Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners.

Systemic sclerosis (SSc) is a rare disabling autoimmune disease with a similar mortality to many cancers. Two randomized controlled trials of autologous hematopoietic stem cell transplantation (AHSCT) for SSc have shown significant improvement in organ function, quality of life and long-term survival compared to standard therapy. However, transplant-related mortality (TRM) ranged from 3-10% in patients undergoing HSCT. In SSc, the main cause of non-transplant and TRM is cardiac related. We therefore updated the previously published guidelines for cardiac evaluation, which should be performed in dedicated centers with expertize in HSCT for SSc. The current recommendations are based on pre-transplant cardiopulmonary evaluations combining pulmonary function tests, echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic testing, initiated at Northwestern University (Chicago) and subsequently discussed and endorsed within the EBMT ADWP in 2016.

Improving operating room first start efficiency - value of both checklist and a pre-operative facilitator.

BACKGROUND: There are multiple components leading to improved operating room efficiency. We undertook a project focusing on first case starts; accounting for each delay component on a global basis. Our hypothesis was there would be a reduction in first start delays after we implemented strategies to address the issues identified through this accounting process. METHODS: An orange sheet checklist was implemented, with specific items that needed to be clear prior to roll back to the operating room (OR), and an OR facilitator was employed to intervene whenever there were any missing items needed for a specific patient. We present the data from this quality improvement project over an 18-month period. RESULTS: Initially, 10.07 (± 0.73) delayed first starts occurred per day but declined steadily over time to a low of 4.95 (± 0.38) per day after 6 months (-49.2 %, P < 0.001). By the end of the project, the most common reasons for delay still included late surgical attending (19%), schedule changes (14%) as well as 'other reasons' (13%), but with an overall reduction per day of each. Total anaesthesia delay initially totalled 11% of the first start delays, but was negligible (< 1%) at the project's completion. CONCLUSIONS: While we have a challenging operating room environment based on our patient population, multiple trainees in both the surgery and anaesthesiology teams: an orange sheet - pre-operative checklist in addition to a dedicated pre-operative facilitator; allowed us to make a substantial improvement in our first start on time starts.

Effects of ultra-wideband electromagnetic pulses on pre-neoplastic mammary epithelial cell proliferation.

Electromagnetic ultra-wideband pulses (UWB) or nanopulses, are generated by a wide range of electronic devices used in communications and radar technology. However, the specific effects of nanopulse exposure on cell growth and function have not been extensively investigated. Here, studies have been conducted to determine the effects of prolonged exposure to non-ionizing, low to moderate intensity nanopulses on the growth of pre-neoplastic CL-S1 mammary epithelial cells in vitro. Cells were grown in culture and maintained in serum-free defined medium containing 10 ng/ml EGF and 10 microg/ml insulin as comitogens. Studies showed that 0.25-3.0 h exposure to nanopulses of 18 kV/m field intensity, 1 kHz repetition rate and 10 ns pulse width had no effect on CL-S1 cell growth or viability during the subsequent 72-h culture period. However, exposure to similar nanopulses for prolonged periods of time (4-6 h) resulted in a significant increase in cell proliferation, as compared to untreated controls. Additional studies showed that nanopulse exposure enhanced CL-S1 cell growth when cells were maintained in media containing only EGF, but had no effect on cells maintained in defined media that were mitogen-free or containing only insulin. Studies also showed that the growth-promoting effects of nanopulse exposure were associated with a relatively large increase in intracellular levels of phospho-MEK1 (active) and phospho-ERK1/2 (active) in these cells. These findings demonstrate that prolonged exposure to moderate levels of UWB enhanced EGF-dependent mitogenesis, and that this growth-promoting effect appears to be mediated by enhanced activation of the mitogen-activated protein kinase (MAPK) signalling pathway in pre-neoplastic CL-S1 mammary epithelial cells.

Relationship of p15 and p16 gene alterations to elevated dihydrofolate reductase in childhood acute lymphoblastic leukaemia.

