New concepts in the prevention of pressure sores.

Pressure sores are a serious, and costly, complication for many patients with reduced mobility and sensation. Some populations, such as those with spinal cord injury (SCI), remain at high risk throughout their lifetime. Prevention is highly preferable and while the concept is readily definable, it is much more challenging to develop valid preventative measures. Subjective and objective approaches to risk factor assessment before pressure sores develop are reviewed, including risk status scales and emerging techniques to assess deep tissue injury. Devices to prevent pressure sores have traditionally focused on pressure-relieving cushions and mattresses. Technological advances being applied in the development of new pressure sore prevention devices are presented. Clinical evidence-based practice is integral to pressure sore prevention. Comprehensive assessment must include evaluation of systemic diseases, anatomical and physiological factors, together with environmental and psychosocial factors, which can all contribute to pressure sore development. Extrinsic factors need to be considered in conjunction with intrinsic tissue health factors and are reviewed together with an evaluation of currently available clinical practice guidelines. This chapter presents the broad diversity of factors associated with pressure sore development and highlights the need for an interdisciplinary team approach in order to maximize successful prevention of pressure sores.

Poor nutrition is a relative contraindication to negative pressure wound therapy for pressure ulcers: preliminary observations in patients with spinal cord injury.

OBJECTIVE: To assess the efficacy of negative-pressure wound therapy (NPWT) for healing of pressure ulcers (PrUs) in individuals with spinal-cord injury (SCI). DESIGN: Multicenter, 28-day observational study. SETTING: Ten Veterans Affairs Medical Center SCI centers. PATIENTS: Eighty-six SCI inpatients with Stage III/IV pelvic PrUs. INTERVENTIONS: Standard wound care with NPWT versus standard wound care alone (NoNPWT). MAIN OUTCOME MEASURES: Change in wound surface area (WSA) using the Verg Videometer Measurement Documentation software. MAIN RESULTS: The proportion of patients demonstrating a decrease in WSA (healing subgroup) was not significantly different between the NPWT (n = 33) and NoNPWT (n = 53) groups (67% vs 70%, respectively). In the healing subgroup, there was no significant difference between the NPWT versus NoNPWT groups in WSA decrease (-43 ± 22% vs -50% ± 26%, not statistically significant). Similarly, in the nonhealing subgroup, there was no significant difference between NPWT and NoNPWT groups (31% ± 26% vs 32% ± 34%). In the NPWT group, the nonhealing subgroup (11/33) had significantly lower serum albumin levels than the healing subgroup (22/33) (2.9 ± 0.4 vs 3.3 ± 0.5 mg/dL, P < .05). In the NoNPWT group, there was no significant difference in serum albumin levels between the healing versus nonhealing subgroups (3.2 ± 0.3 vs 3.2 ± 0.3 mg/dL). CONCLUSION: In SCI patients with Stage III/IV pelvic PrUs, NPWT did not significantly influence the rate of healing. Additionally, in malnourished individuals (albumin <3.0 mg/dL), NPWT was not efficacious. Healing outcomes in the NPWT group were significantly influenced by albumin levels, whereas no such disparity was noted between the healing and nonhealing PrUs for the NoNPWT group. Nutritional status appears to be important in the effectiveness of NPWT.

The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes.

A somatic mutation in the JH2 autoinhibitory domain of the Janus kinase 2 (JAK2) tyrosine kinase was recently described in polycythemia vera, essential thrombocythemia, and myelofibrosis with myeloid metaplasia. The prevalence of this mutation in either "atypical" myeloproliferative disorders (MPDs) or the myelodysplastic syndromes (MDSs) is unknown. Bone marrow-derived genomic DNA from 245 patients--119 with chronic myelomonocytic leukemia (CMML), 101 with MDS, 11 with hypereosinophilic syndrome (HES), 8 with systemic mastocytosis (SM), and 6 with chronic neutrophilic leukemia (CNL)--was screened for the JAK2 V617F mutation. A mutant allele was detected in 11 patients: 3 with CMML (3%), 5 with MDS (5%), 2 with SM, and 1 with CNL. Interestingly, one of the patients with SM and the patient with CNL with JAK2 V617F had a history of lymphoma, and this patient with SM also had associated myelofibrosis and CMML. The current observation strengthens the specific association between JAK2 V617F and classic MPD, but also suggests an infrequent occurrence in other myeloid disorders.

Heat shock protein 90 inhibition sensitizes acute myelogenous leukemia cells to cytarabine.

Previous studies demonstrated that ataxia telangiectasia mutated- and Rad3-related (ATR) kinase and its downstream target checkpoint kinase 1 (Chk1) facilitate survival of cells treated with nucleoside analogs and other replication inhibitors. Recent results also demonstrated that Chk1 is depleted when cells are treated with heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). The present study examined the effects of 17-AAG and its major metabolite, 17-aminogeldanamycin (17-AG), on Chk1 levels and cellular responses to cytarabine in human acute myelogenous leukemia (AML) cell lines and clinical isolates. Cytarabine, at concentrations as low as 30 nM, caused activating phosphorylation of Chk1, loss of the phosphatase Cdc25A, and S-phase slowing. Conversely, treatment with 100 to 300 nM 17-AAG for 24 hours caused Chk1 depletion that was accompanied by diminished cytarabine-induced S-phase accumulation, decreased Cdc25A degradation, and enhanced cytotoxicity as measured by inhibition of colony formation and induction of apoptosis. Additional studies demonstrated that small inhibitory RNA (siRNA) depletion of Chk1 also sensitized cells to cytarabine, whereas disruption of the phosphatidylinositol 3-kinase (PI3k) signaling pathway, which is also blocked by Hsp90 inhibition, did not. Collectively, these results suggest that treatment with 17-AAG might represent a means of reversing checkpoint-mediated cytarabine resistance in AML.

The effect of family and peer communication on college students' communication with dating partners about HIV and AIDS.

As family and peers are primary socializing agents in the lives of young adults, a social learning based model of communication about HIV/AIDS among dating partners was developed and tested, examining the role of interactions with family and peers in this type of communication. Specifically, the model describes relationships between general communication, communication about sexuality, and communication about HIV/AIDS with parents, peers, and dating partners. Participants were 153 young adult couples who completed measures of their communication practices, as well as their communication with family and peers. Communication practices in the family of origin appear to influence both general communication and communication about HIV/AIDS with dating partners. Communication practices with peers influenced general communication, communication about sexuality, and communication about HIV/AIDS with dating partners. Participants and their dating partners exhibited relative agreement about their general communication practices and their communication about HIV/AIDS, but showed less agreement in reports of their communication about sexuality. Implications for understanding the role of family and peer interactions in communication about HIV/AIDS with dating partners are discussed.