Use of recombinant human erythropoietin to assist autologous blood donation by anemic rheumatoid arthritis patients undergoing major orthopedic surgery

BACKGROUND: In rheumatoid arthritis (RA) patients undergoing orthopedic surgery, anemia is the major factor in the use of allogeneic blood. STUDY DESIGN AND METHODS: To determine whether recombinant human erythropoietin (rHuEPO) could allow preoperative autologous blood procurement and reduce allogeneic blood exposure, 11 RA patients who were unable preoperatively to deposit blood for autologous use because of their anemia (baseline hematocrit < 34% [0.34]) and who were scheduled for primary total hip replacement or total knee replacement were treated intravenously with 300 U per kg of rHuEPO in combination with intravenous iron saccharate (100 mg), given twice weekly for 3 weeks. The transfusion treatment was compared with that in 12 control patients with comparable baseline hematologic values who underwent the same operation. RESULTS: Control patients could not preoperatively deposit any blood for autologous use, while all but one of the rHuEPO- treated patients deposited 2 or more units (mean, 2.6 +/− 0.6; range, 2- 4) (p < 0.001). The control group received more allogeneic units (2.6 +/− 1.6 vs. 0.8 +/− 0.8) (p = 0.009). Moreover, 50 percent of the rHuEPO-treated patients, as compared with 8 percent of controls, completely avoided allogeneic transfusion. CONCLUSION: Recombinant human erythropoietin is safe and effective in stimulating erythropoiesis, allowing preoperative donation of blood for autologous use, and reducing exposure to allogeneic blood for RA patients who are unable preoperatively to deposit blood because of anemia.     

Gastroesophageal pH step-up inaccurately locates proximal border of lower esophageal sphincter

Limiting the widespread use of 24-hr pH monitoring is the necessity of manometrically placing the pH probe 5 cm above the proximal lower esophageal sphincter (LES) border. Therefore, we prospectively compared LES localization by gastroesophageal pH step-up with manometry in 71 patients and 14 asymptomatic volunteers. The gastroesophageal pH step-up significantly correlated with the proximal LES border in patients (r=0.53, P<0.0001) and volunteers (r=0.91, P<0.0001). Based on previously published criteria, the pH step-up value was considered acceptably accurate if it was within ±3 cm (6 cm total span) of the manometrically determined proximal LES border. In 58% of patients and 29% of volunteers the pH step-up occurred outside this accuracy range. Esophagitis (P=0.015) and abnormal reflux parameters (P=0.002) were variables contributing to this error. Subsequent analysis found that the pH step-up overestimated the proximal LES border and occurred at the midportion of the sphincter. The pH step-up still inaccurately located the mid LES in 34% of patients. Therefore, manometry should remain the standard for accurate LES localization prior to placing the pH probe.     

Society stress and peptic ulcer perforation

To examine the relationship between society stress and peptic ulcer perforation, time-trend analysis was performed on the annual incidence of perforated peptic ulcer per 100 000 population in Hong Kong during the years 1962–85, when Hong Kong, as a developing city, went through significant socio-economic and political changes, and the trend was correlated with specially designed and validated society stress scores estimated annually during the same period. The society stress scores were derived independently by two expert panels blinded to the purpose of the study, one selecting and categorizing negative news events for Hong Kong during this period, and the other weighing the categories and scoring the impact of the news on Hong Kong. The incidence of perforation increased significantly during the years and manifested three distinct peaks, which coincided with the worst economic recession in Hong Kong, the influx of mainlander Chinese and Vietnamese boat people, and the Sino-British negotiation on the sovereignty of Hong Kong after 1997. Both linear and autoregression analysis, the latter taking into consideration point fluctuations in rates, showed that perforation rates correlated significantly with the society stress scores (r= 0.57, P < 0.002). The peak effects and the significant correlations indicate that an association exists between society stress and peptic ulcer perforation, and suggest that chronic society stress plays an important role in the aetiology of this condition, although the relatively low r value also suggests the presence of other aetiological factors.     

