Relationship between cervical and global sagittal balance in patients with dropped head syndrome

DHS is characterized by chin-on-chest deformity and devastatingly impedes activities of daily living in affected individuals. There is a paucity of literature about the pathophysiology of DHS including knowledge about spinal sagittal alignment. We conducted this study to clarify the relationship between cervical sagittal alignment and global sagittal balance in DHS. This is a retrospective radiographic study of a case series of DHS. Forty-one patients with diagnosed DHS were enrolled. Measurements were made using lateral standing radiograph. C2–C7 sagittal vertical axis (SVA) was estimated as 52.0 ± 2.4 mm. Among sagittal parameters, C7–S1 SVA positively correlated with C2–C7 angle (C2–C7 A) (r = 0.33). For the correlations between C7 and S1 SVA and C2–C7 A, both logistic and linear regression models were used to determine the threshold for C2–C7 A value responsible for global sagittal balance. C2–C7 A of − 15.0 and 6.0 were predicted by logistic and linear regression models and were considered responsible for the occurrence of global positive imbalance. Therefore, we divided into two groups, namely, cervical kyphosis group (C type) and diffuse kyphosis group (D type) by median value of C2–C7 A. Enlarged thoracic kyphosis and global positive imbalance were observed in D type compared to C type. C2–C7 A exhibited correlations with cervical balance and also with global balance. There should be various type of thoraco-lumbar alignment in DHS. These slides can be retrieved under Electronic Supplementary Material.     

Vocal cord inflammatory myofibroblastic tumor with mucoid deposits harboring TIMP3–ALK fusion: A potential diagnostic pitfall

A 35‐year‐old Japanese man who had experienced hoarseness for 10 years presented with a vocal cord lesion. A gross examination revealed a left vocal cord polyp occupying two‐thirds of the vocal space. The endoscopically resected lesion contained scattered atypical fibroblastic, stellate, or ganglion‐like cells with mucoid stroma. Vacuolated cells were also seen. Lymphoplasmacytic infiltrate was largely undetectable. A vocal cord polyp was first suspected, but well‐differentiated liposarcoma and inflammatory myofibroblastic tumor (IMT) were included in the differential diagnoses. The tumor cells were positive for anaplastic lymphoma kinase (ALK), calponin, and vimentin, and negative for other smooth muscle markers by immunohistochemistry. Structures resembling myofibroblasts were not observed by electron microscopy, which confirmed abundant rough endoplasmic reticulum in the tumor cells and accumulated lipid droplets in some tumor cells. ALK gene rearrangement was detected by fluorescence in situ hybridization, and TIMP3–ALK fusion was confirmed by 5′ rapid ampli?cation of cDNA ends. We diagnosed the lesion as an IMT, and an ALK‐rearranged stellate cell tumor may be postulated. This is the first report of a fusion partner gene of ALK in a case of laryngeal IMT.     

Bartlett‐type corrections and bootstrap adjustments of likelihood‐based inference methods for network meta‐analysis

In network meta‐analyses that synthesize direct and indirect comparison evidence concerning multiple treatments, multivariate random effects models have been routinely used for addressing between‐studies heterogeneities. Although their standard inference methods depend on large sample approximations (eg, restricted maximum likelihood estimation) for the number of trials synthesized, the numbers of trials are often moderate or small. In these situations, standard estimators cannot be expected to behave in accordance with asymptotic theory; in particular, confidence intervals cannot be assumed to exhibit their nominal coverage probabilities (also, the type I error probabilities of the corresponding tests cannot be retained). The invalidity issue may seriously influence the overall conclusions of network meta‐analyses. In this article, we develop several improved inference methods for network meta‐analyses to resolve these problems. We first introduce 2 efficient likelihood‐based inference methods, the likelihood ratio test–based and efficient score test–based methods, in a general framework of network meta‐analysis. Then, to improve the small‐sample inferences, we developed improved higher‐order asymptotic methods using Bartlett‐type corrections and bootstrap adjustment methods. The proposed methods adopt Monte Carlo approaches using parametric bootstraps to effectively circumvent complicated analytical calculations of case‐by‐case analyses and to permit flexible application to various statistical models network meta‐analyses. These methods can also be straightforwardly applied to multivariate meta‐regression analyses and to tests for the evaluation of inconsistency. In numerical evaluations via simulations, the proposed methods generally performed well compared with the ordinary restricted maximum likelihood–based inference method. Applications to 2 network meta‐analysis datasets are provided.     

