Faculty Bibliography

INTRODUCTION/BACKGROUND:Choosing the right burn patient that transfers to a rehabilitation facility following acute hospitalization is a difficult decision. In our study we characterize demographic, injury and hospitalization related variables that predict a burn patient's transfer to a rehabilitation facility. METHODS:We analyzed the data of 974 burn patients with burns of the second degree and deeper, spanning 20% TBSA (total body surface area) or more, that were admitted to all 5 hospitals that operate a burn unit in Israel, between the years 1998 and 2005. RESULTS:The results of the multivariate logistical regression model in which the predicted variable is discharge to rehabilitation showed that the most predictive variables were inhalation injury, surgical procedures and hospitalization period. Execution of a surgical procedure was the most influential factor over discharge to rehabilitation (odds ratio=6.202) followed by inhalation injury (OR=4.706) and finally, the hospitalization period (OR=1.026) (an increase of 1.026 times in the likelihood to be sent to rehabilitation with any additional day of hospitalization). DISCUSSION/CONCLUSIONS:In this study we examined patients who were sent to a rehabilitation facility upon completion of their acute care in an attempt to evaluate common initial clinical variables that assist in making an educated decision regarding the patient rehabilitation transfer. This is one of the first attempts at examining and revealing evidence based parameters that might determine the correct burn patient to send to rehabilitation after his hospitalization.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Parapharyngeal space (PS) tumors are surrounded by critical anatomical structures. Resection is often challenging due to limited surgical exposure. Herein, we report a novel transcervical, minimally invasive, video-assisted technique that facilitates the resection of PS lesions. STUDY DESIGN/METHODS:Case series and review of literature. METHODS:Description of surgical technique with analysis of four cases and literature review. RESULTS:The technique combines a transcervical approach to the PS and skull base with video-assisted and image-guided dissection of tumor. Four cases of benign PS tumors resected with this technique are reported. The size of the tumor excised varied between 0.9 cm and 5 cm. Estimated blood losses were minimal. The average length of hospital stay was 1.5 days. No permanent complications were encountered. CONCLUSIONS:Excision of PS tumor abutting the skull base using a novel minimally invasive, video-assisted, image-guided, transcervical approach is feasible and safe. The short hospitalization stay and low morbidity makes it well suited for the resection of benign PS lesions.

Cancer stem cell behavior is thought to be largely determined by intrinsic properties and by regulatory signals provided by the microenvironment. Myelofibrosis (MF) is characterized by hematopoiesis occurring not only in the marrow but also in extramedullary sites such as the spleen. In order to study the effects of these different microenvironments on primitive malignant hematopoietic cells, we phenotypically and functionally characterized splenic and peripheral blood (PB) MF CD34+ cells from patients with MF. MF spleens contained greater numbers of malignant primitive HPCs than PB. Transplantation of PB MF CD34+ cells into immunodeficient (NOD/SCID/IL2Rγ(null)) mice resulted in a limited degree of donor cell chimerism and a differentiation program skewed toward myeloid lineages. By contrast, transplanted splenic MF CD34+ cells achieved a higher level of chimerism and generated both myeloid and lymphoid cells that contained molecular or cytogenetic abnormalities indicating their malignant nature. Only splenic MF CD34+ cells were able to sustain hematopoiesis for prolonged periods (9 months) and were able to engraft secondary recipients. These data document the existence of MF stem cells (MF-SCs) that reside in the spleens of MF patients and demonstrate that these MF-SCs retain a differentiation program identical to that of normal hematopoietic stem cells.

Interferon (IFN-α) is effective therapy for polycythemia vera (PV) patients, but it is frequently interrupted because of adverse events. To permit the long-term use of IFN, we propose combining low doses of IFN with Nutlin-3, an antagonist of MDM2, which is also capable of promoting PV CD34(+) cell apoptosis. Combination treatment with subtherapeutic doses of Peg IFN-α 2a and Nutlin-3 inhibited PV CD34(+) cell proliferation by 50% while inhibiting normal CD34(+) cells by 30%. Combination treatment with Nutlin-3 and Peg IFN-α 2a inhibited PV colony formation by 55%-90% while inhibiting normal colony formation by 22%-30%. The combination of these agents also decreased the proportion of JAK2V617F-positive hematopoietic progenitor cells in 6 PV patients studied. Treatment with low doses of Peg IFN-α 2a combined with Nutlin-3 increased phospho-p53 and p21 protein levels in PV CD34(+) cells and increased the degree of apoptosis. These 2 reagents affect the tumor suppressor p53 through different pathways with Peg IFN-α 2a activating p38 MAP kinase and STAT1, leading to increased p53 transcription, whereas Nutlin-3 prevents the degradation of p53. These data suggest that treatment with low doses of both Nutlin-3 combined with Peg IFN-α 2a can target PV hematopoietic progenitor cells, eliminating the numbers of malignant hematopoietic progenitor cells.