Alogliptin Use in Elderly People: A Pooled Analysis from Phase 2 and 3 Studies

OBJECTIVES: To compare the efficacy and safety of alogliptin, a dipeptidyl peptidase-4 (DPP-4) enzyme inhibitor, in elderly (≥65) and younger (<65) patients with type 2 diabetes mellitus.
DESIGN: Pooled analysis of six randomized, double-blind, placebo-controlled studies of alogliptin.
PARTICIPANTS: Patients aged 18 to 80 with type 2 diabetes mellitus and inadequate glycemic control.
INTERVENTIONS: Elderly (mean age 70.0; n=455) and younger (mean age 51.8; n=1,911) patients received alogliptin 12.5 mg (n=922), alogliptin 25 mg (n=910), or placebo (n=534) for 26 weeks (12 weeks in a Phase 2 study). The studies evaluated alogliptin as monotherapy and coadministered with pioglitazone, glyburide, metformin, or insulin.
MEASUREMENTS: Efficacy endpoints included change from baseline in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), weight, and lipid values. Safety variables included hypoglycemic events, adverse events, and blood pressure.
RESULTS: Least-squares mean HbA1c decreased from baseline by 0.7% and 0.8% in elderly patients receiving alogliptin 12.5 and 25 mg, respectively, and 0.5% and 0.6%, respectively, in younger patients ( P <.001 for both alogliptin doses vs placebo for both age groups P =.70 for 12.5 mg and .68 for 25 mg for differences between age groups). Results were similar for FPG. Incidence of hypoglycemia was 8.3% or less in all alogliptin groups (≤10.5% for placebo), with no apparent difference between elderly and younger patients. Changes in weight were negligible in all treatment groups in both age categories. The safety profiles of alogliptin were similar in the age and dose groups.
CONCLUSION: Alogliptin was effective and well tolerated in the elderly patients enrolled in these studies. Improvements in HbA1c were similar to those seen in younger patients, and no increase in the risk of hypoglycemia, weight gain, or other adverse events was apparent in elderly patients.     

Spectrin Nice (beta 220/216): a shortened beta-chain variant associated with an increase of the alpha I/74 fragment in a case of elliptocytosis

We describe a new spectrin variant with a truncated beta-chain. It was discovered in a 17-year-old white boy presenting with intermittent jaundice and spleen enlargement. He also displayed numerous smooth elliptocytes. On sodium dodecyl sulfate-polyacrylamide gel, the truncated beta-chain (beta'-chain) appeared as an additional band of approximately 216 kilodaltons, migrating between spectrin beta-chain and ankyrin. It represented 30% of total beta-chain. The beta'-chain reacted with an antispectrin beta-chain monoclonal antibody. It failed to become phosphorylated when ghosts were incubated in the presence of [gamma-32P] adenosine triphosphate. Whole spectrin tetramerization was defective since the amount of spectrin dimer was increased in spectrin crude extract and the association constant of the spectrin dimer self- association was decreased. Spectrin whole tetramer isolated from spectrin crude extracts contained small quantities of beta'-chain. Spectrin tryptic peptides showed an increase of the 74,000-dalton fragment at the expense of the 80,000-dalton fragment. So far, the latter abnormality has been used to characterize a number of cases of hereditary elliptocytosis or pyropoikilocytosis with no other apparent change. In the present case, we consider that the abnormality is a consequence of the beta-chain alteration. The parents seemed asymptomatic. As a result, we regard this new spectrin variant as deriving from a de novo mutation.     

