Patterns of coronary artery ectasia and short-term outcome in acute myocardial infarction

Objective. To assess the relationship between hematological inflammatory signs, cardiovascular risk (CV) factors and prognosis in patients presenting with acute myocardial infarction (AMI) and coronary artery ectasia (CAE). Design. We investigated 3321 AMI patients who required urgent primary percutaneous intervention in two centres in the United Kingdom between January 2009 and August 2012. Thirty patients with CAE were compared with 60 age- and gender-matched controls. Blood was collected within 2 h of the onset of chest pain. CV risk factors were assessed from the records. Major acute cardiac events and/or mortality (MACE) over 2 years were documented. Results. CAE occurred in 2.7% and more often affected the right (RCA) (p = 0.001) and left circumflex artery (LCx) (0.0001). Culprit lesions were more frequently related to atherosclerosis in non-CAE patients (p = 0.001). Yet, CV risk factors failed to differentiate between the groups, except diabetes, which was less frequent in CAE (p = 0.02). CRP was higher in CAE (p = 0.006), whereas total leucocyte, neutrophil counts and neutrophil/lymphocyte ratio (N/L ratio) were lower (p = 0.002, 0.002 and 0.032, respectively) than among non-CAE. This also was the case in diffuse versus localised CAE (p = 0.02, 0.008 and 0.03, respectively). The MACE incidence did not differ between CAE and non-CAE (p = 0.083) patients, and clinical management and MACE were unrelated to the inflammatory markers. Conclusion. In AMI, patients with CAE commonly have aneurysmal changes in RCA and LCx, and their inflammatory responses differ from those with non-CAE. These differences did not have prognostic relevance, and do not suggest different management.     

Hip fracture and risk of acute myocardial infarction: A nationwide study

Osteoporotic fractures are associated with increased mortality risk. However, little data are available on the risk of acute myocardial infarction (AMI) after hip fracture. Therefore, we investigated whether hip fracture increased the risk of AMI in a large, nationwide cohort study. We obtained data from 8758 patients diagnosed with hip fracture from 2000 to 2009 and from 4 matched controls for each patient from the Longitudinal Health Insurance Database (LHID 2000), Taiwan. Controls were matched for age, sex, comorbid disorders, and enrollment date. All subjects were followed up from the date of enrollment until AMI, death, or the end of data collection (2009). Cox's regression model adjusted for age, sex, comorbid disorders, and medication was used to assess independent factors determining the risk of development of AMI. As expected, despite the matching, the hip fracture patients had more risk factors for AMI at baseline. A total of 8758 subjects with hip fractures and 35,032 controls were identified. Among these patients, 1183 (257 hip fracture patients and 926 controls) developed AMI during the median 3.2‐year (interquartile range 1.4 to 5.8 years) follow‐up period. Patients with hip fractures had a higher incidence of AMI occurrence when compared with controls (8.7/1000 person‐years versus 6.82/1000 person‐years). Multivariate analysis adjusted for baseline covariates indicated that hip fracture was associated with a greater risk for AMI development (hazard ratio [HR] = 1.29; 95% confidence interval [CI] 1.12–1.48; p < 0.001). We conclude that hip fracture is independently associated with a higher risk of subsequent AMI. © 2013 American Society for Bone and Mineral Research     

Skeletal microstructural abnormalities in postmenopausal women with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is associated with osteoporosis and fragility fractures. The objectives of this study were to assess static and dynamic indices of cancellous and cortical bone structure in postmenopausal women with COPD. Twenty women with COPD who had not received chronic oral glucocorticoids underwent bone biopsies after double tetracycline labeling. Biopsies were analyzed by histomorphometry and µCT and compared with age‐matched controls. Distribution of the patients according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was: Type I (15%), Type II (40%), Type III (30%), and Type IV (15%). Mean (±SD) cancellous bone volume (15.20 ± 5.91 versus 21.34 ± 5.53%, p = .01), trabecular number (1.31 ± 0.26 versus 1.77 ± 0.51/mm, p = .003), and trabecular thickness (141 ± 23 versus 174 ± 36 µm, p = .006) were lower in patients than in controls. Connectivity density was lower in COPD (5.56 ± 2.78 versus 7.94 ± 3.08/mm, p = .04), and correlated negatively with smoking (r = ?0.67; p = .0005). Trabecular separation (785 ± 183 versus 614 ± 136 µm, p = .01) and cortical porosity (4.11 ± 1.02 versus 2.32 ± 0.94 voids/mm²; p < .0001) were higher in COPD while cortical width (458 ± 214 versus 762 ± 240 µm; p < .0001) was lower. Dynamic parameters showed significantly lower mineral apposition rate in COPD (0.56 ± 0.16 versus 0.66 ± 0.12 µm/day; p = .01). Patients with more severe disease, GOLD III and IV, presented lower bone formation rate than GOLD I and II (0.028 ± 0.009 versus 0.016 + 0.011 µm³/µm²/day; p = 04). This is the first evaluation of bone microstructure and remodeling in COPD. The skeletal abnormalities seen in cancellous and cortical bone provide an explanation for the high prevalence of vertebral fractures in this disease. © 2010 American Society for Bone and Mineral Research     

