A Modified Post-Transplant Cyclophosphamide Regimen,for Unmanipulated Haploidentical Marrow Transplantation,in Acute Myeloid Leukemia: A Multicenter Study

We report a modified post-transplant cyclophosphamide (PT-CY) regimen, for unmanipulated haploidentical marrow transplants, in 150 patients with acute myeloid leukemia (AML). All patients received a myeloablative regimen, cyclosporine A (CsA) on day 0, mycophenolate on day +1, and PT-CY 50?mg/kg on days +3 and +5. The median age was 51 (range, 17–74) years, 51 (34%) patients had active disease at transplant, and the median follow-up of surviving patients 903 (range, 150-1955) days. The cumulative incidence (CI) of engraftment, acute graft-versus-host disease (GVHD) grade II to IV, and moderate/severe chronic GVHD was 92%, 17%, and 15%, respectively. The 4-year CI of transplant-related mortality (TRM) and relapse was 20% and 24%, respectively. Four-year survival for remission patients was 72% (74% versus 67% for <60 or ≥60 years of age) and 26% for advanced patients (17% versus 41% for <60 or ≥60 years of age). In a multivariate analysis, active disease at transplant was the only negative predictor of survival, TRM and relapse. The original PT-CY regimen can be modified with CsA on day 0, still providing protection against GVHD, low toxicity, and encouraging low relapse incidence in AML patients, also over 60 years of age.     

Pronase independent flow cytometry crossmatching of rituximab treated patients

ABO-incompatible (ABOi) kidney transplantation has become an established strategy to increase the number of available living donors. At our center, the conditioning protocol for ABOi patients is based on anti-A/B antibody removal and depletion of B cells with the anti-CD20 mAb rituximab (Mabthera®). It is known that even low amounts of remaining rituximab in serum of patients results in false positive B cell cross match results, masking detection of potentially harmful donor human leukocyte antigen (HLA) specific antibodies. Treatment of donor cells with high concentrations (>1?mg/mL) of pronase is currently standard procedure for elimination of rituximab (RIT) interference. It is, however, troublesome that recent reports indicate that pronase treatment per se can induce incorrect flow cytometry cross match (FCXM) results. The aim of this study was to evaluate an alternative pronase-free FCXM for crossmatching of patients treated with rituximab.FCXM with an anti-RIT monoclonal antibody (mAb) pre-blocking step were evaluated on normal human sera (NHS) and patient sera supplemented with RIT. NHS supplemented with RIT or patient sera, without donor specific antibodies (DSA), resulted in high B cell median channel shift (>200 IgG) above background. This shift was eliminated by a serum pre-blocking step with 2-fold excess of anti-RIT (clone MB2A4). Blocking with anti-RIT did not influence the T cells crossmatch results. We present data supporting proof-of-concept that blocking with anti-RIT antibody prior to XM can enable reliable detection of anti-HLA class I and II donor specific antibodies without use of pronase treated donor cells.     

Risk Factors for Severe Acute Graft-versus-Host Disease in Donor Graft Composition

Acute graft-versus-host disease (aGVHD) is 1 of the main major complications of post–hematopoietic stem cell transplantation (HSCT). Identifying patients at risk of severe aGVHD may lead to earlier intervention and treatment, resulting in increased survival and a better quality of life. We aimed to identify biomarkers in donor grafts and patient plasma around the time of transplantation that might be predictive of aGVHD development. We build on our previously published methods by using multiplex assays and multicolor flow cytometry. We identified 5 easily assessable cellular markers in donor grafts that combined could potentially be used to calculate risk for severe aGVHD development. Most noteworthy are the T cell subsets expressing IL-7 receptor-α (CD127) and PD-1. Additionally, we identified a potential role for elevated tumor necrosis factor-α levels in both graft and patient before HSCT in development of aGVHD.     

Comparison between the effects on hemodynamic responses of central and peripheral infusions of hypertonic NaCl during hemorrhage in conscious and isoflurane-anesthetized sheep

