Elevated ARG1 expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients

Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their “M1/M2” activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p = 0 .032), moist desquamation (p = 0 .027), and CTC grade (p = 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p = 0 .069), moist desquamation (p = 0 .037), and CTC grade (p = 0 .046). To conclude, our findings underline for the first time the biological significance of increased ARG1 mRNA levels as an early independent predictive biomarker of RT-induced acute skin toxicities.     

What surgical approach has the lowest risk of the lower lid complications in the treatment of orbital floor and periorbital fractures? A frequentist network meta-analysis

Purpose

Evidence on the best surgical approach with the lowest lower lid complications (LLCs) in the treatment of orbital floor (OF) and periorbital fractures (POFs) is limited because of the absence of head-to-head studies. We performed this network meta-analysis (NMA) to compare various surgical approaches in treatment of OFs and POFs, with respect to LLCs.

Cefotaxime-heparin lock prophylaxis against hemodialysis catheter-related sepsis among Staphylococcus aureus nasal carriers

Staphylococcus aureus nasal carriers undergoing hemodialysis (HD) through tunneled cuffed catheters (TCCs) form a high-risk group for the development of catheter-related bloodstream infections (CRBSI) and ensuing morbidity. The efficacy of antibiotic-locks on the outcomes of TCCs among S. aureus nasal carriers has not been studied earlier. Persistent nasal carriage was defined by two or more positive cultures for methicillin-susceptible (MSSA) or methicillin-resistant (MRSA) S. aureus of five standardized nasal swabs taken from all the participants dialyzed at a large out-patient HD center affiliated to a tertiary care hospital. Of 218 participants, 82 S. aureus nasal carriers dialyzed through TCCs (n = 88) were identified through April 2005 to March 2006 and randomized to two groups. Group I comprised of 39 nasal carriers who had TCCs (n = 41) "locked" with cefotaxime/heparin while group II included 43 patients with TCCs (n = 47) filled with standard heparin. The CRBSI incidence and TCC survival at 365 days were statistically compared between the two groups. A significantly lower CRBSI incidence (1.47 vs. 3.44/1000 catheter-days, P <0.001) and higher infection-free TCC survival rates at 365 days (80.5 vs. 40.4%, P <0.0001) were observed in the cefotaxime group compared with the standard heparin group. However, no significant difference in MRSA-associated CRBSI incidence was observed between the two groups. Cefotaxime-heparin "locks" effectively reduced CRBSI-incidence associated with gram-positive cocci, including MSSA, among S. aureus nasal carriers. There remains a compelling requirement for antibiotic-locks effective against MRSA.     

Giant substernal goiter with chylothorax

A 60-year-old woman presented with a huge goiter extending from the lower jaw to the diaphragm. Right pleurocentesis produced chylous fluid. A cervicothoracic incision was used to totally excise the substernal goiter, with near-total excision of the cervical goiter, and repair of the lymphatic leakage.     

Mechanical characteristics of the bone-graft-cement interface after impaction allografting.

Impaction allografting is an attractive procedure for the treatment of failed total hip replacements. The graft-cement-host bone interface after impaction allografting has not been characterized, although it is a potential site of subsidence for this type of revision total hip reconstruction. In six human cadaveric femurs, the cancellous bone was removed proximally and local diaphyseal lytic defects were simulated. After the impaction grafting procedure, the specimens were sectioned in 6 mm transverse sections and push-out tests were performed. From the adjacent sections the percentage cement contact of the PMMA cement with the endosteal bone surface was determined. The host bone interface mechanical properties varied significantly along the femur largely due to different interface morphologies. The apparent host bone interface shear strength was highest around the lesser trochanter and lowest around the tip of the stem. A significant positive correlation was found between the percentage cement contact and the apparent host bone interface shear strength (r2 = 0.52). The sections failed in 69% of the cases through a pure host bone interface failure without cement or allograft failure, 19% failed with local cement failure, and 12% with a local allograft failure. The apparent host bone interface strength was on average 89% lower than values reported for primary total hip replacements and were similar to cemented revisions proximally and lower distally. This study showed that cement penetration to the endosteal surface enhanced the host bone-graft interface.     

Role and Operative Risk of Bilateral Adrenalectomy in Hypercortisolism

n = 78), ectopic ACTH syndrome ( n = 3), and primary adrenocortical nodular dysplasia (Carney-Meador syndrome) ( n = 1). Before operation 37% of the patients had severe symptoms of hypercortisolism. A bilateral posterior approach was undertaken in 58 patients, whereas 18 patients had an anterior transabdominal approach and 6 patients a laparoscopic approach. There were two operative deaths (2.4%). Postoperative complications occurred mostly in cases of advanced disease and were observed in 14 patients (17%), among whom 4 had severe complications. At long-term follow-up, one recurrence of hypercortisolism and 12 Nelson syndromes (15%) were observed. In conclusion, bilateral adrenalectomy carries an acceptable operative risk, and we recommend bilateral adrenalectomy rather than long-term suppressive therapy in patients requiring prompt and definitive control of their hypercortisolism or after pituitary surgery failure.