Patients with sclerosteosis and disease carriers: Human models of the effect of sclerostin on bone turnover

Sclerosteosis is a rare bone sclerosing dysplasia, caused by loss‐of‐function mutations in the SOST gene, encoding sclerostin, a negative regulator of bone formation. The purpose of this study was to determine how the lack of sclerostin affects bone turnover in patients with sclerosteosis and to assess whether sclerostin synthesis is decreased in carriers of the SOST mutation and, if so, to what extent this would affect their phenotype and bone formation. We measured sclerostin, procollagen type 1 amino‐terminal propeptide (P1NP), and cross‐linked C‐telopeptide (CTX) in serum of 19 patients with sclerosteosis, 26 heterozygous carriers of the C69T SOST mutation, and 77 healthy controls. Chips of compact bone discarded during routine surgery were also examined from 6 patients and 4 controls. Sclerostin was undetectable in serum of patients but was measurable in all carriers (mean 15.5 pg/mL; 95% confidence interval [CI] 13.7 to 17.2 pg/mL), in whom it was significantly lower than in healthy controls (mean 40.0 pg/mL; 95% CI 36.9 to 42.7 pg/mL; p < 0.001). P1NP levels were highest in patients (mean 153.7 ng/mL; 95% CI 100.5 to 206.9 ng/mL; p = 0.01 versus carriers, p = 0.002 versus controls), but carriers also had significantly higher P1NP levels (mean 58.3 ng/mL; 95% CI 47.0 to 69.6 ng/mL) than controls (mean 37.8 ng/mL; 95% CI 34.9 to 42.0 ng/mL; p = 0.006). In patients and carriers, P1NP levels declined with age, reaching a plateau after the age of 20 years. Serum sclerostin and P1NP were negatively correlated in carriers and age‐ and gender‐matched controls (r = 0.40, p = 0.008). Mean CTX levels were well within the normal range and did not differ between patients and disease carriers after adjusting for age (p = 0.22). Our results provide in vivo evidence of increased bone formation caused by the absence or decreased synthesis of sclerostin in humans. They also suggest that inhibition of sclerostin can be titrated because the decreased sclerostin levels in disease carriers did not lead to any of the symptoms or complications of the disease but had a positive effect on bone mass. Further studies are needed to clarify the role of sclerostin on bone resorption. © 2011 American Society for Bone and Mineral Research     

Preferential Maternal Transmission of STX16-GNAS Mutations Responsible for Autosomal Dominant Pseudohypoparathyroidism Type Ib (PHP1B): Another Example of Transmission Ratio Distortion

Preferential transmission of a genetic mutation to the next generation, referred to as transmission ratio distortion (TRD), is well established for several dominant disorders, but underlying mechanisms remain undefined. Recently, TRD was reported for patients affected by pseudohypoparathyroidism type Ia or pseudopseudohypoparathyroidism. To determine whether TRD is observed also for autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP1B), we analyzed kindreds with the frequent 3-kb STX16 deletion or other STX16/GNAS mutations. If inherited from a female, these genetic defects lead to loss-of-methylation at exon A/B alone or at all three differentially methylated regions (DMR), resulting in parathyroid hormone (PTH)-resistant hypocalcemia and hyperphosphatemia and possibly resistance to other hormones. In total, we investigated 212 children born to 80 females who are unaffected carriers of a STX16/GNAS mutation (n = 47) or affected by PHP1B (n = 33). Of these offspring, 134 (63.2%) had inherited the genetic defect (p = .00012). TRD was indistinguishable for mothers with a STX16/GNAS mutation on their paternal (unaffected carriers) or maternal allele (affected). The mechanisms favoring transmission of the mutant allele remain undefined but are likely to include abnormalities in oocyte maturation. Search for mutations in available descendants of males revealed marginally significant evidence for TRD (p = .038), but these analyses are less reliable because many more offspring of males than females with a STX16/GNAS mutation were lost to follow-up (31 of 98 versus 6 of 218). This difference in follow-up is probably related to the fact that inheritance of a mutation from a male does not have clinical implications, whereas inheritance from an affected or unaffected female results in PHP1B. Lastly, affected PHP1B females had fewer descendants than unaffected carriers, but it remains unclear whether abnormal oocyte development or impaired actions of reproductive hormones are responsible. Our findings highlight previously not recognized aspects of AD-PHP1B that are likely to have implications for genetic testing and counseling. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Heterozygosity for the factor V Leiden (G1691A) mutation predisposes renal transplant recipients to thrombotic complications and graft loss

