Citations

The risk of falling reportedly increases almost 2.5-times in those with lower extremity osteoarthritis (OALE) compared with age-matched controls. However, the mechanisms underlying the increased risk are not clear. The risk factors for falls in people with OALE found in the literature are mostly the same as the risk factors for people without OALE. It is hypothesized that risk factors for falls are exacerbated by OALE, such that these individuals are more likely to become dynamically unstable and, once this has occurred, are less able to perform an appropriate compensatory stepping response compared with people without OALE. To the extent that this is true, task-specific training targeting the compensatory step, which decreases falls in middle-aged and older women, should be effective for people with OALE. The purpose of the present review is to provide the rationale for the above hypothesis. Furthermore, the present authors present evidence that the fall risk of people with OALE could be efficiently and effectively reduced using task-specific training previously shown to reduce falls in middle aged and older women.

BACKGROUNDCommunity‐acquired pneumonia (CAP) is a leading cause of morbidity and mortality among adults. Although steroids appear to be beneficial in animal models of CAP, clinical trial data in humans are either equivocal or conflicting.PURPOSEOur purpose was to perform a systematic review and meta‐analysis of studies examining the impact of steroid therapy on clinical outcomes among adults admitted with CAP.DATA SOURCES AND STUDY SELECTIONWe identified randomized controlled trials (RCTs) through a systematic search of published literature up to July 2011.DATA EXTRACTIONWe estimated relative risks (RR) and weighted mean differences, pooled from each study using a random effects model.DATA SYNTHESISEight RCTs, comprising 1119 patients, met our selection criteria. Overall quality of the studies was moderate. Adjunctive steroid therapy had no effect on hospital mortality or length of stay in the intensive care unit, but reduced the overall length of hospital stay (RR: −1.21 days [95% confidence interval (CI): −2.12 to −0.29]). Less robust data also demonstrated reduced incidence of delayed shock (RR: 0.12 [95% CI: 0.03 to 0.41]) and reduced persistence of chest x‐ray abnormalities (RR: 0.13 [95% CI: 0.06 to 0.27]). A priori subgroup and sensitivity analyses did not alter these findings.CONCLUSIONSModerate‐quality evidence suggests that adjunctive steroid therapy for adults hospitalized with CAP reduced the length of hospital stay but did not alter mortality. Journal of Hospital Medicine 2013;8:68–75. © 2012 Society of Hospital Medicine

In the care of patients with hepatic neuroendocrine metastases, medical oncologists should work in multidisciplinary fashion with surgeons, interventional radiologists, and radiation oncologists to assess the potential utility of liver-directed and systemic therapies. This paper addresses the various roles and evidence basis for cytoreductive surgery, thermal ablation (radiofrequency, microwave, and cryoablation), and embolization (bland embolization (HAE), chemoembolization (HACE), and radioembolization) as liver-directed therapies. Somatostatin analogues, cytotoxic chemotherapy, and the newer agents everolimus and suntinib are discussed as a means for controlling intra- and extrahepatic disease, along with peptide receptor radiotherapy (PRRT). Finally, the experience with orthotopic liver transplant for neuroendocrine tumors is described.

Background and objective Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. Methods We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10 −5 ) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). Results In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10 −7 ), rs981621 (p=1.65×10 −7 ) and rs16861827 (p=3.75×10 −7 ), respectively. 131 SNPs with p≤10 −5 were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10 −7 ) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. Conclusions Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.

Abstract Patients with HER-2/neu–expressing breast cancer remain at risk for relapse following standard therapy. Vaccines targeting HER-2/neu to prevent relapse are in various phases of clinical testing. Many vaccines incorporate the HER-2/neu HLA-A2–binding peptide p369–377 (KIFGSLAFL), because it has been shown that CTLs specific for this epitope can directly kill HER-2/neu–overexpressing breast cancer cells. Thus, understanding how tumors process this epitope may be important for identifying those patients who would benefit from immunization. Proteasome preparations were used to determine if p369–377 was processed from larger HER-2/neu–derived fragments. HPLC, mass spectrometry, cytotoxicity assays, IFN-γ ELISPOT, and human breast cancer cell lines were used to assess the proteolytic fragments. Processing of p369–377 was not detected by purified 20S proteasome and immunoproteasome, indicating that tumor cells may not be capable of processing this Ag from the HER-2/neu protein and presenting it in the context of HLA class I. Instead, we show that other extracellular domain HER-2/neu peptide sequences are consistently processed by the proteasomes. One of these sequences, p373–382 (SLAFLPESFD), bound HLA-A2 stronger than did p369–377. CTLs specific for p373–382 recognized both p373–382 and p369–377 complexed with HLA-A2. CTLs specific for p373–382 also killed human breast cancer cell lines at higher levels than did CTLs specific for p369–377. Conversely, CTLs specific for p369–377 recognized p373–382. Peptide p373–382 is a candidate epitope for breast cancer vaccines, as it is processed by proteasomes and binds HLA-A2.