Haploidentical transplantation outcomes for secondary acute myeloid leukemia: Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) study

Secondary acute myeloid leukemia (sAML) traditionally has inferior outcomes compared to de novo AML. Allogeneic hematopoietic cell transplantation (HCT) is the sole potentially curative therapy. This study analyzes the outcomes for unmanipulated haploidentical HCT (haploHCT) for sAML using the Acute Leukemia Working Party (ALWP) registry of the European Society for Blood and Marrow Transplantation (EBMT). We identified 154 patients with sAML who underwent haploHCT from 2006 to 2016. Median age at HCT was 60 years with time from diagnosis to HCT 5 months. At transplantation, 69 patients were in first CR and 85 had active disease. Fifty‐seven (38.0%) patients underwent myeloablative conditioning and 97 (62.0%) reduced intensity conditioning (RIC) conditioning. Multivariate analysis showed that there was no difference in RI, nonrelapse mortality (NRM), leukemia free survival (LFS), overall survival (OS), or GVHD‐free/relapse free survival (GRFS) for conditioning intensity, age, performance status, or graft source. Active disease was associated with higher RI and inferior LFS, OS, and GRFS compared with patients in CR at time of transplant. T‐cell depletion with anti‐thymoglobulin resulted in higher NRM and inferior LFS, OS, and GRFS compared to post‐transplant cyclophosphamide (PTCy) (HR 2.25, 2.01, 2.16, and 1.73, respectively with P values <.05). Our data shows that haploHCT is a feasible alternative for sAML when matched transplantation is unavailable.     

Risk factors for the delayed viral clearance in COVID‐19 patients

Comorbidities are important for the disease outcome of COVID‐19, however, which underlying diseases that contribute the most to aggravate the conditions of COVID‐19 patients are still unclear. Viral clearance is the most important laboratory test for defining the recovery of COVID‐19 infections. To better understand which underlying diseases that are risk factors for delaying the viral clearance, we retrospectively analyzed 161 COVID‐19 clinical cases in the Zhongnan Hospital of Wuhan University, Wuhan, China between January 5 and March 13, 2020. The demographic, clinical and laboratory data, as well as patient treatment records were collected. Univariable and multivariable analysis were performed to explore the association between delayed viral clearance and other factors by using logistic regression. Survival analyses by Kaplan‐Meier and Cox regression modeling were employed to identify factors negatively influencing the viral clearance negatively. We found that hypertension and intravenous immunoglobulin adversely affected the time of viral RNA shedding. Hypertension was the most important risk factor to delay the SARS‐CoV‐2 virus clearance, however, the use of Angiotensin‐Converting Enzyme Inhibitors(ACEI)/Angiotensin Receptor Blockers(ARB) did not shorten the time for virus clearance in these hypertensive patients’ virus clearance. We conclude that patients having hypertension and intravenous immunoglobulin may delay the viral clearance in COVID‐19 patients.     

How Does Aging Affect Presentation and Management of Biliary Stones?

Common bile duct (CBD) stones are common in elderly adults, but the effect of aging on the presentation of CBD stones remains to be evaluated. Recent studies have demonstrated that the clinical presentation of CBD stones may vary with age. Younger adults may present with classical biliary colic symptoms, whereas elderly adults may have no unapparent clinical features. Younger adults with CBD stones were significantly more likely to have abnormal liver function tests than those without. The sensitivity and accuracy of transabdominal ultrasound scans in screening for CBD stones increases with age. Antibiotic agents should be promptly administered to individuals with CBD stones complicated by cholangitis, but the effects of pharmacotherapy on renal function should be considered in elderly adults. Endoscopic retrograde cholangiopancreatography (ERCP) is considered to be first‐line treatment for CBD stones, and endoscopic biliary sphincterotomy (EST) or endoscopic papillary balloon dilation (EPBD) along with ERCP is an adequate biliary drainage method in individuals with CBD stones. EPBD has a lower bleeding risk but higher post‐ERCP risk of pancreatitis than EST. Longer‐duration (>1 minute) EPBD may be preferred over EST because it is associated with a comparable risk of pancreatitis but a lower rate of overall complications, although recurrent cholangitis or unfavorable outcomes will increase during CBD dilation or in the presence of residual CBD stones.     