BACKGROUND: Heterozygosity for a mutation in the coagulation factor V gene (factor V Leiden; FVL) leads to resistance to activated protein C and represents the most common cause of inherited thrombophilia. FVL is associated with a high risk for thromboembolic events and might be a risk factor for venous thrombosis and early graft loss in renal transplant recipients. METHODS: We studied a cohort of 202 renal allograft recipients to assess the impact of the FVL mutation on thrombotic events and graft loss within 1 year after transplantation. We recorded the occurrence of deep venous thrombosis, pulmonary embolism, early graft perfusion defect, and graft loss. The occurrence of these events was then correlated with the presence or absence of heterozygosity for the FVL mutation. RESULTS: Heterozygosity for FVL was detected in 8 (4%) of 202 patients. The incidence of deep venous thrombosis or pulmonary embolism was higher in heterozygous compared with wild-type patients (25% vs. 5.7%, P=0.09). Furthermore, early graft perfusion defect (25% vs. 2.6%; P=0.03) and graft loss within 7 days after transplantation (2/8 vs. 1/194; P=0.004) were significantly more frequent among heterozygous carriers of FVL. All eight FVL carriers were negative for protein C or S deficiency and antiphospholipid and anticardiolipin antibodies, and were not carriers of the G20210A prothrombin mutation. CONCLUSIONS: Heterozygosity for the FVL mutation predisposes renal allograft recipients to venous thromboembolic complications, graft perfusion defects, and early transplant loss. Screening for the FVL mutation and appropriate peri- and postoperative anticoagulation after renal transplantation might prevent these thromboembolic complications.     

Low Plasma Level of Leucine‐Rich Repeat‐Containing 17 (LRRc17) Is an Independent and Additive Risk Factor for Osteoporotic Fractures in Postmenopausal Women

A novel role of leucine‐rich repeat‐containing 17 (LRRc17), an LRR protein secreted by osteoblasts, as a negative regulator of receptor activator of NF‐κB ligand–induced osteoclast differentiation was found. However, the clinical association between LRRc17 and osteoporotic fracture (OF) has not yet been investigated. We hypothesized that low circulating plasma level of LRRc17 might serve as an independent and additive risk factor for OF, including vertebral fractures (VF) and non‐vertebral fractures (non‐VF). In this case‐control study, 102 OF cases and 102 age‐ and body mass index–matched controls (mean age, 63.2 years) were analyzed among 532 postmenopausal women. VF (n = 49) and non‐VF (n = 60) participants were identified using lateral thoracolumbar radiographs and an interviewer‐assisted questionnaire, respectively. Median LRRc17 levels were significantly lower in participants with any OF (117.5 versus 197.3 pg/mL, p < 0.001), VF (93.2 versus 172.4 pg/mL, p = 0.002), and non‐VF (124.5 versus 206.9 pg/mL, p = 0.008) compared with the respective controls without fractures. The prevalence of OF increased from the highest LRRc17 tertile (≥228.5 pg/mL, 33.8%) to the lowest (<95.6 pg/mL, 63.2%). Each log unit decrease of LRRc17 was associated with greater risk of OF (odds ratio [OR] = 1.46; 95% confidence interval [CI] 1.10–1.96; p = 0.009) and VF (OR = 2.42; 95% CI 1.39–4.23; p = 0.002). Plasma LRRc17 significantly improved discrimination of OF, particularly VF, when added to models including clinical risk factors and bone mineral density according to the area under receiver operating characteristics curves (AUC 0.71 to 0.81, p = 0.036), category‐free net reclassification improvement (0.79; 95% CI 0.37–1.21; p < 0.001), and integrated discrimination improvement (0.13; 95% CI 0.06–0.20; p < 0.001). Low plasma LRRc17 was an independent risk factor for OF, which improved risk stratification, particularly in the spines of postmenopausal women. © 2016 American Society for Bone and Mineral Research.     

Factor V Leiden Does Not Affect Bleeding in Aprotinin Recipients after Cardiopulmonary Bypass

Background: Carriers of the factor V Leiden mutation (FVL) are resistant to activated protein C proteolysis. Therefore, they are at increased risk of thromboembolic events. Aprotinin is an unspecific proteinase inhibitor frequently used during cardiac surgery procedures to reduce bleeding. However, aprotinin may cause thromboembolic complications after cardiopulmonary bypass (CPB). The primary endpoint of this study was the amount of blood loss after CPB in aprotinin recipients, and secondary endpoints were thromboembolic complications.

Methods: A total of 1,447 consecutive patients who underwent cardiac surgery with CPB were prospectively enrolled. All patients were screened for FVL by a fluorescence-based polymerase chain reaction method. Linear and logistic regression analyses were performed to assess associations of FVL on bleeding and thromboembolic complications.

