheless, the use of xenogeneic serum can cause several problems. We compared the effects of four different concentrations of autologous serum (1, 2, 5, and 10%) on expansion and adipogenic differentiation of adipose-derived stem cells using 10% fetal bovine serum as a control. The stem cells were grafted on nude mice and the in vivo differentiation capacity was evaluated. The isolation of adipose-derived stem cells was successful irrespective of the culture medium. The proliferation potential was statistically significant at passage 2, as follows: 10% autologous serum > 10% fetal bovine serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. The differentiation capacity appeared statistically significant at passage 4, as follows: 10% fetal bovine serum > 10% autologous serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. Ten percent autologous serum and 10% fetal bovine serum had greater differentiation capacity than 1 and 2% autologous serum in vivo, and no significant difference was observed between the groups at ≥ 5% concentration at 14 weeks. In conclusion, 10% autologous serum was at least as effective as 10% fetal bovine serum with respect to the number of adipose-derived stem cells at the end of both isolation and expansion, whereas 1 and 2% autologous serum was inferior.

Aberrant expression of IFN-γ in Th2 cells from Th2 LCR-deficient mice.

The Th2 locus control region (LCR) has been shown to be a crucial cis-acting element for Th2 cytokine expression and Th2 cell differentiation. To study the role of Th2 LCR in ifng locus regulation, we examined the expression of IFN-γ in Th2 cells from Th2 LCR-deficient mice. We found IFN-γ to be aberrantly up-regulated. In addition, histone 3(H3)-acetylation and histone 3 lysine 4 (H3-K4)-methylation greatly increased at the ifng locus of the Th2 cells. GATA-3 and STAT6 bound to the ifng promoter in Th2 cells from the wild type but not from the Th2 LCR-deficient mice, and they directly repressed ifng expression in transient reporter assay. Moreover, ectopic expression of GATA-3 and STAT6-VT repressed the aberrant expression of the ifng gene and restored repressive chromatin state at the ifng locus in Th2 cells from Th2 LCR-deficient mice. These results suggest that expression of the ifng gene and chromatin remodeling of the ifng locus are under the control of a Th2 LCR-mediated Th2 differentiation program.

Defective GATA-3 expression in Th2 LCR-deficient mice.

Th2 cell differentiation is critically influenced by transcription factor GATA-3 and by various cis-acting elements including enhancers, silencers and a locus control region (LCR) in the Th2 cytokine locus. Th2 LCR-deficient Th2 cells completely lost the expression of GATA-3 and the phosphorylation of STAT6. Histone 3 lysine 4 (H3-K4) was hypomethylated in the gata3 locus in these cells. GATA-3 and STAT6 bound several regulatory regions in the gata3 locus and transactivated the expression of the gata3 gene. These results suggest that Th2 differentiation program stimulates feed-forward regulation of gata3 gene expression.

Global gene expression analysis on the target genes of PQS and HHQ in J774A.1 monocyte/macrophage cells.

We have previously shown that PQS and HHQ, two quorum sensing molecules, can down-regulate host the innate immune responses and that this is mediated through the NF-kappaB pathway. In this study, to search for a comprehensive set of genes regulated by these quorum sensing molecules, we performed a global gene expression analysis using DNA microarray in J774A.1 monocyte/macrophage cells line. The expression of these genes was confirmed by RT-PCR. We found that PQS and HHQ down-regulated the expression of genes involved in immune responses and transcription as well as other functions, some of which are downstream of NF-kappaB pathway consistent with our previous results. PQS and HHQ inhibited LPS-induced morphological change and nitric oxide production, suggesting that they inhibit macrophage activation. However, PQS and HHQ did not affect apoptosis, suggesting that their effects on immune system are not from general alteration of cell function. This study provides insight how the quorum sensing molecules influence host cells.

HHQ and PQS, two Pseudomonas aeruginosa quorum-sensing molecules, down-regulate the innate immune responses through the nuclear factor-kappaB pathway.

