Venous thromboembolism prevention through the use of novel Factor Xa inhibitors.

The risk of a venous thromboembolic event is not limited to the pre-hospital, hospital, or immediate post-hospital period. Because of challenges with data collection, the risk of venous thromboembolism (VTE) up to 3 months post-hospitalization for patients with acute and serious medical problems in the setting of chronic disease and/or risk factors for VTE is probably under reported. The growing acceptance and indications of direct oral anticoagulants (DOACs) now includes an indication for VTE prevention for one of the Factor Xa agents. In this paper, the authors explore the issue of VTE in the extended post-hospital period and strategies to provide protection from these morbid and potentially mortal events with oral anticoagulants.

Pulmonary Nocardiosis: Unusual Presentation in Intensive Care Unit.

Pulmonary nocardiosis is a rare disease, which mainly affects immunocompromised hosts such as uncontrolled diabetics; HIV patients; and patients on immunosuppressive therapies such as anticancer drugs, systemic steroids, and transplant recipients. The diagnosis is often missed and delayed, resulting in inappropriate treatment and thus higher mortality. We are reporting a case of pulmonary nocardiosis with acute presentation in an immune-competent host, who presented with community-acquired pneumonia to the Intensive Care Unit. Clinical expertise with multiple high-end and interventional investigations timely confirmed the case as pulmonary nocardiosis. Conservative management with medications led to her complete recovery.

Successful second hematopoietic cell transplantation in severe congenital neutropenia.

Allogeneic HCT is curative for SCN; however, a standard conditioning regimen or intensity has not been established. We describe a patient with SCN associated with c.1A>G (M1V) mutation in ELANE gene resulting in refractoriness to G-CSF, who received reduced-intensity HCT and developed secondary graft failure requiring a second myeloablative HCT. This case suggests that M1V mutation confers a poor G-CSF response and HCT using the best available donor is beneficial.

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplant Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents: Part 2-Focus on Ascites, Fluid and Electrolytes, Renal, and Transfusion Issues

Even though hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic cell transplantation (HCT), there is paucity of research on the management of associated multiorgan dysfunction. To help provide standardized care for the management of these patients, the HCT Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators and the Supportive Care Committee of the Pediatric Blood and Marrow Transplant Consortium, collaborated to develop evidence-based consensus guidelines. After conducting an extensive literature search, in part 2 of this series we discuss the management of fluids and electrolytes, renal dysfunction; ascites, pleural effusion, and transfusion and coagulopathy issues in patients with VOD. We consider the available evidence using the GRADE criteria.

Entero-enteric fistula from the stump of an end-to-side ileocolic anastomosis mimicking cancer recurrence.

Enteric fistulae are a complex and technically frustrating complication of any bowel surgery. The constellation of associated non-specific symptoms often leads to extensive investigation and, in this case, suspicion of disease recurrence. A 71-year-old gentleman with a history of previous colorectal cancer presented with chronic diarrhoea, weight loss and left lower quadrant pain. Elective exploratory laparoscopy was performed to investigate possible disease recurrence due to elevated carcinoembryonic antigen levels and a positron emission tomography positive area within the mesentery. A jejunal-ileal fistula was found at laparotomy where the blind ileal stump of the end-to-side ileocolic anastomosis had fistulated into the jejunum. Resection of the affected jejunum was performed with end-to-end jejuno-jejunal re-anastomosis and stapling of the ileal stump. Specimen histology was negative for recurrence. Intestinal fistulae represent a diagnostic challenge. This is the first case report describing an enteric fistula mimicking cancer recurrence.

Outcome of children who experience disease relapse following allogeneic hematopoietic SCT for hematologic malignancies.

Relapse after allogeneic hematopoietic SCT (HSCT) carries a poor prognosis and is a common cause of death. Outcomes of children who relapse post HSCT are not well known. In this retrospective multicenter study we included 532 patients who underwent allogeneic HSCT and examined the outcomes of 160 patients (30%) who relapsed. Treatment options after relapse included (i) palliative therapy with non-curative intent (n=43), (ii) salvage chemotherapy (without a second HSCT, n=55) or (iii) salvage chemotherapy followed by a second HSCT (n=62). Sixty two patients underwent a second HSCT. The 1-year disease-free survival (DFS) for those given palliative therapy, chemotherapy alone and who underwent a second transplant was <1%, 9% and 50% (P=<0.0001), respectively. The DFS at 1 and 2 year was 50% and 35%, respectively, among the patients who received a second transplant versus 9% and 2% in those who did not (P=<0.0001). In multivariable analysis longer time to relapse (P=0.04) and undergoing a second HSCT (P<0.001) were associated with improved outcome. Withdrawal of immunosuppressive therapy, followed by curative intent chemotherapy should be offered to all patients who relapse after an allogeneic HSCT. A second HSCT should be considered, especially in patients who respond to salvage chemotherapy.