Results: One hundred seven individuals (7.4%) were heterozygous FVL carriers. No difference was found between FVL carriers and noncarriers regarding age, sex, CPB, type of operation, EuroSCORE, antiplatelet treatment, and reoperation. FVL was not significantly associated with postoperative blood loss, whereas a significant influence was found for female sex (P < 0.0001), duration of CPB (P < 0.0001), reoperation (P = 0.001), and preoperative antiplatelet treatment (P < 0.002). Multiple linear regression analysis for total blood loss had an observed power of at least 99%. FVL carriers faced the same risk for postoperative transfusion (P = 0.391), reoperation (P = 0.675), myocardial infarction (P = 0.44), stroke (P = 0.701), and 30-day mortality (P = 0.4) as did noncarriers.     

Duodenogastric Reflux after Esophagectomy and Gastric Pull-up: The Effect of the Route of Reconstruction

Duodenogastric reflux (DGR) is a common sequel of subtotal esophagectomy and gastric pull-up, and it may contribute to mucosal changes of both the gastric conduit and the esophageal remnant. This study investigated the effect of the route of reconstruction on the DGR. 24-hour ambulatory bilirubin monitoring was performed on patients who underwent transhiatal subtotal esophagectomy and a gastric tube interposition either in the posterior mediastinum (PM group, n = 11), or in the retrosternal space (RS group, n = 8): A Control group of 8 healthy volunteers was also studied. The median percentage of reflux time, the median number of reflux episodes, and the median number of reflux episodes longer than 5 minutes, in PM versus RS groups, were 29.1% versus 0.15% (p < 0.001), 185 versus 8 (p = 0.002) and 10 versus 0 (p = 0.001), respectively. The values of the above variables in PM versus control groups were 29.1% versus 3.95% (p = 0.007), 185 versus 21 (p = 0.02), and 10 versus 2 (p = 0.009), respectively, whereas in RS versus control groups they were 0.15% versus 3.95% (p = 0.01), 8 versus 21 (p = 0.04), and 0 versus 2 (p = 0.05), respectively. Posterior mediastinal gastric interposition is associated with high reflux of duodenal contents, whereas retrosternal interposition minimizes the reflux at levels even lower than those of the healthy individuals. The latter type of reconstruction may be a good alternative from that perspective, especially in patients with long life expectancy.     

X-Linked Hypophosphatemia: Uniquely Mild Disease Associated With PHEX 3′-UTR Mutation c.*231A>G (A Retrospective Case–Control Study)

X-linked hypophosphatemia (XLH), the most prevalent heritable renal phosphate (Pi) wasting disorder, is caused by deactivating mutations of PHEX. Consequently, circulating phosphatonin FGF23 becomes elevated and hypophosphatemia in affected children leads to rickets with skeletal deformity and reduced linear growth while affected adults suffer from osteomalacia and forms of ectopic mineralization. In 2015, we reported uniquely mild XLH in six children and four of their mothers carrying the non-coding PHEX 3′-UTR mutation c.*231A>G. Herein, we characterize this mild XLH variant by comparing its features in 30 individuals to 30 age- and sex-matched patients with XLH but without the 3′-UTR mutation. The “UTR” and “XLH” groups, both comprising 17 children (2 to 17 years, 3 girls) and 13 adults (23 to 63 years, 10 women), had mean ages of 23 years. Only 43% of the UTR group versus 90% of the XLH group had received medical treatment for their disorder, including 0% versus 85% of the females, respectively (ps < .0001). The UTR group was taller: mean ± SD height Z-score (HZ) −1.0 ± 1.0 versus −2.0 ± 1.4 (p = .0034), with significantly greater height for females (−0.9 ± 0.7 versus −2.3 ± 1.4; p = .0050) but not males (−1.2 ± 1.1 versus −1.9 ± 1.5; p = .1541), respectively. Mean ± SD “arm span Z-score” (AZ) did not differ between the UTR −0.8 ± 1.3 versus XLH −1.3 ± 1.8 groups (p = .2269). Consequently, the UTR group was more proportionate with a mean ∆Z (AZ – HZ) of 0.1 ± 0.6 versus 0.7 ± 1.0 (p = .0158), respectively. Compared to the XLH group, the UTR group had significantly higher fasting serum Pi and renal tubular threshold maximum for phosphorus per glomerular filtration rate (TmP/GFR) (ps ≤ .0060), serum FGF23 concentrations within the reference range (p = .0068), and similar serum alkaline phosphatase levels (p = .6513). UTR lumbar spine bone mineral density Z-score was higher (p = .0343). Thus, the 3′-UTR variant of XLH is distinctly mild, especially in girls and women, posing challenges for its recognition and management. © 2020 American Society for Bone and Mineral Research.     

