Impact of turbulent blood flow in the aortic root on de novo aortic insufficiency during continuous-flow left ventricular-assist device support

Severe aortic insufficiency (AI) after implantation of continuous-flow left ventricular-assist device (LVAD) affects device performance and outcomes. However, the mechanism for the occurrence and progression of AI has not been elucidated. We investigated the impact of nonphysiological retrograde blood flow in the aortic root on AI after LVAD implantation. Blood flow pattern was analyzed in patients with and without AI (n = 3 each) who underwent LVAD implantation, by computational fluid dynamics with patient-specific geometries, which were reproduced using electrocardiogram-gated 320-slice computed tomographic images. The total volume of retrograde blood flow during one cardiac cycle (716 ± 88 mL) was higher and the volume of slow blood flow (<0.1 cm/s) (0.16 ± 0.04 cm³) was lower in patients with AI than in those without AI (360 ± 111 mL, P = .0495, and 0.49 ± 0.08 cm³, P = .0495, respectively). No significant difference in wall shear stress on the aortic valve was observed between the groups. Patients with AI had a perpendicular anastomosis at the distal ascending aorta and the simulation in the modified anastomosis model of patients with AI showed that the retrograde blood flow pattern depended on the angle and position of anastomosis. Computational fluid dynamics revealed strong retrograde blood flow in the ascending aorta and aortic root in patients with AI after LVAD implantation. The angle and position of LVAD outflow anastomosis might impact retrograde blood flow and de novo AI after LVAD implantation.     

Effect of wrist position on distal radioulnar joint stability: A biomechanical study

We investigated distal radioulnar joint (DRUJ) stability in different wrist positions and examined the relative contribution of each ligamentous component of the triangular fibrocartilage complex (TFCC) to DRUJ stability. We used nine fresh‐frozen cadavers. The humerus and ulna were fixed at 90° elbow flexion. The radiocarpal unit was translated relative to the ulna in dorsopalmar directions with the wrist in five positions. Displacement of the unit was measured by an electromagnetic tracking device. Magnitudes of displacement were compared between different wrist positions in various sectioning stages: ulnocarpal ligament (UCL) sectioning, radioulnar ligaments (RUL) sectioning, and extensor carpi ulnaris (ECU) floor sectioning. Wrist position and sectioning stage significantly influenced the displacement. In intact wrists, the displacement in wrist extension was significantly lower than that in neutral. However, after UCL sectioning, there were no longer any significant differences. After RUL sectioning, the displacement in radial deviation was significantly lower than that in neutral. Following ECU floor sectioning, there were no longer any significant differences. Thus, in intact wrists, DRUJ stability in wrist extension is likely due to tightening of the UCL. After complete RUL sectioning, DRUJ is stabilized in radial deviation due to tightening of the ECU floor. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1247–1251, 2014.     

Three-dimensional computed tomography analysis of variations in the middle hepatic vein tributaries: proposed new classification

Purpose

To evaluate the anatomical variations in the middle hepatic vein tributaries (V5/V8) for determining the reconstruction strategy in right lobe living donor liver transplantation (LDLT).

Methods

The V5/V8 variations were examined in 268 patients and were classified into three and two types, respectively. The reconstruction rate (RR), patency rate (PR) and clinical outcomes were retrospectively evaluated in 46 right lobe LDLT cases.

Results

In terms of V5 variations, the RR and PR were significantly higher for type 2 than type 3 (82.6 vs. 44.4 % and 73.7 vs. 25.0 %, respectively). The alanine aminotransferase level on postoperative day (POD) 5 in the V5 patent group was significantly lower than in the occluded group (123 vs. 191 IU/dL). Regarding V8 variations, the RR and PR were significantly higher for type 1 than type 2 (44.4 vs. 17.6 % and 75.0 vs. 33.3 %, respectively). The aspartate aminotransferase level on POD 3 was significantly lower in the V8 patent group than in the occluded group (50 vs. 121 IU/dL).

Conclusion

For right lobe grafts with single large V5 (type 2) or V8 (type 1) variations, reconstruction is necessary. Our new classification of the MHV tributaries is useful for determining the reconstruction strategy to use in right lobe LDLT.     

Comparison of scapholunate distance measurements on plain radiography and computed tomography for the diagnosis of scapholunate instability associated with distal radius fracture

Purpose

To investigate radiographic criteria for scapholunate instability (SLI) in the setting of distal radius fracture (DRF) confirmed by arthroscopy.

Methods

Eighty-eight wrists with DRF treated by open reduction and internal fixation and assessed for SLI arthroscopically were evaluated. The scapholunate distance (SLD) was measured by preoperative posteroanterior wrist radiography and computed tomography (CT). SLD on radiographs was measured as the distance between the scaphoid cortex and the lunate cortex at the center of the scapholunate joint. SLDs were measured at the volar end (A1), center (A2), and dorsal end (A3) of the scapholunate joint on the central CT axial slice; and at the proximal end (C1), center (C2), and distal end (C3) of the scapholunate joint on the central CT coronal slice. Wrists were divided into three groups by arthroscopic assessments: stable (normal, Geissler grade 1 or 2), G3 (Geissler grade 3), and G4 (Geissler grade 4). SLD measurements on radiographs and CTs (A1–C3) were compared among the three groups. Receiver-operating characteristic (ROC) curve analyses were performed to evaluate the abilities of SLD measurements on radiographs and CTs to identify SLI in wrists with DRF. Interobserver and intraobserver reliabilities of SLD measurements on radiographs and CTs were analyzed by intraclass correlation coefficients (ICCs).