Role of ascorbic acid in periodontal ligament cell differentiation

BACKGROUND: Periodontal ligament (PDL) cells form mineralized nodules in vitro. Ascorbic acid is known to be required in this process, although its effect on osteoblastic differentiation of PDL cells remains unclear. The purpose of this study was to determine the role of ascorbic acid on the early osteoblastic differentiation of PDL cells, with regard to alkaline phosphatase (ALP) activity, type I collagen production and integrin expression. METHODS: Cultured PDL cells were stimulated at confluence with ascorbic acid in the presence or absence of type I collagen inhibitor and blocking antibodies to integrins. After stimulation, the cells and culture supernatants were examined for ALP activity, type I collagen production, and integrin expression. The ALP activity was measured using a colorimetric assay with p-nitrophenyl phosphate and ALP staining. Enzyme-linked immunosorbent assay (ELISA) was used to determine type I collagen production, and ELISA and flow cytometric analysis were employed for assessment of integrin expression. RESULTS: Both ALP activity and type I collagen production were upregulated when PDL cells were cultured in the presence of ascorbic acid (200 microM). Inhibitor of the formation of collagen triple helices and blocking antibodies to alpha2beta1 integrin inhibited ALP activity by 50% in ascorbic acid-stimulated PDL cells. Furthermore, ascorbic acid increased the cell surface expression of alpha2beta1 integrin. CONCLUSIONS: Our findings indicated that ascorbic acid increases the ALP activity of PDL cells via type I collagen production and also enhances the expression of alpha2beta1 integrin, which is a major receptor of type I collagen. These results suggest that ascorbic acid promotes the osteoblastic differentiation of PDL cells by modulating type I collagen-alpha2beta1 integrin interaction.     

Hand-assisted laparoscopic subtotal colectomy with cecorectal anastomosis for chronic idiopathic colonic pseudo-obstruction: report of a case

Chronic idiopathic colonic pseudo-obstruction (CICP) is characterized by the chronic disturbance of colonic motility without mechanical obstruction, any underlying disease or medication. Currently, there are no established medical treatments for CICP. A 62-year-old female who had undergone right hemicolectomy for splenic flexure syndrome caused by idiopathic megacolon was referred to our hospital with relapse, experiencing palpitation and abdominal fullness. She was diagnosed with CICP according to findings of marked dilation of the colon without mechanical obstruction, dilation of other parts of the gastrointestinal tract, or underlying disease. The dilated colon was surgically removed by hand-assisted laparoscopic subtotal colectomy, followed by cecorectal anastomosis. Histopathologically, there was no degeneration or lack of ganglion cells in Auerbach’s plexus. The patient has experienced no severe symptoms after undergoing the present operation.     

Hepatectomy-Related Hypophosphatemia: A Novel Phosphaturic Factor in the Liver-Kidney Axis