Bone involvement in aldosteronism

In rats with aldosteronism, a reduction of bone mineral density (BMD) and cortical bone strength has been reported. Our study was aimed to evaluate bone involvement in patients with primary aldosteronism (PA). A total of 188 consecutive subjects with adrenal incidentaloma, observed between November 2009 and October 2011, were screened for PA with aldosterone‐to‐renin ratio. After confirmatory tests, in those who screened positive, 11 patients were diagnosed as PA and 15 patients were not (nPA). A serum/urinary biochemical profile, parathyroid hormone (PTH), BMD measured at lumbar spine (LS) and total and femoral neck (TN and FN) by dual X‐ray absorptiometry, and conventional spinal radiographs (T₄–L₄) were obtained in all subjects. PA patients had a significantly higher 24‐hour urinary calcium (6.28 ± 1.85 versus 4.28 ± 1.18 mmol/d; p < 0.01), and PTH (9.8 [5.8‐14.6], median [range] versus 5.3 [2.5‐10.8] pmol/L; p < 0.01) than nPA patients. BMD expressed as Z‐value at LS (?1.18 ± 0.99 versus 0.22 ± 1.12), FN (?0.85 ± 0.73 versus 0.01 ± 0.82), and TN (?0.49 ± 0.61 versus 0.39 ± 0.93) was lower in PA than in nPA (p = 0.003, p = 0.011, and p = 0.012, respectively). The prevalence of osteoporosis was higher in PA than in nPA (8/11, 72.7% versus 3/15, 20.0%; Fisher's exact test: p = 0.015). Vertebral fractures tended to be more prevalent in PA than in nPA (5/11, 45.5% versus 2/15, 13.3%; Fisher's exact test: p = 0.095). Logistic regression analysis showed that osteoporosis and morphometric vertebral fractures were associated with PA (odds ratio [OR], 15.4; 95% confidence interval [CI] = 1.83–130, p = 0.012; and OR, 30.4; 95%CI, 1.07–862, p = 0.045, respectively) regardless of age, body mass index (BMI), and LS‐BMD. In 9 of 11 PA patients, 6 months after beginning of treatment (surgery or spironolactone) there was a significant reduction of urinary calcium excretion (p < 0.01) and PTH (p < 0.01), whereas in 5 of 11 PA patients, 1 year after beginning of treatment, BMD was significantly increased at LS, p < 0.01). In conclusion, PA is associated with osteoporosis, vertebral fractures, and increased urinary calcium excretion. © 2012 American Society for Bone and Mineral Research.     

A prospective randomized controlled trial of sclerotherapy vs ligation in the prophylactic treatment of high-risk esophageal varices

Background: Endoscopic ligation (EVL) and endoscopic sclerotherapy (EIS) are both effective in the treatment of bleeding esophageal varices, but the efficacy of the two techniques in the prophylaxis of first variceal bleeding has not been investigated. The aim of this study was to investigate the frequency of first variceal bleeding, the recurrence of varices, and survival after treatment with the two techniques, as compared to a nontreated control group. Methods: A total of 157 patients with liver cirrhosis and advanced esophageal varices with no previous history of upper gastrointestinal bleeding were randomly assigned to either an EIS group (n= 55), an EVL group (n= 52), or a nontreated control group (n= 50). After the eradication of esophageal varices in the EIS and in EVL groups and in all control patients, the endoscopic examination was performed at 3-month intervals. Results: There were no significant differences between EIS and EVL in the eradication rate of esophageal varices (85% in the EIS group versus 81% in the EVL group). The mean number of sessions required to obtain eradication was lower in the EVL group than in the EIS group (4.8 ± 1.8 versus 6.2 ± 2.0; p= 0.0003), but the recurrence of esophageal varices was higher in the EVL group (31% versus 11%; p= 0.01). Total mortality was significantly lower in the EIS patients than in the controls (20% versus 38%; p= 0.04). It was also lower, but not significantly, in the EVL patients than in the controls (23% versus 38%; p= 0.10). A significant decrease in variceal bleeding was observed both in sclerotherapy cases (20%) and controls (54%; p= 0.0005) and in ligation cases and controls (29%; p= 0.01). No significant difference in bleeding episodes was observed between the sclerotherapy and ligation cases (p= 0.29). No serious complications were observed either in the EIS or EVL groups. Conclusions: EIS and EVL are similarly effective in the prevention of first variceal bleeding. The choice between EIS and EVL depends on the skill of the endoscopic unit. For highly experienced surgeons facing no complications, sclerotherapy seems to be preferable; for all others, it is technically easier to perform ligation. Received: 29 June 1998/Accepted: 18 September 1998     