Object Optimum management for elderly patients with newly diagnosed glioblastoma (GBM) in the temozolomide (TMZ) era is not well defined. The object of this study was to clarify outcomes in this population. Methods The authors retrospectively reviewed 105 consecutive cases involving elderly patients (age ≥ 65 years) with newly diagnosed GBM who were treated at the Mayo Clinic between 2003 and 2008. Results The patients' median age was 74 years (range 66–87 years), and the median Karnofsky Performance Status (KPS) score was 80 (range 40–90). Half of the patients underwent biopsy and half underwent resection. Patients with deep-seated lesions (19 patients [18%]) or multifocal lesions (34 patients [32%]) were more likely to have biopsy than resection (p = 0.0001 and 0.0009, respectively). New persistent neurological deficits developed in 7 patients (6.7%). Postoperative hemorrhage occurred in 6 patients (5.7%), all of whom underwent biopsy. Complete follow-up data regarding adjuvant treatment was available in 84 patients. Forty-one (49%) were treated with chemotherapy (mostly TMZ) and radiation therapy (RT), and 23 (27%) with RT alone. Nineteen (23%) received only palliative care after surgery (more common with biopsy, p = 0.03). Chemotherapy complications occurred in 28.6% (Grade 3 or 4 hematological complications in 11.9%). The median values for progression-free survival (PFS) and overall survival (OS) were 3.5 and 5.5 months. In a multivariate analysis, younger age (p = 0.03, risk ratio [RR] 0.34, 95% CI 0.13–0.89), single lesion (p = 0.02, RR 0.51, 95% CI 0.30–0.89), resection (p = 0.04, RR 0.54, 95% CI 0.31–0.94), and adjuvant treatment (p = 0.0001, RR 0.24, 95% CI 0.11–0.49) were associated with better OS. Only adjuvant treatment was significantly associated with prolonged PFS (p = 0.0007, RR 0.27, 95% CI 0.13–0.57). With combined therapy with resection, RT, and chemotherapy, the median PFS and OS were 8 and 12.5 months, respectively. Conclusions The prognosis for GBM worsens with increasing age in elderly patients. With important risks, resection and adjuvant treatment are associated with prolonged survival. Although selection bias cannot be excluded in this retrospective study, advanced age alone should not necessarily preclude optimal resection followed by adjuvant radiochemotherapy.

SummaryStem cells live long lives, renew themselves, and differentiate into more mature, less potent, specialized cells, such as epidermal keratinocytes and dermal fibroblasts. Stem cells can be embryonic, if derived from an embryo, or adult/somatic if derived from postembryonic tissue. By producing new skin cells, stem cell division and differentiation can potentially rejuvenate skin and restore hair. To reproduce, stem cells can undergo symmetric nondifferentiative or differentiative divisions, or asymmetric differentiative divisions. Asymmetric divisions reproduce the stem cell and provide a more differentiated, but less potent transient amplifying cell. Divisions and differentiation of transient amplifying cells regenerate tissues by producing cells of a specific lineage, for example, keratinocytes. Epidermal stem cells lie in niches in the interfollicular epidermis, sebaceous gland, and in the bulge regions of hair follicles. These epidermal stem cells renew the epidermis, the sebaceous glands, and hair follicles after mature cells die. Dermal stem cells lie in the hair papillae, around pericytes, and elsewhere among other dermal cells. These form pericytes, myoblasts, fibroblasts, chondrocytes, and other specialized dermal cells. Along with other signaling pathways, the Wnt signaling pathway controls stem cell fate. Wnt signals enlist two functionally and chemically different gene coactivators to direct the time and type of replicative divisions. Stem cells may help to heal wounds, repair damaged tissues, regenerate aged skin, and reinvigorate growth of skin, hair, nails, and mucous membranes.