Issue Information

There are limited recommendations for fasting in many chronic diseases such as adrenal insufficiency (AI). Research in such situations highlights potential for complications and need for education for patients with AI undertaking fasting during Ramadan. This article aimed to provide up-to-date guidance for healthcare professionals to educate, discuss and manage patients with AI who are considering fasting in Ramadan and is religiously compatible. Latest guidance on this topic and the evidence base for steroid dosing are reviewed and discussed. Risk stratification for patients with AI and optimal strategies for management, including steroid dosing, are detailed. Our review highlights that patients with AI wishing to fast should undergo a thorough risk assessment ideally several months before Ramadan. ‘High risk’ and ‘Very high risk’ patients should be encouraged to explore alternative options to fasting discussed below. Prior to the commencement of Ramadan, all patients must receive up-to-date education on sick day rules, instructions on when to terminate their fast or abstain from fasting, carry steroid warning information and must have a valid intramuscular (IM) hydrocortisone pack and know how to administer this. Switching patients with AI desiring to fast from multiple daily hydrocortisone replacement to prednisolone 5 mg once daily at dawn (during Suhoor or Sehri) is recommended and discussed. Patients on fludrocortisone for AI should be advised to take their total dose at dawn. We provide practically relevant case-based scenarios to help with the application of this guidance. Future efforts need to focus on healthcare professional awareness and further research in this setting.     

p21 WAF1/cip1expression in non-melanoma skin tumors

Abnormal control of the cell cycle is closely linked to carcino-genesis. p21^WAF1/CIP1 protein is a universal inhibitor of Gl cyclin-dependent kinase and is induced by p53-dependent and -independent pathways. In order to elucidate the role of p21^WAF1/CIP1 in human skin carcinogenesis, protein expression in squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), actinic keratosis (AK), keratoacanthoma (KA), seborrheic keratosis (SK), and normal skin was examined using an immunohistochemical method. In normal skin, a few positive cells were seen in some cases in the upper spinous layer of the epidermis; sebaceous glands also had positive cells. In cases of SK and KA, positive cells were found in the basal and suprabasal epidermal layers (proliferation pattern), and in cases of BD and AK, positive cells were seen mainly in the upper spinous layer (differentiation pattern). Cases of SCC had more positive cells and showed two staining patterns: proliferation, or mixed. Cases of BCC had no positive cells. p21^WAF1/CIP1 has some unidentified role in keratinocyte tumorigenesis, which may not be related directly to carcinogenesis.     

Laryngeal cancer: in relation to oxidative stress

This study was designed to investigate the oxidative stress parameters in laryngeal cancer and cancer-free adjacent tissues. Lipid peroxidation end product and the endogenous antioxidant components-CuZn superoxide dismutase (CuZn SOD) glutathione peroxidase (GSH Px), glutathione reductase (GSSG Rd) and glutathione (GSH)-were analysed by spectrophotometric and kinetic methods. Laryngeal cancer tissue exhibited higher lipid peroxidation than cancer free adjacent tissue. CuZn SOD and GSH Px activities and GSH level were significantly higher and GSSG Rd activity significantly lower in the cancer tissue. Detection of the antioxidant status may be useful to determine the tumour resistance to therapy, to choose the correct radiotherapy/chemotherapy and to monitor the effectiveness of the therapetic strategy.     

Procoagulatory changes induced by head-up tilt test in patients with syncope: observational study

Background

Orthostatic hypercoagulability is proposed as a mechanism promoting cardiovascular and thromboembolic events after awakening and during prolonged orthostasis.We evaluated early changes in coagulation biomarkers induced by tilt testing among patients investigated for suspected syncope, aiming to test the hypothesis that orthostatic challenge evokes procoagulatory changes to a different degree according to diagnosis.

Methods

One-hundred-and-seventy-eight consecutive patients (age, 51 ± 21 years; 46% men) were analysed. Blood samples were collected during supine rest and after 3 min of 70° head-up tilt test (HUT) for determination of fibrinogen, von Willebrand factor antigen (VWF:Ag) and activity (VWF:GP1bA), factor VIII (FVIII:C), lupus anticoagulant (LA1), functional APC-resistance, and activated prothrombin time (APTT) with and without activated protein C (C+/?). Analyses were stratified according to age, sex and diagnosis.

Results

After 3 min in the upright position, VWF:Ag (1.28 ± 0.55 vs. 1.22 ± 0.54; p < 0.001) and fibrinogen (2.84 ± 0.60 vs. 2.75 ± 0.60, p < 0.001) increased, whereas APTT/C+/? (75.1 ± 18.8 vs. 84.3 ± 19.6 s; p < 0.001, and 30.8 ± 3.7 vs. 32.1 ± 3.8 s; p < 0.001, respectively) and APC-resistance (2.42 ± 0.43 vs. 2.60 ± 0.41, p < 0.001) decreased compared with supine values. Significant changes in fibrinogen were restricted to women (p < 0.001) who also had lower LA1 during HUT (p = 0.007), indicating increased coagulability. Diagnosis vasovagal syncope was associated with less increase in VWF:Ag during HUT compared to other diagnoses (0.01 ± 0.16 vs. 0.09 ± 0.17; p = 0.004).