Results

SLDs of C3 differed significantly among the G3 and G4 groups, and among the stable and G4 groups. The area under the curve on ROC curve analysis was 0.855 for the SLD of C3, which was larger than that for SLD on radiographs. For C3, the intraobserver ICC was 0.832 and interobserver ICC was 0.73.

Conclusions

SLD at the distal end of the scapholunate joint on the central coronal CT slice was the most appropriate measurement for discrimination of Geissler grade 4 SLI in wrists with DRF.

Level of evidence

Level 2     

Lamotrigine for intractable migraine-like headaches in Sturge–Weber syndrome

We herein report that naratriptan remarkably improved intractable migraine-like headaches in a patient with Sturge–Weber syndrome (SWS) despite his past history of cerebral infarction. In addition, lamotrigine had a prophylactic effect on his visual aura and headaches. An 18-year-old male patient with SWS had intractable migraine-like headaches every several months from the age of 3 years. His migraine-like headaches were characterized by pulsating attacks preceded by left homonymous hemianopsia, which persisted after headache disappearance. In addition, after 14 years of age, the pulsating headaches were preceded by photophobia without homonymous hemianopsia and occurred almost daily. Headache pains were not improved by acetaminophen or loxoprofen sodium hydrate. Furthermore, various prophylactic drugs were ineffective. After obtaining informed consent, naratriptan was administered. The pain severity was reduced and the duration of headache with homonymous hemianopsia was shortened from several days to several hours. Interestingly, naratriptan also shortened the duration of homonymous hemianopsia to several hours. We confirmed that his headache attacks were not epileptic seizures by ictal electroencephalography. However, 25 mg/day of lamotrigine had a prophylactic effect on the frequency of headache. Moreover, lamotrigine led to complete remission of his headache without homonymous hemianopsia. Lamotrigine may have an advantage in terms of reducing the risk of cerebrovascular disease caused by migraine-like headaches and the use of triptans. The most effective management for migraine-like headaches in patients with SWS has not been established. Lamotrigine is a potentially effective option for patients with SWS with migraine-like headaches.     

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.     

Beta-blocker stress echocardiography in an aortic stenosis patient with associated left ventricular outflow tract obstruction

An 80-year-old man visited our hospital because of dyspnea on exertion from 6 months ago. Echo Doppler study showed severe calcification in the aortic valve with restricted movement and the sigmoid septum causing obstruction at the LV outflow tract (LVOT). Considering the aortic valve area (AVA) might have been inaccurately estimated, we carried out beta-blocker stress echocardiography. The transaortic pressure gradient and AVA were respectively calculated as 52 mmHg and 0.90 cm² before propranolol administration and as 64 mmHg and 0.86 cm² after propranolol administration. Thus, beta-blocker stress echocardiography may provide an accurate assessment of AS if the LVOT obstruction is concomitant.     

Interaction of magnesium oxide with gastric acid secretion inhibitors in clinical pharmacotherapy

Purpose

Magnesium oxide (MgO), a short-term osmotic laxative, is converted into MgCl₂ under acidic condition in the stomach and then Mg(HCO₃)₂ in the intestinal tract, where Mg(HCO₃)₂ induces the water exudation into the intestine. This indicates that the laxative effect of MgO could be attenuated under the suppressed gastric acid secretion. In this study, the possible interaction of MgO with gastric acid secretion inhibitors was evaluated by using electronic patient records of MgO dosage levels.

Methods

Defecation was controlled with MgO alone in some patients after colon surgery (n?=?67) and after total gastric resection (n?=?4). Some other patients were treated with a combination use of MgO and H₂ receptor antagonist (H₂RA) (n?=?14) or proton pump inhibitor (PPI) (n?=?27). The possible drug interaction of MgO with H₂RA or PPI was evaluated by comparing dosage levels of MgO used in controlling defecation.

Results

In controlling defecation, the daily dosage levels of MgO in patients taking H₂RA or PPI and patients with total gastric resection were significantly higher than those patients taking MgO alone after colon surgery. The ratios of good constipation control (controlled well at the dosing level of 1,000 mg MgO) in patients taking H₂RA or PPI were significantly lower than that in patients treated with MgO alone. In an in vitro study, the solubility of MgO at pH 4.5 was quite low, as compared with that at pH 1.2.

Conclusions

When patients received H₂RA or PPI, the laxative effect of MgO is decreased possibly due to the low solubility of MgO at the higher gastric pH and less generation of MgCl₂ and Mg(HCO₃)₂. Higher dosing level of MgO or another laxative should be used in patients taking H₂RA or PPI, as well as the case of patients with total gastric resection.