Assessment of baroreflex sensitivity in patients with preserved and impaired left ventricular function by means of the Valsalva manoeuvre and the phenylephrine test

The purpose of the present study was to assess the agreement between measurements of baroreflex sensitivity (BRS) obtained by the Valsalva manoeuvre and by the phenylephrine test in patients with previous myocardial infarction and different degrees of left ventricular dysfunction. Patients with a previous myocardial infarction were enrolled consecutively into two groups according to their left ventricular ejection fraction (LVEF): 40% (n=52). All patients underwent BRS assessment by the phenylephrine technique (Phe-BRS) and by the Valsalva manoeuvre, with the latter using both the overshoot part of phase IV (Ov-VM-BRS) and the whole of phase IV (IV-VM-BRS). The linear association between methods was assessed by correlation analysis and the agreement was evaluated by computing the bias and the limits of agreement. IV-VM-BRS and Ov-VM-BRS could not be computed in 26% and 39% of patients respectively. For both indices a much higher percentage of non-computable Valsalva manoeuvre slopes was found in the group of patients with LVEF 40% the results were: r=0.91 (P<0.001), bias=0.1 ms/mmHg (P=0.84) and limits of agreement from -4.8 to 5 ms/mmHg. When comparing Phe-BRS and IV-VM-BRS, we found r=0.67 (P=0.001), bias=-1.5 ms/mmHg (P=0.06) and limits of agreement from -8.8 to 5.7 ms/mmHg in the group of patients with LVEF 40%. Dichotomizing Ov-VM-BRS, the best cut-off value to identify patients with a Phe-BRS of <3 ms/mmHg was found to be 7 ms/mmHg, giving 100% sensitivity and 69% specificity. In conclusion, estimation of BRS by the Valsalva manoeuvre in post-myocardial infarction patients is limited by a large number of non-measurable results. When computable, measurements are well correlated with those obtained by Phe-BRS, but, because of large limits of agreement, the two methods cannot be used interchangeably. If used as a screening test for risk stratification, the Valsalva manoeuvre could reduce by about one-third the need for phenylephrine injection.     

Collection of peripheral blood hematopoietic progenitors (PBHP) from patients with severe aplastic anemia (SAA) after prolonged administration of granulocyte colony-stimulating factor

The aim of this study was to test whether prolonged administration of granulocyte colony-stimulating factor (G-CSF) would allow the collection by leukapheresis of PBHP in patients with SAA. For this purpose, nine SAA patients, 7 to 46 years old, six of whom were enrolled at diagnosis of their disease and three after previous immunosuppression had failed, were treated with antilymphocyte globulin (ALG) (day 1 to 5), cyclosporin A (5 mg/kg/d orally) (day 6 to 90) and G-CSF 5 micrograms/kg/d (day 6 to 90). A total of 40 leukaphereses were performed, (range 2 to 7 per patient), between days +10 and +168 from G- CSF treatment. White blood cell count at the time of harvest ranged from 1.2 to 18.1 x 10(9)/L. Results can be summarized as follows: the median number of cells collected per patient was 5.0 x 10(8)/kg (range 2.6 to 18.7), the median number of CD34+ cells was 1.8 x 10(6)/kg (range 0.27 to 3.8) and the median number of colony-forming units granulocyte-macrophage (CFU-GM) was 3.9 x 10(4)/kg (range 0 to 39). Twenty leukaphereses performed between days +33 and +77 of G-CSF treatment grew granulocyte macrophages and erythroid colonies in vitro. No colony growth was obtained from 20 leukaphereses performed before day +33 or after day +80. In six patients the total number of CFU-GM recovered were in the range described for autologous peripheral blood stem cell grafts. (2.6 to 39 x 10(4)/kg). In conclusion, this study suggests that circulating hematopoietic progenitors can be recovered after ALG priming and after at least 1 month of G-CSF treatment in a proportion of patients with SAA. Whether these cells will be suitable for autologous transplantation remains to be determined.