Conclusions

Procoagulatory changes in haemostatic plasma components are observed early during orthostasis in patients with history of syncope, irrespective of syncope aetiology. These findings may contribute to the understanding of orthostatic hypercoagulability and chronobiology of cardiovascular disease.

     

Clinical review: Tuberculosis on the intensive care unit

Rates of tuberculosis (TB) are increasing in most west European nations. Patients with TB can be admitted to an ICU for a variety of reasons, including respiratory failure, multiorgan failure and decreased consciousness associated with central nervous system disease. TB is a treatable disease but the mortality for patients admitted with TB to an ICU remains high. Management challenges exist in establishing a prompt diagnosis and administering effective treatment on the ICU with potentially poor gastric absorption and high rates of organ dysfunction and drug toxicity. In this review reasons for ICU admission, methods of achieving a confident diagnosis through direct and inferred methods, anti-tuberculosis treatment (including steroid and other adjuvant therapies) and specific management problems with particular relevance to the intensivist are discussed. The role of therapeutic drug monitoring, judicious use of alternative regimes in the context of toxicity or organ dysfunction and when to suspect paradoxical tuberculosis reactions are also covered. Diagnostic and therapeutic algorithms are proposed to guide ICU doctors in the management of this sometimes complicated disease.     

Identification of Achromobacter xylosoxidans by detection of the bla(OXA-114-like) gene intrinsic in this species

Achromobacter xylosoxidans is an emerging pathogen among patients with cystic fibrosis. Here we describe a specific PCR for identification of this organism, based on detection of bla(OXA-114-like). Comparison of isolates by pulsed-field gel electrophoresis revealed evidence of cross-infection in some cases, but most patients harbored their own strain.     

Direct detection of Staphylococcus osteoarticular infections by use of Xpert MRSA/SA SSTI real-time PCR

We evaluated the Xpert MRSA/SA SSTI real-time PCR assay (Cepheid, Sunnyvale, CA) directly on perioperative bone and joint samples. The sensitivity and specificity for detection of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and methicillin-resistant coagulase-negative Staphylococcus were, respectively, 100% and 98.3%, 100% and 100%, and 100% and 95.3%. The median total test turnaround time was 72 min for PCR versus 79 h for culture. Using these rapid results, appropriate antibiotic treatment could be rapidly initiated.     

Photo- and thermal degradation of piroxicam in aqueous solution

Light and temperature have considerable effect on the degradation of piroxicam in aqueous solutions. The pH and acetate buffer ions also affect the degradation process. The apparent first-order rate constants for the photochemical and thermal degradation of piroxicam have been determined as 2.04-10.01 and 0.86-3.06×10(-3) min(-1), respectively. The first-order plots for the degradation of piroxicam showed good linearity within a range of 20-50% loss of piroxicam at pH 2.0-12.0. The rate-pH profile for the photodegradation of piroxicam is a U-shaped curve and for the thermal degradation a bell-shaped curve in the pH range of 2.0-12.0. The thermal degradation of piroxicam was maximum around pH 6.0. It is increased in the presence of acetate ions but was not affected by citrate and phosphate ions.     

Neoadjuvant chemotherapy for locally advanced breast cancer: a single center experience

Neoadjuvant chemotherapy (NAC) is one of the treatment options for patients with locally advanced breast cancer (LABC). Preoperative chemotherapy potentially may reduce the extent of the surgery and offers the opportunity to assess the chemosensitivity of the tumor in vivo. Herein, we evaluated the results of NAC in Turkish LABC patients. We retrospectively analyzed 73 LABC patients. Anthracycline/taxane-based chemotherapy regimens were administered. Patients were stratified according to age, menopausal status, type of surgery, response to the treatment, histopathological properties, and survival. After 3–6 cycles of chemotherapy, patients were re-staged radiologically and surgery was performed in operable patients. Adjuvant chemotherapy was administered as needed. The median age was 45 (29–93) at the time of diagnosis. Sixteen percentage of patients were younger than 35 years of age and 45.2% were premenopausal. Median follow-up time was 20.2 months. Sixty-seven out of 73 patients responded to therapy (89%). Breast conserving surgery was possible in the 15% of the patients. In histopathological analysis, lymph node invasion was detected in 85%. The estrogen (ER) and progesterone (PR) receptor were positive in 78.1% and c-erb-B2 was positive in 17.5% of patients. The median disease-free survival (DFS) was 44 months (SE: 9; %95 CI: 27.1–60.8), overall survival (OS) was not reached at the time of analysis. Three-year DFS and OS were 58% and 91.9%, respectively. In a multivariate Cox regression analyses; no demographic or pathologic prognostic parameter predicted overall survival. In recent years, NAC in breast cancer has become a viable treatment option for patients with LABC. NAC is not commonly applied in Turkey. The response rate to NAC in Turkish breast cancer patients is encouragingly high. Broader efforts should be made to evaluate breast cancer patients preoperatively at tumor boards for proper treatment sequence.