PURPOSE/OBJECTIVE:To describe the prevalence of lack of prenatal care (LOPC) over the years and to examine the association between LOPC and perinatal complications among Bedouin parturients. METHODS:A retrospective study comparing all singleton births of Bedouin women with and without prenatal care, between the years 1988 and 2009, was conducted. Multiple logistic regression models were used to control for confounders. RESULTS:Out of 123,506 singleton deliveries, 16.5% (n = 20,402) were of women lacking prenatal care. A gradual increase in the rate of LOPC was noted between the years 2006 and 2009. Using multivariable analyses, controlling for parity, LOPC was found to be significantly associated with preterm delivery (PTD) < 37 weeks (odds ratio (OR) 1.13, 95% CI 1.07-1.19), PTD < 34 weeks (OR 1.53, 95% CI 1.40-1.67), low birth weight < 2,500 g (LBW; OR 1.39, 95% CI 1.32-1.46), very LBW < 1,500 g (OR 1.67, 95% CI 1.49-1.86), and perinatal mortality (OR 1.63, 95% CI 1.47-1.80). CONCLUSIONS:Lack of prenatal care in a traditional community is associated with adverse obstetric outcomes and specifically is an independent risk factor for preterm delivery, low birth weight, and perinatal mortality.

The association between chronic inflammation and carcinogenesis, as well as neoplastic progression, has been researched and is well-established. Being a central coordinator of immune responses, nuclear factor-kappa B (NFkappaB) signaling plays a critical role in cancer development and progression. The activation of the NFkappaB signaling pathway is highly monitored under normal conditions, and is mainly known as a key pathway in activation of immune responses. Constitutively active NFkappaB has been identified in most tumor cell lines, as well as in a wide variety of tumor tissues derived from cancer patients. Such activation may also affect the cancer's response to therapy, making it less susceptive to radio and chemo treatment. Hence, NFkappaB has become a target for inhibition by chemotherapeutic agents. Traditionally, medicinal herbs have been used to prevent and treat a variety of diseases, including cancer. In this article, we review several natural, herbal-derived compounds shown to have anti-inflammatory and anticancer activities mediated, at least in part, by NFkappaB signaling inhibition. Compounds of this sort may potentially serve as clinically effective anticancer treatments.

BACKGROUND:Successful treatment of breast cancer is frequently limited by the resistance of tumors to chemotherapy. Recent studies suggested a role for protein kinase C (PKC) in the resistance to chemotherapy. Here we used retrospective analysis of breast cancer biopsies of neoadjuvantly treated patients to investigate the correlation of PKC expression with aggressiveness and resistance to chemotherapy. PATIENTS AND METHODS/METHODS:Our cohort (n = 25) included patients with advanced and aggressive breast cancers, who underwent neoadjuvant therapy with the CAF regimen (cyclophosphamide, doxorubicin, fluorouracil). Core biopsies (pre-chemotherapy) and surgical biopsies of primary tumors and lymph node metastases (post-chemotherapy) were scored for PKCeta (PKCh) and PKCepsilon (PKCe) expression in the cytoplasm, cell membrane, nuclear membrane, and the nucleus. RESULTS:Our results showed increased expression of PKCh (not PKCe) in the cytoplasm and cell membranes of post-chemotherapy biopsies (p = 0.03). PKCh presence in cell membranes, indicating activation, was in correlation with poor survival (p = 0.007). CONCLUSION/CONCLUSIONS:PKCh staining in cell and nuclear membranes is an indicator for poor survival and a predictor for the effectiveness of neoadjuvant treatment. Other avenues of treatment should be considered for these patients. PKCh presents a target for therapy where inhibition of its activity and/or translocation to membranes could interfere with the resistance to chemotherapy.