Twice daily i.v. bolus tacrolimus infusion for GVHD prophylaxis in children undergoing stem cell transplantation.

Tacrolimus is routinely administered for GVHD prophylaxis as a 24-h continuous infusion that requires a dedicated i.v. line and thus becomes logistically difficult to administer, especially in young pediatric patients. We investigated the safety and efficacy of twice daily bolus infusions of i.v. tacrolimus in 33 children undergoing hematopoietic stem cell transplantation (HSCT) at our institution. Tacrolimus was started at an initial dose of 0.015 mg/kg i.v. bolus administered as a 2-h infusion and then given at every 12 h to maintain a trough drug level between 5-15 ng/mL. Patients also received short-course MTX (66%) or mycophenolate mofetil (34%) in combination with tacrolimus. No acute infusional toxicities were observed with bolus infusions of i.v. tacrolimus. Nephrotoxicity occurred in 14/33 (42%) patients and 48% developed hypertension (HT). Almost all (94%) patients required magnesium supplements to maintain magnesium (Mg) levels 1.5 mg/dL. In all, 3 (9%) patients developed severe sinusoidal obstruction syndrome (SOS). One patient developed posterior reversible leuko-encephalopathy syndrome (PRES) and one additional patient had tremors. The prevelance of these side-effects was similar to those reported for continuous i.v. administration. In all, 28% of the evaluable patients developed acute GVHDgrade II, though the incidence of severe (grade III-IV) GVHD was only 7%. These results suggest that intermittent bolus i.v. tacrolimus administration is a safe and effective method of GVHD prophylaxis in children.

A 12-year review of Staphylococcus aureus bloodstream infections in haemodialysis patients: more work to be done.

Staphylococcus aureus bloodstream infections (BSI) are a significant cause of morbidity and mortality in haemodialysis patients. This study describes a 12-year retrospective review of S. aureus BSI in a large haemodialysis centre in a tertiary referral hospital. The overall rate of S. aureus BSI was 17.9 per 100 patient-years (range 9.7-36.8). The rate of meticillin-resistant S. aureus (MRSA) BSI was 5.6 per 100 patient-years (range 0.9-13.8). Infective complications occurred in 11% of episodes, the most common being infective endocarditis (7.6%). Ten percent of patients died within 30 days of S. aureus being isolated from blood. Most cases of S. aureus BSI (83%) were related to vascular catheters. The provision of lower-risk vascular access, such as arteriovenous fistulae, and reduced use of intravascular catheters should be priorities in all haemodialysis units. Where alternative vascular access cannot be established, interventions to reduce the risk of catheter-related infections should be implemented to reduce morbidity and mortality in this vulnerable patient group.

First Report of Alternaria alternata Causing Leaf Spot on Rumex dentatus in Pakistan.

Rumex dentatus L., commonly known as toothed dock, is an annual and biennial weed in the Polygonaceae. It is reported to be native to southern and eastern Asia and is now established in North America (southern Arizona and Sonora and Baja California) and Europe (Russia, Bulgaria, Greece, and Romania) (1,3). In Pakistan, R. dentatus is one of the most common and problematic weeds in wheat fields (2). In surveys of wheat-growing areas in Punjab Province conducted from 1999 to 2002, leaf spots were found to be very common on R. dentatus. The disease led to 10 to 70% mortality of R. dentatus in various fields in Lahore and Kasur districts. Symptoms initially were small, light brown, circular spots with most becoming irregular, dark brown lesions, while a few remained circular with concentric rings. On severely diseased leaves, several spots coalesced to form large necrotic areas. Leaf spots varied from 2 to 24 mm in diameter. The disease first appeared in mid-February, was widespread from the end of February through March when temperatures ranged from 25 to 30°C, and ended in April. Diseased leaves were cut into small fragments, surface disinfested with 1% sodium hypochlorite, rinsed thrice with sterile water, and cultured on potato dextrose agar in a growth incubator at 25 ± 1°C. The isolated fungal species was transferred to agar slants to maintain pure cultures. The fungal colony surface was grayish white, and then darkened, becoming greenish black or olive-brown with a light border. The fungus produced abundant, branched, septate, brownish hyphae with simple, olive-brown, septate conidiophores that were variable in length. Conidia were terminal, solitary, or in short chains, mostly ovoid with a short conical or cylindrical apical beaks not exceeding one-third of the conidial length, and smooth walled or vemuculose. On the basis of morphological characteristics, the fungus was identified as Alternaria alternata by the Fungal Culture Bank of Pakistan (FCBP). A specimen of the fungal culture was deposited in FCBP. For the pathogenicity test, R. dentatus plants grown outdoors from seed to three- to four-leaf stages were transplanted into 12-cm-diameter plastic pots, two plants per pot. Plants were sprayed with a suspension of the putative pathogen containing 1 × 107 conidia per ml. Control plants were sprayed with sterile water. Each treatment was replicated three times. Plants were covered for 24 h with plastic bags to maintain 100% relative humidity. The bags were removed and plants returned outdoors. All of the inoculated plants showed the same symptoms as observed on diseased plants in the field. The lesions first appeared after 7 days. The pathogen was consistently reisolated from the lesions. The pathogenicity tests were repeated three times. Given the effects of A. alternaria on R. dentatus observed in the field, there is potential for using the fungus as a biological control of the weed. References: (1) C. L. Hitchcock et al. Vascular Plants of the Pacific Northwest. Part 2, University of Washington Press, Seattle. 1964. (2) I. Siddiqui and R. Bajwa. Pak. J. Biol. Sci. 4:492, 2001. (3). USDA. Rumex dentatus L. United States Department of Agriculture Agricultural Research Service, Germplasm Resources Information Network. Online publication, 2008.