Sevelamer Use,Vitamin K Levels,Vascular Calcifications,and Vertebral Fractures in Hemodialysis Patients: Results from the VIKI Study

Hyperphosphatemia is a risk factor for vascular calcifications (VCs), which are part of the chronic kidney disease-mineral and bone disorders (CKD-MBD). Vitamin K-dependent proteins such as matrix Gla protein (MGP) and bone Gla proteins (BGP, or osteocalcin) can inhibit VCs and regulate bone mineralization. In this analysis of the Vitamin K Italian (VIKI) study, the relationship between vitamin K status, vertebral fractures (VFs) and VCs in 387 hemodialysis (HD) patients with (N = 163; 42.1%) or without N = 224; 57.9%) sevelamer was evaluated. Levels of vitamin K vitamers K1 and K2 or menaquinones (MK; MK4–7), total and undercarboxylated (uc) forms for both BGP and MGP were determined. Although no differences in clinical characteristics were noted, lower levels of MK4 (0.45 versus 0.6 ng/mL, p = .01) and a greater MK4 deficiency was observed in sevelamer-treated patients (13.5% versus 5.4%, p = .005). Multivariate logistic regression revealed that MK4 deficiency was associated with sevelamer use (odds ratio [OR] = 2.64, 95% confidence interval [CI] 1.25–5.58, p = .011) and aortic calcification (OR = 8.04, 95% CI 1.07–60.26, p = .04). In the same logistic model, sevelamer amplified the effect of total BGP levels on the odds of VFs in patients with total BGP <150 μg/L compared with those with total BGP ≥150 μg/L (OR = 3.15, 95% CI 1.46–6.76, p = .003). In contrast, there was no such effect in those untreated (total BGP <150 μg/L versus total BGP ≥150 μg/L: OR = 1.21, 95% CI 0.66–2.23, p = .54]; p = .049 for effect modification by sevelamer). Sevelamer may interfere with MK4 levels in HD patients and interact with low BGP levels to increase bone fractures in CKD patients. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Management of Solid-pseudopapillary Neoplasms of the Pancreas: a Comparison with Standard Pancreatic Neoplasms

Background Solid-pseudopapillary neoplasms (SPNs) of the pancreas are increasingly diagnosed, but the exact surgical management in terms of extent of the resection is not well defined. Materials and Methods Patients operated on in our hospital between January 1993 and March 2005 formed the study groups. Results From 659 consecutive resections for pancreatic neoplasms, 12 female patients (1.8%) with a median age of 21 years who underwent resection for (SPN) are compared with the remaining 647 pancreatic resection patients. Jaundice (SPN 0 versus PR 73%, p < 0.001) and weight loss (SPN 0 versus PR 49%, p = 0.001) occurred significantly less often. Neoplasms were distributed equally among the pancreatic head (SPN 5 out of 12 patients versus PR 88%, p < 0.001) and corpus/tail (SPN 6 out of 12 patients versus PR 8%, p < 0.001). The operative time was significantly shorter (SPN 233 min versus PR 280 min, p = 0.012), and there were significantly fewer complications (SPN 1 of 12 patients versus PR 48%, p = 0.007). The mortality was not different (SPN 0 versus PR 1.6%, p = 1.000), and the hospital stay was significantly shorter (SPN 9 days versus PR 15 days, p = 0.012). The median size of the neoplasms was significantly larger (SPN 6.9 cm versus PR 2.5 cm). The median number of lymph nodes harvested was significantly fewer (SPN 1 versus PR 6, p = 0.001), and lymph node metastases occurred significantly less often (SPN 0 versus PR 64%, p < 0.001). The 5-year survival of SPN patients was 100% and is significantly better compared with survival of patients with pancreatic adenocarcinoma (12%, p < 0.001) and ampulla of Vater adenocarcinoma (22%, p = 0.005). Conclusions Patients with solid-pseudopapillary neoplasms of the pancreas present differently and the course of the disease is more benign. These patients can be adequately managed by pylorus-preserving pancreatoduodenectomy or spleen-preserving distal pancreatectomy with excellent early and long-term results.     

Emergency Left Colon Resection for Acute Perforation. Primary Anastomosis or Hartmann’s Procedure? A Case-matched Control Study