The downstream effects of p15 and p16 gene deletions and loss of transcripts on dihydrofolate reductase (DHFR) were examined in 63 B-precursor (BP) acute lymphoblastic leukaemia (ALL) samples. p15 and/or p16 gene deletions were seen in 6% and 8%, respectively, of BP-ALL samples; however, losses of p15 and/or p16 transcripts were seen in 26 out of 63 (41%) samples. Loss of p15 transcripts (36.5%) exceeded that for p16 (17.5%). For the 26 BP-ALLs that lacked p15 and/or p16 transcripts, only six (23%) exhibited low levels of DHFR by flow cytometry assay with Pt430, a fluorescent anti-folate. Conversely, 18 out of 37 (49%) BP-ALL samples with intact p15 and/or p16 genes and transcripts showed low levels of DHFR (P = 0.04). In p15- and p16-null K562 cells transfected with a tetracycline-inducible p15 cDNA construct, induction of p15 transcripts and protein was accompanied by decreased growth rates, decreased S-phase fraction, decreased retinoblastoma protein phosphorylation, and markedly reduced levels of DHFR transcripts and protein. Collectively, our results suggest that losses of p15 and/or p16 gene expression result in elevated levels of DHFR in BP-ALL in children. However, additional downstream factors undoubtedly also contribute to elevated levels of this enzyme target.

Rates of lower-extremity amputation and arterial reconstruction in the United States, 1979 to 1996.

OBJECTIVES: This report describes trends in the rates of lower-extremity amputation and revascularization procedures and vascular disease risk factors. METHODS: We analyzed trends in National Hospital Discharge Survey data for 1979 through 1996 and in National Health Interview Study data for 1983 through 1994. RESULTS: Despite a decline between 1983/84 and 1991/92, by 1995/96 the rate of major amputation had increased 10.6% since 1979/80. The earlier 12-year decline was positively correlated with reductions in the prevalence of smoking (r = 0.88, P < .0001), hypertension (r = 0.65, P = .02), and heart disease (r = 0.73, P = .007), but not diabetes (r = -0.33, P = .29). During the 1980s, amputation and angioplasty rates were inversely correlated (r = -0.75, P = .001), but the decline in amputation rates occurred before the increase in angioplasty. The major amputation rate, which has increased since 1993, was 24.95 per 100,000 people in 1996. CONCLUSIONS: Major amputation rates fell in the years following the diffusion of distal bypass surgery but before the widespread use of peripheral angioplasty. Because disease prevalence and primary amputation rates are unknown, it is difficult to estimate the contribution of recent improvements in vascular surgery to limb preservation.

Primary malignant fibrous histiocytoma of the lung in a child: a case report and review of literature.

Malignant fibrous histiocytoma (MFH), an aggressive high-grade soft tissue sarcoma, usually occurs in the elderly during the fifth to seventh decade of life. It commonly arises in the retroperitoneum, extremities, and head and neck region. Primary pulmonary MFH is extremely rare and is frequently fatal. We present the youngest known case, a 9-year-old boy with a primary left lung grade II inflammatory MFH, stage II. He underwent a left upper lobectomy for tumor resection. After completing radiation therapy, he was started on vincristine, actinomycin D, and cyclophosphamide alternating with vincristine, doxorubicin, and cyclophosphamide every 3 weeks. After five such cycles, he had a histologically proven local recurrence. He then received chemotherapy consisting of ifosfamide (2 g/m2) and etoposide (VP-16) (100 mg/m2) given daily for 3 days every 3 weeks. The patient attained complete remission (CR) after five such cycles and completed treatment without any major complications. He received a total of 16 courses and is continuing in CR 36 months off treatment. Ifosfamide and etoposide (VP-16), known for their usefulness in treatment of adult soft tissue sarcomas, can be used as salvage chemotherapy for patients with MFH who fail the front-line conventional chemotherapy.

Immune thrombocytopenia and hemolytic anemia associated with Hodgkin disease.

PURPOSE: We discuss an unusual clinical presentation of Hodgkin disease with immune thrombocytopenia and autoimmune hemolytic anemia. PATIENTS AND METHODS: A 4-year-old boy presented to us with a large anterior mediastinal mass, thrombocytopenia, and Coombs' positive hemolytic anemia refractory to transfusion therapy. Biopsy of the anterior mediastinal mass was possible only after administration of intravenous immunoglobulin to raise the platelet count. The immune manifestations decreased with initiation of appropriate chemotherapy. RESULT: The child was able to successfully complete chemotherapy and radiation therapy and has no clinical or laboratory evidence of persistent autoimmune phenomena. CONCLUSION: Immune thrombocytopenia with autoimmune hemolytic anaemia is a rare presenting manifestation of Hodgkin disease and can present difficulty in diagnosis and management.