Routine electrodiagnosis and a multiparameter technique in lumbosacral radiculopathies.

OBJECTIVE: This study compares Routine nerve conductions studies (NCS)/needle electromyography (nEMG) with a multiparameter recording method (NC-stat; NeuroMetrix Inc., Waltham, MA, USA) in patients with lumbosacral radiculopathies (LSR). METHODS: Charts from 34 consecutive patients with a clinical history and/or examination consistent with an LSR were retrospectively reviewed. All underwent both Routine NCS/nEMG studies and NC-stat EDX. NC-stat testing included peroneal and posterior tibial nerve distal motor latencies and amplitudes and F-wave analysis. Twenty-eight patients had magnetic resonance imaging of the lumbosacral spine, and two had post-myelogram computerized tomography scan. RESULTS: In the 24 patients with abnormal routine NCS/nEMG, NC-stat EDX was abnormal in 22. Raw agreement values between specific abnormal Routine and NC-stat EDX parameters ranged from 065 to 0.76. NC-stat amplitude and F-wave data provide reasonable electrodiagnostic 'rule in, rule out' information for LSR. Routine and NC-stat EDX had comparable positive and negative likelihood ratios with radiographic findings based on blinded neuroradiological evaluation. This included good 'stand alone' values for NC-stat F-wave and compound muscle action potential (CMAP) amplitude abnormalities in patients with spinal stenosis. CONCLUSIONS: This report supports the value of multiparameter clinical neurophysiological evaluations in patients with LSR including CMAPs and F-waves.

The Heartfile Lodhran CVD prevention project--end of project evaluation

Mainstream preventive interventions often fail to reach poor populations with a high risk of cardiovascular diseases (CVDs) in Pakistan. A community-based CVD primary prevention project aimed at developing approaches to reduce risk factors in such populations was established by Heartfile in collaboration with the National Rural Support Program in the district of Lodhran. The project implemented a range of activities integrated with existing social and health service mechanisms during a three year intervention period 2000/01-03/04. These were targeted in 4 key settings: community health education, mass media interventions, training of health professionals and health education through Lady Health Workers. The project received support from the Department for International Development, U.K. At the community level, a pre-test-post-test quasi-experimental design was used for examining project outcomes related to the community component of the intervention. Pre and post-intervention (training) evaluations were conducted involving all health care providers in randomly selected workshops in order to determine baseline levels of knowledge and the impact of training on knowledge level. In order to assess practices of physician and non-physician health care providers patient interviews, with control comparisons were conducted at each health care facility. Significant positive changes were observed in knowledge levels at a community level in the district of intervention compared with baseline knowledge levels particularly in relation to a heart healthy diet, beneficial level of physical activity, the causes of high blood pressure and heart attack and the effects of high blood pressure and active and passive smoking on health. Significant changes in behaviors at a practice level were not shown in the district of intervention. However the project played a critical role in spurring national action for the prevention and control of non-communicable diseases and introducing sustainable public health interventions for poor communities in Pakistan. (AU)

Demographic study of leukaemia presenting within the first 3 months of life in the Northern Health Region of England.