The i.v. infusion of hypertonic NaCl solutions, as in small volume hypertonic NaCl resuscitation, improves cardiovascular function in hypovolemic shock. The mechanism(s) of action of this treatment is(are) not fully elucidated. In this study, we investigate the possible importance of fully functional neurocardiovascular regulation for the effect of intracerebroventricular (i.c.v.) and i.v. administration of hypertonic NaCl on the hemodynamic responses to hemorrhage. Six groups (each n = 6) of adult ewes were subjected to hypotensive hemorrhage during treatment with i.c.v. infusion (20 microL/min) of either artificial cerebrospinal fluid (controls) or 0.5 mol/L NaCl, or i.v. infusion of 1.2 mol/L NaCl (4 mL/kg) when conscious, respectively anesthetized with isoflurane. Thirty minutes into infusion, treatment blood was withdrawn at 0.7 mL/kg per minute from a jugular vein until the mean arterial pressure dropped to a value just below 50 mmHg. In conscious animals, the amount of blood loss needed to lower the mean arterial pressure to less than 50 mmHg was increased by the i.c.v. and i.v. infusions of hypertonic NaCl (24.0 +/- 4.6 and 22.4 +/- 3.3 mL/kg, respectively), compared with controls receiving i.c.v. infusion of artificial cerebrospinal fluid (14.2 +/- 1.4 mL/kg). Isoflurane anesthesia, as such, severely compromised the cardiovascular compensatory mechanisms activated by hemorrhage and reduced the blood loss necessary to cause hypotension (10.2 +/- 2.5 mL/kg). Furthermore, anesthesia totally abolished the effect of i.c.v. hypertonic NaCl (10.4 +/- 2.2 mL/kg) and blunted the response to i.v. hypertonic NaCl (15.9 +/- 2.1 mL/kg) seen in conscious animals. The results show that an intact autonomic cardiovascular control is crucial for the effect of i.c.v. hypertonic saline and indicate that i.v. hypertonic saline exerts some of its action through the central nervous system.     

Workplace NO and NO2 during combined treatment of infants with nasal CPAP and NO

Objective To determine the workplace concentrations of NO and NO₂ in and around a paediatric incubator during inhaled NO (iNO) treatment and during an accidental emptying of NO cylinders into room air.Design We simulated iNO–nasal CPAP treatment in order to assess the impact on the occupational environment. Furthermore, two full NO cylinders for therapy, 1,000 ppm, 20 litres, 150 bar and 400 ppm, 10 litres, 150 bar, were emptied as rapidly as possible into an intensive care unit (ICU) room.Setting University hospital ICU.Measurements and results To correctly gauge the contribution from iNO–CPAP we constructed a system measuring breathing zone and room ventilation inlet-outlet values during a 10-ppm iNO treatment of a simulated infant. Maximal breathing zone values were 17.9 ± 7.0 (mean ± 95% CI) ppb for NO and 25.2 ± 4.8 ppb for NO_2. If room inlet values were subtracted, the contributions to breathing zone values emanating from iNO–CPAP were 14.8 ± 4.6 ppb for NO and 14.6 ± 4.6 ppb for NO₂. At the ventilation outlet the maximal contributions were 4.2 ± 2.9 ppb NO and 9.6 ± 4.3 ppb NO₂. During rapid total release of a gas cylinder in the ICU room, simulating an accident, we found transient NO levels comparable to the high therapeutic dosing range, but only low NO₂ levels.Conclusions Neither 8-h time-weighted average (TWA) nor 15 min short-term exposure limits (STEL) were exceeded during normal operation or during a simulated accident. The contribution of nitrogen oxides from treatment to workplace air were minor compared to those from ambient air.     

A new application of pre-normalized principal component analysis for improvement of image quality and clinical diagnosis in human brain PET studies--clinical brain studies using [11C]-GR205171, [11C]-L-deuterium-deprenyl, [11C]-5-Hydroxy-L-Tryptophan, [11C]-L-DOPA and Pittsburgh Compound-B

Principal component analysis (PCA) is one of the most applied multivariate image analysis tool on dynamic Positron Emission Tomography (PET). Independent of used reconstruction methodologies, PET images contain correlation in-between pixels, correlations in-between frame and errors caused by the reconstruction algorithm including different corrections, which can affect the performance of the PCA. In this study, we have investigated a new approach of application of PCA on pre-normalized, dynamic human PET images. A range of different tracers have been used for this purpose to explore the performance of the new method as a way to improve detection and visualization of significant changes in tracer kinetics and to enhance the discrimination between pathological and healthy regions in the brain. We compare the new results with the results obtained using other methods. Images generated using the new approach contain more detailed anatomical information with higher quality, precision and visualization, compared with images generated using other methods.     

Salvage of failed trochanteric and subtrochanteric fractures using a distally fixed, modular, uncemented hip revision stem: 30 patients followed for a mean of 4 years

Background and purpose

Treatment options for failed internal fixation of hip fractures include prosthetic replacement. We evaluated survival, complications, and radiographic outcome in 30 patients who were operated with a specific modular, uncemented hip reconstruction prosthesis as a salvage procedure after failed treatment of trochanteric and subtrochanteric fractures.

Patients and methods

We used data from the Swedish Hip Arthroplasty Register and journal files to analyze complications and survival. Initially, a high proportion of trochanteric fractures (7/10) were classified as unstable and 12 of 20 subtrochanteric fractures had an extension through the greater trochanter. Modes of failure after primary internal fixation were cutout (n = 12), migration of the femoral neck screw (n = 9), and other (n = 9).

