Rural barriers to early lung cancer detection: Exploring access to lung cancer screening programs in New Hampshire and Vermont

BackgroundRural populations face many health disadvantages compared to urban areas. There is a critical need to better understand the current lung cancer screening landscape in these communities to identify targeted areas to improve the impact of this proven tool.MethodsData from the County Health Rankings of New Hampshire and Vermont was reviewed for population density, distribution of adult smokers, and level of education compared to the distribution of Lung Cancer Screening Facilities throughout these two states.ResultsScreening programs in southern counties of Vermont with lower levels of education have decreased access. In New Hampshire, there are no programs within 30 miles of the areas with the largest distribution of smokers, and decreased access in some areas with the lowest levels of education.ConclusionsImproving equitable access to high-quality screening services in rural regions and the creation of targeted interventions to address decreased access in areas of high tobacco use and low education is vital to decreasing the incidence of latestage presentations of lung cancer within these populations.     

Alemtuzumab (CAMPATH 1H) Induction Therapy in Cadaveric Kidney Transplantation—Efficacy and Safety at Five Years

Alemtuzumab is a powerful lymphocyte depleting antibody currently being evaluated in solid organ transplantation. This paper describes 5-year results of a single center study of alemtuzumab as induction in renal transplantation. Thirty-three renal transplant recipients received 20 mg alemtuzumab on day 0 and 1, followed by half-dose cyclosporin monotherapy (trough concentration 75-125 ng/mL) from day 3. They were compared in a retrospective contemporaneous-controlled manner with 66 kidney transplant recipients transplanted in the same period and center who received conventional immunosuppression with cyclosporin, azathioprine and prednisolone. In the alemtuzumab group 12% of recipients died compared to 17% in the control group (p = 0.48); likewise graft loss was similar in both groups (21% vs. 26%, respectively, p = 0.58). Incidence of acute rejection was also comparable at 5 years (31.5% vs. 33.6%), although the pattern of rejection was different with 14% patients in the alemtuzumab group experiencing rejection over 1 year post-transplant compared to none in the control group. There was no significant difference between groups in terms of infection or serious adverse events. While acknowledging the limitations of a relatively small single-center study, results suggest that alemtuzumab induction allowed satisfactory long-term patient and graft survival equivalent to that seen with standard triple immunosuppression, while avoiding steroid therapy.     

Assessment of costs to donor hospitals for organ transplantation

In 1987, die Department of Health in the UK set up a working party to identify reasons contributing to a shortfall in donor organs. One recommendation was reimbursement to the District Health Authorities for costs incurred in providing the donor organs. The figure chosen was not to be seen as an incentive to donate organs, merely as an appropriate compensation for the costs incurred. There would be no direct payment to doctors, trustees or relatives of the donor. With the development of the competitive health care environment in the United Kingdom, the reimbursement of donating hospital costs is being considered with these data.     

Modification of calcium flux of twitch skeletal muscle in mice subjected to 20% body surface area burn.

One systemic effect of burn trauma is skeletal muscle weakness. This is the result of changes in second messenger systems involving calcium (Ca2+). Kinetic analysis of Ca2+ from cellular compartments of skeletal muscle of mice that were subjected to small burn injury (20% body surface area) was performed. Muscles of the burn group showed an increased 45Ca2+ uptake maxima compared with those of time-matched control groups. Also, 45Ca2+ efflux analysis showed a lack of differentiation between electrically stimulated tissues and nonstimulated tissues that was easily observed in time-matched control groups. This lack of differentiation indicated changes in intracellular compartmentation. It can be speculated that burn trauma may have a regulatory role in the excitation-contraction coupling mechanism by altering myoplasmic levels of Ca2+ even before skeletal muscle dysfunction occurs. These findings suggest that agents capable of controlling myoplasmic Ca2+ levels may aid in alleviating chronic skeletal muscle dysfunction in patients with burns.     

Campath-1M--prophylactic use after kidney transplantation. A randomized controlled clinical trial

Campath-1M is a rat monoclonal IgM antibody that binds human complement and recognizes virtually all peripheral human mononuclear cells. It is known to be effective in T cell depletion of bone marrow grafts, and encouraging results were obtained in a pilot study in which the antibody was used in prevention and treatment of rejection of kidney, pancreas, and liver allografts. In this randomized controlled clinical trial, Campath-1M has been evaluated as a prophylactic agent following renal allografting. It is shown that patients who received a 10-day course of the antibody immediately postoperatively, in addition to standard therapy with high-dose cyclosporine (17 mg/kg), experienced a significantly lower incidence of early acute cellular rejection than control patients who received cyclosporine alone. There was no evidence of "rebound" rejection following the end of antibody treatment to suggest that rejection had merely been delayed. However, patients who received this additional immunosuppression experienced a significantly higher incidence of serious infections than controls, this negating any benefit from the treatment in terms of graft survival. Thus, a monoclonal antibody of broad specificity directed against lymphocytes may be effective as a prophylactic agent after organ transplantation but its use should be accompanied by a reduction in other immunosuppressive drugs.     

Phenotype delineation of ZNF462 related syndrome

Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79%) and a minority has autism spectrum disorder (33%). Characteristic facial features include ptosis (83%), down slanting palpebral fissures (58%), exaggerated Cupid's bow/wide philtrum (54%), and arched eyebrows (50%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25% of individuals, hypotonia in half, and structural heart defects in 21%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features.     

gp49B1 suppresses stem cell factor-induced mast cell activation-secretion and attendant inflammation in vivo

We report that gp49B1, a mast cell membrane receptor with two immunoreceptor tyrosine-based inhibitory motifs (ITIM), constitutively inhibits mast cell activation-secretion induced by stem cell factor (SCF), a tissue-derived cytokine that also regulates mast cell development. The intradermal injection of SCF into the ears of gp49B1 null (gp49B(-/-)) mice elicited approximately 4- and 2.5-fold more degranulating mast cells and tissue swelling caused by edema, respectively, than in gp49B(+/+) mice. SCF did not induce tissue swelling in mast cell-deficient mice, and the responsiveness of gp49B(-/-) mice to mast cell-associated amine and lipid mediators was unaltered. When gp49B(+/+) and gp49B(-/-) mice were pretreated with antagonists of the amines, SCF-induced tissue swelling was reduced by >90% and 60%, respectively, and it was reduced by >90% in both genotypes when a cysteinyl leukotriene receptor antagonist was also provided. Hence, the dominant contribution of secretory granule amines to SCF-induced tissue swelling is the result of gp49B1-mediated inhibition of the production of cysteinyl leukotrienes by mast cells. Our findings also provide the first example of an ITIM-bearing receptor that constitutively suppresses inflammation generated in vivo independently of the adaptive immune response by a receptor that signals through intrinsic tyrosine kinase activity rather than immunoreceptor tyrosine-based activation motifs.