AIMS: To determine the incidence and outcome of congenital leukaemia. METHODS: Retrospective population based study of putative leukaemia arising during the first 3 months of life over an 18 year period within the Northern Health Region of England. RESULTS: Nine infants with putative leukaemia were identified. Five had acute leukaemia and four had transient myeloproliferative disorder (TMD). Trisomy 21, either as Down's syndrome or perhaps restricted to proliferating marrow cells, was present in all four infants with TMD. The incidence of congenital acute leukaemia was 8.6/10(6) live births/year, but would be less than half this value if only patients presenting within 4 weeks of birth were counted. Remission was induced in three of the five patients with acute leukaemia. One patient, who presented at birth, remains well five years after diagnosis. All four patients with TMD survive. CONCLUSIONS: Congenital leukaemia is very rare but is not inevitably fatal. Finding trisomy 21 in spontaneously dividing blood or bone marrow cells of an infant with putative acute leukaemia, particularly within 3 months of birth, should encourage a cautious clinical approach and suggests that the diagnosis might be TMD.

Effects of growth hormone on leucine absorption, intestinal morphology, and ultrastructure of the goldish intestine.

The mechanisms whereby exogenous growth hormone modulates intestinal structure and function in fish were investigated. Goldfish (Carassius auratus) were fed commercial flake diet sprayed with recombinant carp growth hormone (cGH) daily for 1 month. Control animals received food sprayed with the vehicle. After 1 month of daily feedings, body mass and length were determined, and animals were sacrificed to study intestinal characteristics. Sections of foregut were removed after determination of total gut length for measurement of leucine uptake, histology, and epithelial ultrastructure. Oral administration of cGH for 1 month resulted in a 40% increase in body mass and an 8% increase in body length above controls. Gut length was 43% greater and the gut length to body length ratio was 32% greater as a result of the cGH treatment. Feeding with cGH also resulted in a significant increase in leucine uptake and increased gut mucosal thickness. Analysis of transmission electron micrographs revealed significant increases in the microvillous height and density and epithelial surface area. The findings indicate that growth hormone added to feed may increase growth in fish, in part by significantly increasing gut length, mucosal thickness, and epithelial brush border surface area, leading to enhanced epithelial absorption.

Recombinant tissue plasminogen activator for treatment of hepatic veno-occlusive disease following bone marrow transplantation in children: effectiveness and a scoring system for initiating treatment.

Hepatic veno-occlusive disease (HVOD) following bone marrow transplantation is potentially fatal. Criteria for diagnosis and starting treatment are mainly based on adult studies. Recombinant tissue plasminogen activator (rtPA) has been used with variable success. rtPA and heparin were given to 12 children (nine with immunodeficiency, two malignancy, one thalassaemia) with moderate to severe HVOD. Of the 12, 10 responded with a fall in bilirubin concentration; eight survived with complete resolution of HVOD. Four of the five patients with associated multiorgan failure (MOF) died despite rtPA treatment. One child suffered significant, and one minor, bleeding during rtPA treatment. A scoring system for quantifying the severity of HVOD in children is proposed, incorporating the criteria used to diagnose HVOD, risk factors for its development and also parameters reflective of the patient's general condition. This will facilitate early diagnosis and management of those cases which, if not treated promptly, are likely to deteriorate with an adverse outcome. Our experience suggests rtPA and heparin are an effective treatment for HVOD in children, with relatively little toxicity provided therapy is started before MOF develops.

Chemotherapy and marrow transplantation for congenital leukaemia.

The optimum approach to congenital leukaemia is unclear. Results of treatment are generally discouraging and palliation is offered to many. The successful treatment of an infant with congenital leukaemia is reported.

Adenovirus-mediated delivery of rhodopsin-promoted bcl-2 results in a delay in photoreceptor cell death in the rd/rd mouse.

Gene transfer to retinal cells may provide a means to retard photoreceptor cell death and thus prevent blindness in diseases such as retinitis pigmentosa. We tested the possibility of interfering with apoptotic photoreceptor cell death in the rd mouse through subretinal delivery of a recombinant replication-defective adenovirus containing the human cDNA for bcl-2, Ad.2.5HRPbcl-2. Photoreceptor-specific transgene expression was accomplished through incorporation of the 2.5 kb human rhodopsin upstream fragment (HRP). Ad.2.5HRPbcl-2 was injected alone or in combination with Ad.CMVPDE beta. Ad.CMVPDE beta contains a cDNA encoding the beta subunit of cGMP phosphodiesterase (PDE beta). Recombinant viruses containing lacZ (driven either by the cytomegalovirus (CMV) promoter/enhancer or HRP) and of Ad.CMVPDE beta and vehicle alone were injected in contralateral eyes as control. Injection of Ad.2.5HRPbcl-2 in the rd mouse resulted in histologically detectable rescue lasting 6 weeks after birth. Extent of rescue was not as large as after delivery of wildtype PDE beta, the gene defective in the rd mouse. However, delivery of genes which prevent apoptotic cell death may have broad application to gene therapy of retinal degenerative diseases.