Marked hypophosphatemia is common after major hepatic resection, but the pathophysiologic mechanism remains unknown. We used a partial hepatectomy (PH) rat model to investigate the molecular basis of hypophosphatemia. PH rats exhibited hypophosphatemia and hyperphosphaturia. In renal and intestinal brush-border membrane vesicles isolated from PH rats, Na⁺-dependent phosphate (Pi) uptake decreased by 50%–60%. PH rats also exhibited significantly decreased levels of renal and intestinal Na⁺-dependent Pi transporter proteins (NaPi-IIa [NaPi-4], NaPi-IIb, and NaPi-IIc). Parathyroid hormone was elevated at 6 hours after PH. Hyperphosphaturia persisted, however, even after thyroparathyroidectomy in PH rats. Moreover, DNA microarray data revealed elevated levels of nicotinamide phosphoribosyltransferase (Nampt) mRNA in the kidney after PH, and Nampt protein levels and total NAD concentration increased significantly in the proximal tubules. PH rats also exhibited markedly increased levels of the Nampt substrate, urinary nicotinamide (NAM), and NAM catabolites. In vitro analyses using opossum kidney cells revealed that NAM alone did not affect endogenous NaPi-4 levels. However, in cells overexpressing Nampt, the addition of NAM led to a marked decrease in cell surface expression of NaPi-4 that was blocked by treatment with FK866, a specific Nampt inhibitor. Furthermore, FK866-treated mice showed elevated renal Pi reabsorption and hypophosphaturia. These findings indicate that hepatectomy-induced hypophosphatemia is due to abnormal NAM metabolism, including Nampt activation in renal proximal tubular cells.Inorganic phosphate (Pi) absorption in the renal proximal tubules and small intestine is important for Pi homeostasis.¹ The Na⁺-dependent Pi (Na/Pi) transport system includes type IIa and type IIc Na/Pi transporters, which are localized in the apical membrane of the proximal tubular cells, and type IIb Na/Pi transporters, which are localized in the apical membrane of the intestinal epithelial cells.^1,2 Pi (re)absorption is regulated by the dietary Pi content, parathyroid hormone (PTH), and the active metabolite of vitamin D, 1α, 25-dihydroxyvitamin D3 [1,25(OH)₂D₃].³ Other phosphaturic hormones, termed phosphatonins, also control renal Pi handling.⁴ The discovery that fibroblast growth factor (FGF) 23, the first identified phosphatonin,⁵ originated from osteocytes established the concept of the bone-kidney axis.^6,7The incidence of liver transplantation has steadily increased and the incidence of partial hepatectomy (PH) has also consequently increased.⁸ Hypophosphatemia frequently occurs after liver resection.^9–11 Acute hypophosphatemia causes septicemia and is associated with a poor prognosis.^11,12 Acute hypophosphatemia is of considerable clinical relevance because many hepatectomized patients develop marked hypophosphatemia and, thus, large doses of Pi replacement are required to maintain metabolic homeostasis.¹³ Urinary Pi excretion is markedly increased in many patients. After hepatectomy, hypophosphatemia is associated with hyperphosphaturia.¹³For many years, the increased metabolic demand of the regenerating liver was considered the underlying pathologic mechanism of hypophosphatemia. The magnitude of Pi uptake by the recovering liver, however, cannot explain the severity of the resulting hypophosphatemia.¹¹ Hepatectomy-induced hypophosphatemia is associated with an increased renal fractional excretion index for Pi unrelated to intact FGF23, FGF7, or secreted frizzled-related protein 4 as a phosphaturic factor,¹⁴ indicating that other factors have a role in the pathogenesis of hypophosphatemia.Nicotinamide (NAM) inhibits intestinal and renal Na/Pi transport activity in normal rats.^15–17 Administration of NAM to rats produces a specific dose-dependent inhibition of Na/Pi transport across the renal brush-border membrane (BBM) and an increase in urinary Pi excretion.^16,17 NAM suppresses hyperphosphatemia in hemodialysis patients.¹⁸ Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first rate-limiting step in converting NAM to NAD,^19,20 which is essential for cellular metabolism, energy production, and DNA repair.^20–22 Nampt exists in two known forms: intracellular Nampt (iNampt) and secreted extracellular Nampt (eNampt).²³ eNampt also generates an intermediate product, nicotinamide mononucleotide (NMN).²³Our findings indicate that the acceleration of NAM metabolism through Nampt function in the kidney is involved in the hepatectomy-induced hypophosphatemia in rodent models. This study also suggests that NAM metabolism through the liver-kidney axis is important in Pi homeostasis.