Population Pharmacokinetics and Target Attainment of Meropenem in Plasma and Tissue of Morbidly Obese Patients after Laparoscopic Intraperitoneal Surgery.

Meropenem serves as a clinically important, broad-spectrum antibiotic. While meropenem is commonly used in obese patients, its pharmacokinetics in this patient group is not well known. Our aim was to characterize the population pharmacokinetics and target attainment in plasma, subcutaneous tissue, and peritoneal fluid for meropenem in morbidly obese patients. Four doses of 1g meropenem were given as 15-min infusions every 8 h to five morbidly obese patients (body mass index [BMI], 47.6 to 62.3 kg/m(2)). After the fourth dose, serial meropenem concentrations were determined in plasma and, via microdialysis, in subcutaneous tissue and peritoneal fluid. All concentrations were analyzed simultaneously via population modeling, and target attainment probabilities predicted via Monte Carlo simulations using the target of unbound meropenem concentrations above the MIC for at least 40% of the dosing interval. For patients with 53 kg fat-free mass, total clearance was 18.7 liters/h and volume of distribution at steady state was 27.6 liters. The concentrations in subcutaneous tissue and peritoneal fluid largely paralleled those in plasma (equilibration half-life, <30 min). The area under the curve (AUC) in subcutaneous tissue divided by the plasma AUC had a mean of 0.721. For peritoneal fluid, this AUC ratio had a mean of 0.943. Target attainment probabilities were >90% after 1 g meropenem every 8 h as a 15-min infusion for MICs of up to 2 mg/liter in plasma and peritoneal fluid and 0.5 mg/liter in subcutaneous tissue. Meropenem pharmacokinetics in plasma and peritoneal fluid of obese patients was predictable, but subcutaneous tissue penetration varied greatly. (This study has been registered at ClinicalTrials.gov under registration no. NCT01407965.).

Laparoscopic intraperitoneal mesh fixation with fibrin sealant of a Spigelian hernia.

Spigelian hernia is a rare clinical entity and has a subtle clinical presentation with vague abdominal pain, which can cause an important delay in diagnosis. Given the relatively high risk of incarceration the diagnosis of Spigelian hernia is an indication for surgical repair. Laparoscopic Spigelian mesh herniorraphy has gained recognition as an effective tension-free method and is associated with lower recurrence. Appropriate fixation techniques are however required to reduce complications such as nerve irritation, hematoma, and postoperative chronic pain. In this case report we describe a novel approach in laparoscopic mesh repair of Spigelian hernia, securing a lightweight composite mesh with fibrin sealant. This fixation seems to be a reasonable, feasible alternative to the standard tissue-penetrating mesh fixation.

Minimal access kidney transplant: a novel technique to reduce surgical tissue trauma.

OBJECTIVES: Minimally invasive surgery and minimal access surgery has replaced conventional surgical procedures during the last 15 years with benefits including a decrease in postoperative pain, time spent convalescing, early return to normal activities, and pleasing cosmetic results. Many centers perform kidney transplant through an oblique or J-shaped approach deep into the iliac fossa. Both approaches have possible disadvantages regarding the extent of tissue trauma. Therefore, we introduced a new minimal access kidney transplant technique in our kidney transplant program in 2008 and report the outcomes of the first 10 patients transplanted with this technique. MATERIALS AND METHODS: Between November 2008 to May 2009, ten kidney recipients were subjected to the minimal access kidney transplant technique. These patients represent a consecutive series of kidney transplants performed by the senior surgeon or under the supervision of the senior surgeon of transplant surgery. RESULTS: The mean (± SD) age of the recipients was 47 ± 14.7 years (range, 28-67 y), the body mass index was 25 ± 2.02 (range, 23-30), the time of procedure was 126.2 ± 27.5 minutes (range, 90-165 min) with a mean (± SD) anastomoses time of 27.7 ± 8.4 minutes (range, 19-45 min). Follow-up for all recipients was at least 18 months. There was no reintervention necessary, no wound infections, no primary nonfunction or a delayed graft function, no need for dialysis, no acute rejection episodes, no graft loss, no wound dehiscence, no incisional hernia, or lymphocele. Furthermore, no urologic complications or vascular complications were observed. CONCLUSIONS: Our reported technique was used on heart-beating donor kidneys as well as on living-donor organs and is safe with less comorbidity. This minimal access kidney transplant technique might be an alternative procedure for avoiding some of the disadvantages of conventional approaches used for kidney transplant.

Laparoscopic splenectomy of a wandering spleen with coincidental enormous splenomegaly.

Ectopy of the spleen also referred to as wandering spleen is a rare condition and preferentially treated by laparoscopic splenopexy. However, in complicated cases with torsion and consecutive infarction of the spleen splenectomy is required. Performing the splenectomy of a wandering spleen laparoscopically has already been reported as a save therapeutic option. However, open splenectomy is usually preferred in case of massive splenomegaly for both, wandering and regular localized spleen. In this case report we describe a laparoscopic technique as alternative for conventional splenectomy in the case of a huge wandering spleen.

The role of the casein kinase 1 (CK1) family in different signaling pathways linked to cancer development.

The members of the casein kinase 1 (CK1) family are highly conserved and are expressed in many eukaryotes ranging from yeast to humans. Mammalian CK1 isoforms (alpha, beta, gamma, delta, epsilon) and their splice variants are involved in diverse cellular processes including membrane trafficking, circadian rhythm, cell cycle progression, chromosome segregation, apoptosis and cellular differentiation. Mutations and deregulation of CK1 expression and activity has been linked to various diseases including neurodegenerative disorders such as Alzheimer's and Parkinson's disease, sleeping disorders and proliferative diseases such as cancer. In this review, we summarize the functions of CK1 and outline the participation of CK1 in signal transduction pathways linked to cancer development.