Is Norton Score a useful tool for identifying high-risk patients prior to emergency surgery?

BACKGROUND: Emergency surgery in elderly patients is associated with high mortality rates. Various scoring systems may be valuable in predicting mortality and morbidity rates. It has been suggested that the Norton Score (NS) could be used to quantify frailty. We hypothesized that NS could be a useful tool for identifying high-risk patients before emergency/urgent surgeries. METHODS: A retrospective study was conducted in the Department of Surgery at Kaplan Medical Center, Rehovot, Israel. INCLUSION CRITERIA: age ≥50 years, American Society of Anesthesiologists (ASA) physical status score ≥3 and urgent/emergency laparotomy. A total of 400 patients were identified, and 150 (37.5%) matched the inclusion criteria. RESULTS: A total of 150 patients with ASA scores of 3-5 and who underwent emergent/urgent laparotomy from 1 January 2011 through 31 January 2013 were included. Mean age was 77 ± 9.7 years. The mortality rate at 1 month was 44% (66 patients) and at 1 year was 54.7% (82 patients). A higher ASA score was significantly associated with mortality (P < 0.001). Survivors had lower frailty scores and presented significantly higher preoperative NS (Modified Frailty Index 2.45 versus 3.06, P < 0.05; NS 16.09 versus 12.94, P < 0.01). Preoperative NS was the most significant variable that predicted poor patient prognosis (odds ratio 0.84; 95% confidence interval 0.73-0.96). For ASA 3 and ASA 4, the grade of daily personal independence in activities showed a positive correlation with survival (P < 0.001). CONCLUSION: NS can be a very useful and quick tool to evaluate surgical risk in emergency surgery. Our study supports the use of NS in the perioperative evaluation prior to emergency surgery.

Evaluation and Predictors for Nasogastric Tube Associated Pressure Ulcers in Critically Ill Patients.

BACKGROUND: Nasal device-related pressure ulcers are scarcely addressed in the literature. OBJECTIVES: To assess the prevalence and severity of cutaneous and mucosal nasogastric tube (NGT)-associated pressure ulcers (PU) in critically ill patients and to define predictors for their formation. METHODS: A single center observational study of intensive care unit patients with a NGT for more than 48 hours was conducted. Nasal skin was evaluated for PU. Ulcers were graded according to their depth. Consenting patients underwent a nasoendoscopic examination to evaluate intranasal mucosal injury. RESULTS: The study comprised 50 patients, 17 of whom underwent nasoendoscopic examination. Mean time of NGT presence in the nose was 11.3 ± 6.17 days. All patients had some degree of extranasal PU, 46% were low grade and 54% were high grade. Predictors for high grade extranasal PU compared to low grade PU were higher peak Sepsis-related Organ Failure Assessment (SOFA) scores (11.52 vs. 8.87, P = 0.009), higher peak C-reactive protein (CRP) levels (265.3 mg/L vs. 207.58, P = 0.008), and bacteremia (33.3% vs. 8.7%, P = 0.037). The columella was the anatomical site most commonly involved and the most severely affected. The number of intranasal findings and their severity were significantly higher in the nasal cavity containing the NGT compared to its contralateral counterpart (P = 0.039 for both). CONCLUSIONS: NGTs cause injury to nasal skin and mucosa in critically ill patients. Patients with bacteremia, high CRP, and high SOFA scores are at risk for severe ulcers, warranting special monitoring and preventive measures.

Assessment of aortic stiffness among patients with systemic lupus erythematosus and rheumatoid arthritis by magnetic resonance imaging.

To evaluate aortic stiffness by MRI in female patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in comparison to controls. We measured aortic strain, distensibility and pulse wave velocity (PWV) by MRI in 30 SLE patients, 31 RA patients and 53 matched controls. Mean PWV in SLE and RA patients were higher in comparison to controls (9.2 ± 4.4 vs. 7.6 ± 3.0 m/s, p = 0.04) and (6.2 ± 2.3 vs. 5.4 ± 1.7, p = 0.04) respectively. Aortic distensibility among RA patients was significantly lower in comparison to controls (4.4 ± 4.6 vs. 5.8 ± 4.9 kPa(-1) × 10(-3), p = 0.04). A significant correlation was found between PWV and age (r = 0.67, p < 0.001), Framingham risk score (r = 0.61, p < 0.001), waist to hip ratio (r = 0.45, p < 0.001), systolic blood pressure (r = 0.37, p = 0.01), diabetes (r = 0.32, p = 0.001) and dyslipidemia (r = 0.32, p = 0.001). In multivariate analysis for the prediction of PWV, variables which were found significant included: RA (p = 0.01), age (p < 0.001) and hypertension (p = 0.01) for patients with RA and SLE (p = 0.02), waist to hip ratio (p < 0.001) and total cholesterol (p < 0.001) for patients with SLE. Arterial stiffness, characterized by metrics of aortic distensibility and pulse wave velocity derived from MRI, is increased in SLE and RA female patients.

PKCη is an anti-apoptotic kinase that predicts poor prognosis in breast and lung cancer.