Background The optimal treatment remains controversial for acute left-sided colon perforation. Therefore, the effectiveness and safety of primary anastomosis versus Hartmann’s operation (HP) was compared in a case-matched control study. Methods Thirty consecutive patients with primary anastomosis and protective ileostomy (PAS) were matched to 30 HP patients, controlling for age, gender, American Society of Anesthesiologists (ASA) score, body mass index (BMI), and peritonitis severity (Hinchey). In a second analysis, PAS patients with purulent peritonitis (Hinchey 3) were matched to patients with primary anastomosis without ileostomy (PA). Results Hospital mortality was similar between HP (17%) and PAS (10%). Complication frequency and severity (requiring re-intervention or admission to the Intensive Care Unit [ICU]) were comparable for the first operation (60% versus 56% and 30% versus 32%). The stoma reversal rate was higher in PAS than in HP (96% versus 60%, p = 0.001), with significantly fewer complications (23% versus 66%, p = 0.02), and lower severity (7% versus 33%, p = 0.02). Additional analysis of PAS versus PA showed similar morbidity (52% versus 41%, p = 0.45) and complication severity (18% versus 24%, p = 0.51), whereas overall operation time and hospital stay were significantly shorter in PA (169 versus 320 min, p = 0.003, 17 versus 28 days, p < 0.001). Conclusions Primary anastomosis and protective ileostomy is a superior treatment to HP in acute left-sided colon perforation. In the absence of feculent peritonitis an ileostomy appears unnecessary. Presented at the 13th Annual Meeting of the European Surgical Association (ESA), Zurich, 2006.     

Factor V Leiden does not affect bleeding in aprotinin recipients after cardiopulmonary bypass

BACKGROUND: Carriers of the factor V Leiden mutation (FVL) are resistant to activated protein C proteolysis. Therefore, they are at increased risk of thromboembolic events. Aprotinin is an unspecific proteinase inhibitor frequently used during cardiac surgery procedures to reduce bleeding. However, aprotinin may cause thromboembolic complications after cardiopulmonary bypass (CPB). The primary endpoint of this study was the amount of blood loss after CPB in aprotinin recipients, and secondary endpoints were thromboembolic complications. METHODS: A total of 1,447 consecutive patients who underwent cardiac surgery with CPB were prospectively enrolled. All patients were screened for FVL by a fluorescence-based polymerase chain reaction method. Linear and logistic regression analyses were performed to assess associations of FVL on bleeding and thromboembolic complications. RESULTS: One hundred seven individuals (7.4%) were heterozygous FVL carriers. No difference was found between FVL carriers and noncarriers regarding age, sex, CPB, type of operation, EuroSCORE, antiplatelet treatment, and reoperation. FVL was not significantly associated with postoperative blood loss, whereas a significant influence was found for female sex (P < 0.0001), duration of CPB (P < 0.0001), reoperation (P = 0.001), and preoperative antiplatelet treatment (P < 0.002). Multiple linear regression analysis for total blood loss had an observed power of at least 99%. FVL carriers faced the same risk for postoperative transfusion (P = 0.391), reoperation (P = 0.675), myocardial infarction (P = 0.44), stroke (P = 0.701), and 30-day mortality (P = 0.4) as did noncarriers. CONCLUSIONS: These data suggest that FVL carriers do not have reduced blood loss compared with noncarriers. Furthermore, the combination of aprotinin and FVL does not enhance the risk for thromboembolic complications.     

Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation

In contrast to “classical” forms of osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain‐of‐function mutation in the IFITM5 gene, encoding the interferon‐induced transmembrane protein 5, or bone‐restricted interferon‐inducible transmembrane (IFITM)‐like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders such as hyperplastic callus and forearm interosseous membrane ossification. Little is known about the impact of the mutation on bone tissue/material level in untreated and bisphosphonate‐treated patients. Therefore, investigations of transiliac bone biopsy samples from a cohort of OI type V children (n = 15, 8.7 ± 4 years old) untreated at baseline and a subset (n = 8) after pamidronate treatment (2.6 years in average) were performed. Quantitative backscattered electron imaging (qBEI) was used to determine bone mineralization density distribution (BMDD) as well as osteocyte lacunar density. The BMDD of type V OI bone was distinctly shifted toward a higher degree of mineralization. The most frequently occurring calcium concentration (CaPeak) in cortical (Ct) and cancellous (Cn) bone was markedly increased (+11.5%, +10.4%, respectively, p < 0.0001) compared to healthy reference values. Treatment with pamidronate resulted in only a slight enhancement of mineralization. The osteocyte lacunar density derived from sectioned bone area was elevated in OI type V Ct and Cn bone (+171%, p < 0.0001; +183.3%, p < 0.01; respectively) versus controls. The high osteocyte density was associated with an overall immature primary bone structure (“mesh‐like”) as visualized by polarized light microscopy. In summary, the bone material from OI type V patients is hypermineralized, similar to other forms of OI. The elevated osteocyte lacunar density in connection with lack of regular bone lamellation points to an exuberant primary bone formation and an alteration of the bone remodeling process in OI type V. © 2017 American Society for Bone and Mineral Research.     