Results

Mean age at the index operation with the modular prosthesis was 77 (52–93) years and the mean follow-up was 4 (1–9) years. Union of the remaining fracture fragments was observed in 26 hips, restoration of proximal bone defects in 16 hips, and bone ingrowth of the stem in 25 hips. Subsidence was evident in 4 cases. 1 patient was revised by component exchange because of recurrent dislocation, and another 6 patients were reoperated: 5 because of deep infections and 1 because of periprosthetic fracture. The cumulative 3-year survival for revision was 96% (95% CI: 89–100) and for any reoperation it was 83% (68–93).

Interpretation

The modular stem allowed fixation distal to the fracture system. Radiographic outcome was good. The rate of complications, however—especially infections—was high. We believe that preoperative laboratory screening for low-grade infection and synovial cultures could contribute to better treatment in some of these patients.The failure rate after surgery for extracapsular hip fractures is low. Occasionally, cutout and migration of the femoral neck screw occur regardless of whether a sliding hip screw or an intramedullary nail is used (Stern 2007). Implant failure after open or closed reduction and internal fixation is mostly seen in patients with unstable fracture patterns, poor bone quality, or poor positioning of the internal fixation device (Haidukewych et al. 2001).It is often difficult to find straightforward solutions. For younger patients, a second attempt at osteosynthesis with or without bone grafting may be favored. For elderly patients, prosthetic replacement is attractive, allowing immediate ambulation without fear of further fracture complications (Stern 2007).A salvage procedure converting failed internal fixation to a cemented primary total hip arthroplasty (THA) is challenging due to pre-existing and acquired osteoporosis, deformation of the trochanteric region, and difficulties in obtaining cement pressurization because of cortical screw holes (Zhang et al. 2004). Thus, an uncemented hip revision arthroplasty in these cases would appear attractive. These implants are designed to bypass regions of proximally deficient bone and to obtain stability and fixation in the distal femoral bone where there is good bone stock.There have been few reports on salvage THA with modular revision implants, and the numbers of patients have been limited (n = 10–23) (Laffosse et al. 2007, Talmo and Bono 2008, D’Arrigo et al. 2010, Abouelela 2011, Thakur et al. 2011). We reviewed a series of patients who had been operated with a specific modular, uncemented hip revision arthroplasty for failure of internal fixation of trochanteric and subtrochanteric fractures.     

High clinical utility of computed tomography compared to radiography in elderly patients with occult hip fracture after low-energy trauma

To evaluate the clinical utility of computed tomography (CT) compared to radiography in evaluating suspect or missed hip fractures in elderly after low-energy trauma. One hundred ninety-three hip CT examinations performed in two trauma centers during 3 years of evaluation of clinically suspect or occult hip fracture within 24 h of negative or suspect radiography were retrospectively reviewed. Consensus CT diagnosis by three observers was compared to clinical outcome and in some cases also further imaging. All patients were elderly and had sustained a low-energy trauma. Eighty-four examinations revealed no fracture. Follow-up was uneventful but for two patients who had been operated. Thirty-nine of 41 cervical hip fractures were surgically or otherwise confirmed, two cases were not operated due to week-old trauma and moderate symptoms. Twenty-nine of 68 trochanteric fractures or avulsions were confirmed surgically. Computed tomography has a high clinical utility as it can detect nearly all clinically suspect but radiographically negative cervical hip fractures as well as most trochanteric fractures and avulsions. A negative CT is near-perfect in ruling out a hip fracture requiring surgery.     

Quality of Care for Maternal and Newborn Health in Health Facilities in Nepal

Introduction

Nepal has pledged to substantially reduce maternal and newborn death by 2030. Improving quality of intrapartum health services will be vital to reduce these deaths. This paper examines quality of delivery and newborn services in health facilities of Nepal.

Methods

Data were sourced from the Nepal Health Facility Survey 2015, which covered a national representative sample of health facilities. The datasets were analysed to assess service readiness, availability and quality of delivery and newborn care in a sample of 992 health facilities.

Results

Of the 992 facilities in the sample, 623 provided delivery and newborn care services. Of the 623 facilities offering delivery and newborn care services, 13.3% offered comprehensive emergency obstetric care (CEmONC), 19.6% provided basic emergency obstetric care (BEmONC) and 53.9% provided basic delivery and newborn service. The availability of essential equipment for delivery and newborn care was more than 80% in health facilities. Except for the coverage of vitamin K injection, the coverage of immediate newborn care was more than 85% in all health facilities. The coverage of use of chlorhexidine ointment to all newborns was more than 70% in government hospitals and primary health care centers (PHCCs) and only 32.3% in private hospitals.

Conclusions

These findings show gaps in equipment and drugs, especially in PHCCs and private health facilities. Improving readiness and availability of equipment and drugs in PHCCs and private health facility will help improve the quality of care to further reduce maternal and newborn mortality in Nepal.