The successful treatment of cancer in a disseminated stage using chemotherapy is limited by the occurrence of drug resistance, often mediated by anti-apoptotic mechanisms. Thus the challenge is to pinpoint the underlying key factors and to develop therapies for their direct targeting. Protein kinase C (PKC) enzymes are promising candidates, as some PKCs were shown to be involved in regulation of apoptosis. Our studies and others have shown that PKCη is an anti-apoptotic kinase, able to confer protection on tumour cells against stress and chemotherapy. We have demonstrated that PKCη shuttles between the cytoplasm and the nucleus and that upon DNA damage is tethered at the nuclear membrane. The C1b domain mediates translocation of PKCη to the nuclear envelope and, similar to the full-length protein, could also confer protection against cell death. Furthermore, its localization in cell and nuclear membranes in breast cancer biopsies of neoadjuvant-treated breast cancer patients was an indicator for poor survival and a predictor for the effectiveness of treatment. PKCη is also a novel biomarker for poor prognosis in non-small-cell lung cancer (NSCLC). Thus PKCη presents a potential target for therapy where inhibition of its activity and/or translocation to membranes could interfere with the resistance to chemotherapy.

Ethnicity and sepsis characteristics and outcomes. Population based study.

BACKGROUND: Two distinct ethnic groups live in Southern Israel: urban Jews and rural Bedouin Arabs. These groups differ in their socioeconomic status, culture and living environment, and are treated in a single regional tertiary care hospital. We hypothesized that these two ethnic groups have different patterns of sepsis-related intensive care admissions. METHODS: The study included all adult patients admitted to the Soroka University Medical Center Intensive Care Units between January 2002 and December 2008, with a diagnosis of sepsis. Demographic data, medical history, and hospitalization and outcomes data were obtained. Primary outcome was all-cause mortality. RESULTS: Jewish patients admitted to the ICU (1343, 87%) were on average 17 years older than Bedouin Arabs (199, 13%). For the population <65 years, Bedouin Arabs had slightly higher age-adjusted prevalence of ICU sepsis admissions than Jewish patients (39.5 vs. 43.0, p=0.25), while for the population >65 years there was a reverse trend (21.8 vs. 19.8 p=0.49). There were no differences in the type of organ failure, sepsis severity or length of hospitalization between the two groups. Twenty eight days/in-hospital mortality was 33.9% in Bedouin Arabs vs. 45.5% in Jews, p=0.004. Following adjustment for comorbidities, age and severity of the disease, survival was unrelated to ethnicity, both at 28 days (odds ratio for Bedouin Arabs 0.86, 95% CI 0.66-1.24) and following hospital discharge (hazard ratio 0.86, 95% 0.67-1.09). CONCLUSIONS: Sepsis-related ICU admissions are more prevalent among Bedouin Arabs at younger age compared with the Jewish population. Adjusted for confounders, ethnicity does not influence prognosis.

Localization of PKCη in cell membranes as a predictor for breast cancer response to treatment.

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: 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: 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.

Syphilis and HIV co-infection.

Syphilis is a complex disease, which is sexually transmitted. The incidence of syphilis is rising all over the world, partly due to the increased transmission in HIV patients and other high risk groups such as men who have sex with men. Interestingly syphilis itself facilitates HIV infection in several ways. Great importance exists in recognition of both diseases and their complex interactions. This article will review the manifestations of syphilis in the context of HIV infected patients, and the challenging diagnosis and management of these patients.

Onset of late posttraumatic seizure after dehydroepiandrosterone treatment.

OBJECTIVE: To describe the first reported case of a seizure in a patient using the dietary supplement DHEA in an attempt to improve ovarian oocyte production. DESIGN: Case report. SETTING: University-affiliated teaching hospital, neurologic department. PATIENT(S): A 30-year-old woman with fragile X syndrome and no history of any convulsive disorder who was receiving IVF treatment. INTERVENTION(S): Daily treatment with the dietary supplement DHEA. MAIN OUTCOME MEASURE(S): Generalized seizure. RESULT(S): After 1 month of DHEA treatment, the patient was admitted with a generalized seizure. CONCLUSION(S): A generalized seizure, associated with concurrent intake of DHEA.

Hormonal regulation of PKC: estrogen up-regulates PKCeta expression in estrogen-responsive breast cancer cells.

Protein kinase C (PKC) is involved in several major signal transduction pathways that control gene expression cell growth and differentiation. The PKCeta isoform appears as a candidate regulator of mammary gland proliferation or differentiation, as its expression is up-regulated in the mammary gland in the transit from resting to the pregnant state. The purpose of this study was to examine the hormonal regulation of PKCeta. Here we show that estradiol specifically up-regulates the expression of PKCeta in the estrogen-responsive lines MCF-7 and T47D but not in the estrogen non-responsive line MDA-MB 231. Interestingly, the presence of progesterone, involved in the differentiation of the mammary gland, reduced the estrogen-induced PKCeta expression in a time-dependent manner. Thus, our studies suggest that PKCeta has an important role in signalling pathways regulating mammary gland proliferation and its development.