Levels of serotonin,sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high‐bone‐mass phenotype due to a mutation in Lrp5

Patients with an activation mutation of the Lrp5 gene exhibit high bone mass (HBM). Limited information is available regarding compartment‐specific changes in bone. The relationship between the phenotype and serum serotonin is not well documented. To evaluate bone, serotonin, and bone turnover markers (BTM) in Lrp5‐HBM patients, we studied 19 Lrp5‐HBM patients (T253I) and 19 age‐ and sex‐matched controls. DXA and HR‐pQCT were used to assess BMD and bone structure. Serum serotonin, sclerostin, dickkopf‐related protein 1 (DKK1), and BTM were evaluated. Z‐scores for the forearm, total hip, lumbar spine, forearm, and whole body were significantly increased (mean ± SD) between 4.94 ± 1.45 and 7.52 ± 1.99 in cases versus ?0.19 ± 1.19 to 0.58 ± 0.84 in controls. Tibial and radial cortical areas, thicknesses, and BMD were significantly higher in cases. In cases, BMD at the lumbar spine and forearm and cortical thickness were positively associated and trabecular area negatively associated with age (r = 0.49, 0.57, 0.74, and ?0.61, respectively, p < .05). Serotonin was lowest in cases (69.5 [29.9–110.4] ng/mL versus 119.4 [62.3–231.0] ng/mL, p < .001) and inversely associated with tibial cortical density (r = ?0.49, p < .05) and directly with osteocalcin (OC), bone‐specific alkaline phosphatase (B‐ALP), and procollagen type 1 amino‐terminal propeptide (PINP) (r = 0.52–0.65, p < .05) in controls only. OC and S‐CTX were lower and sclerostin higher in cases, whereas B‐ALP, PINP, tartrate‐resistant acid phosphatase (TRAP), and dickkopf‐related protein 1 (DKK1) were similar in cases and controls. In conclusion, increased bone mass in Lrp5‐HBM patients seems to be caused primarily by changes in trabecular and cortical bone mass and structure. The phenotype appeared to progress with age, but BTM did not suggest increased bone formation. © 2011 American Society for Bone and Mineral Research     

CT‐measured bone attenuation in patients with chronic obstructive pulmonary disease: Relation to clinical features and outcomes

Osteoporosis is highly prevalent in chronic obstructive pulmonary disease (COPD) patients and has been related to several clinical features. However, most studies have been in relatively small COPD cohorts. Therefore, the objectives of this study were to compare bone attenuation measured on low‐dose chest computed tomography (CT) between COPD subjects and smoker and nonsmoker controls, and to relate bone attenuation to clinical parameters, inflammatory biomarkers, and outcomes in a large, well‐characterized COPD cohort. We studied 1634 COPD subjects, 259 smoker controls, and 186 nonsmoker controls who participated in a large longitudinal study (ECLIPSE). We measured bone attenuation, extent of emphysema, and coronary artery calcification (Agatston score) on baseline CT scans, and clinical parameters, inflammatory biomarkers, and outcomes. Bone attenuation was lower in COPD subjects compared with smoker and nonsmoker controls (164.9 ± 49.5 Hounsfield units [HU] versus 183.8 ± 46.1 HU versus 212.1 ± 54.4 HU, p < 0.001). Bone attenuation was not significantly different between COPD subjects and smoker controls after adjustment for age, sex, and pack‐years of smoking. In the COPD subjects, bone attenuation correlated positively with forced expiratory volume in 1 second (FEV₁, r = 0.062, p = 0.014), FEV₁/forced vital capacity (FVC) ratio (r = 0.102, p < 0.001), body mass index (r = 0.243, p < 0.001), fat‐free mass index (FFMI, r = 0.265, p < 0.001), and C‐reactive protein (r = 0.104, p < 0.001), and correlated negatively with extent of emphysema (r = ?0.090, p < 0.001), Agatston score (r = ?0.177, p < 0.001), and interleukin‐8 (r = ?0.054, p = 0.035). In a multiple regression model, older age, lower FFMI and higher Agatston score were associated with lower bone attenuation. Lower bone attenuation was associated with higher exacerbation (r = ?0.057, p = 0.022) and hospitalization (r = ?0.078, p = 0.002) rates but was not associated with all‐cause mortality. In conclusion, CT‐measured bone attenuation was lower in COPD subjects compared with nonsmoker controls but not compared with smoker controls, after adjustment for age, sex, and pack‐years of smoking. In the COPD subjects, bone attenuation was associated with age, body composition, and coronary artery calcification but was not associated with all‐cause mortality.     

Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study

Objectives: Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort.

Methods: One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed.

Results: Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p?r?=??.143, p?=?.047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207?ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (<3.207?ng/ml) and with anti-PTX3 auto-antibodies (4.79 (3.39–8.28) versus 3.95 (1.78–7.0), p?=?.03; 168.84?±?153.63 versus 101.44?±?47.36, p?=?.01; 34.1% (14/41) versus 0% (0/9), p?=?.04; respectively).

Conclusion: Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.