To explore whether bacterial secreted 4-hydroxy-2-alkylquinolines (HAQs) can regulate host innate immune responses, we used the extracts of bacterial culture supernatants from a wild-type (PA14) and two mutants of Pseudomonas aeruginosa that have defects in making HAQs. Surprisingly, the extract of supernatants from the P. aeruginosa pqsA mutant that does not make HAQs showed strong stimulating activity for the production of innate cytokines such as tumour necrosis factor-alpha and interleukin-6 in the J774A.1 mouse monocyte/macrophage cell line, whereas the extract from the wild-type did not. The addition of 4-hydroxy-2-heptylquinoline (HHQ) or 2-heptyl-3,4-dihydroxyquinoline (PQS, Pseudomonas quinolone signal) to mammalian cell culture media abolished this stimulating activity of the extracts of supernatants from the pqsA mutant on the expression of innate cytokines in J774A.1 cells and in the primary bronchoalveolar lavage cells from C57BL/6 mice, suggesting that HHQ and PQS can suppress the host innate immune responses. The pqsA mutant showed reduced dissemination in the lung tissue compared with the wild-type strain in a mouse in vivo intranasal infection model, suggesting that HHQ and PQS may play a role in the pathogenicity of P. aeruginosa. HHQ and PQS reduced the nuclear factor-kappaB (NF-kappaB) binding to its binding sites and the expression of NF-kappaB target genes, and PQS delayed inhibitor of kappaB degradation, indicating that the effect of HHQ and PQS was mediated through the NF-kappaB pathway. Our results suggest that HHQ and PQS produced by P. aeruginosa actively suppress host innate immune responses.

TGF-beta1 represses activation and resultant death of microglia via inhibition of phosphatidylinositol 3-kinase activity.

Overactivation of microglial cells may cause severe brain tissue damage in various neurodegenerative diseases. Therefore, the overactivation of microglia should be repressed by any means. The present study investigated the potential mechanism and signaling pathway for the repressive effect of TGF-beta1, a major anti-inflammatory cytokine, on overactivation and resultant death of microglial cells. A bacterial endotoxin LPS stimulated expression of inducible NO synthase (iNOS) and caused death in cultured microglial cells. TGF-beta1 markedly blocked these LPS effects. However, the LPS-evoked death of microglial cells was not solely attributed to excess production of NO. Because phosphatidylinositol 3-kinase (PI3K) was previously shown to play a crucial role in iNOS expression and cell survival signals, we further studied whether PI3K signaling was associated with the suppressive effect of TGF-beta1. Like TGF-beta1, the PI3K inhibitor LY294002 blocked iNOS expression and death in cultured microglial cells. Both TGF-beta1 and LY294002 decreased the activation of caspases 3 and 11 and the mRNA expression of various kinds of inflammatory molecules caused by LPS. TGF-beta1 was further found to decrease LPS-induced activation of PI3K and Akt. TGF-beta1 and LY294002 suppressed LPS-induced p38 mitogen-activated kinase and c-Jun N-terminal kinase activity. In contrast, TGF-beta1 and LY294002 enhanced LPS-induced NF-kappaB activity. Our data indicate that TGF-beta1 protect normal or damaged brain tissue by repressing overactivation of microglial cells via inhibition of PI3K and its downstream signaling molecules.

The significance of elevated levels of parathyroid hormone in patients with morbid obesity before and after bariatric surgery.

HYPOTHESIS: The risk of hyperparathyroidism after the duodenal switch operation is related to the length of the common channel. DESIGN: A retrospective analysis of patients following the duodenal switch operation from October 2, 2000, through February 1, 2002. SETTING: Academic tertiary referral hospital. PATIENTS: One hundred sixty-five consecutive patients underwent the duodenal switch operation, performed for morbid obesity, with common channel lengths of 75 cm (n = 103 [group A]) and 100 cm (n = 62 [group B]). MAIN OUTCOME MEASURES: Weight loss and parathyroid hormone, corrected calcium, and 25-hydroxyvitamin D (25-OH D) levels were compared between groups A and B. Values were determined preoperatively, early postoperatively (3-6 months), and late postoperatively (9-18 months). RESULTS: Both groups exhibited a slight reduction in serum calcium concentration, with one quarter decreasing below the normal range. Hyperparathyroidism was more common in group A than group B preoperatively (38.9% vs 14.9%), reflecting the higher body mass index of patients in group A. Hyperparathyroidism was also more frequent in the early (54.9% vs 30.9%) and late (49.4% vs 20.5%) postoperative periods in group A vs group B. New-onset hyperparathyroidism was also more common in group A than group B (42.0% vs 13.3%). After 1 year, subnormal 25-OH D levels were found in 17.0% of the patients in group A and in 10.0% of the patients in group B. Median 25-OH D levels increased in both groups, but tended to be higher in group B. CONCLUSIONS: Patients with shorter common channels had a higher risk of developing hyperparathyroidism. This may be related to limited 25-OH D absorption.