Lauri Ahvenjärvi

Safety and biodistribution study of bone marrow–derived mesenchymal stromal cells and mononuclear cells and the impact of the administration route in an intact porcine model

BACKGROUND AIMS Bone marrow mononuclear cells (BM-MNCs) and bone marrow-derived mesenchymal stem stromal cells (BM-MSCs) could have therapeutic potential for numerous conditions, including ischemia-related injury. Cells transplanted intravascularly may become entrapped in the lungs, which potentially decreases their therapeutic effect and increases the risk for embolism. METHODS Twelve pigs were divided into groups of 3 and received (99m)Tc- hydroxymethyl-propylene-amine-oxime-labeled autologous BM-MNCs or allogeneic BM-MSCs by either intravenous (IV) or intra-arterial (IA) transplantation. A whole body scan and single photon emission computed tomography/computed tomography (SPECT/CT) were performed 8 h later, and tissue biopsies were collected for gamma counting. A helical CT scan was also performed on 4 pigs to detect possible pulmonary embolism, 2 after IV BM-MSC injection and 2 after saline injection. RESULTS The transplantation route had a greater impact on the biodistribution of the BM-MSCs than the BM-MNCs. The BM-MNCs accumulated in the spleen and bones, irrespective of the administration route. The BM-MSCs had relatively higher uptake in the kidneys. The IA transplantation decreased the deposition of BM-MSCs in the lungs and increased uptake in other organs, especially in the liver. Lung atelectases were frequent due to mechanical ventilation and attracted transplanted cells. CT did not reveal any pulmonary embolism. CONCLUSIONS Both administration routes were found to be safe, but iatrogenic atelectasis might be an issue when cells accumulate in the lungs. The IA administration is effective in avoiding pulmonary entrapment of BM-MSCs. The cell type and administration method both have a major impact on the acute homing.

Diagnostic accuracy of computed tomography imaging of surgically treated acute acalculous cholecystitis in critically ill patients.

BACKGROUND Acute acalculous cholecystitis (AAC) is a potentially fatal condition mainly affecting critically ill patients. Current experience from computed tomography (CT) findings in AAC is contradictory. METHODS CT images of 127 mixed medical-surgical intensive care unit patients were retrospectively reviewed for the following findings: bile density, thickness and enhancement of the gallbladder (GB) wall, subserosal edema, greatest perpendicular diameters of the GB, width of extrahepatic bile ducts, gas within the GB, ascites, peritoneal fat edema, and diffuse tissue edema. Forty-three of these patients underwent open cholecystectomy, and 8 patients revealed a normal GB, 26 an edematous GB, and 9 a necrotic AAC. RESULTS Abnormal CT findings were present in 96% of all the intensive care unit patients. Higher bile density in the GB body and subserosal edema was associated with an edematous GB (specificity, 93.6%; sensitivity, 23.1%). The most specific findings predicting necrotic AAC were gas in the GB wall or lumen, lack of GB wall enhancement, and edema around the GB (specificity, 99.2%, 94.9%, and 92.4%, respectively; and sensitivity, 11.1%, 37.5%, and 22.2%, respectively). CONCLUSIONS The frequency of nonspecific abnormal findings in the GB of critically ill patients limits the diagnostic value of CT scanning in detecting AAC. However, in the case of totally normal GB findings in CT, the probability of necrotic AAC is low.

The occurrence of pneumonia diagnosis among neurosurgical patients: the definition matters.

BackgroundDiagnosis of pneumonia in the hospital setting is a challenge due to the absence of a generally accepted pneumonia definition.MethodsWe prospectively evaluated six different clinical criteria for diagnosing pneumonia—physician’s diagnosis (A), was compared to common methods, i.e., general surveillance method (B), consensus clinical criteria (C), and other three criteria (D, E, and F) among 390 neurosurgical patients treated in either the intensive care unit or the neurosurgical ward in a university hospital.ResultsThe frequencies of pneumonia cases were: group A, 66 (16.9%); group B, 41 (10.1%); and group C, 55 (14.1%). Only 28 pneumonia cases were identified by all three criteria. The kappa values were: between A and B, 0.42 (95% confidence interval, CI; 0.27–0.57); between A and C, 0.49 (95% CI; 0.35–0.63); and between B and C, 0.68 (95% CI; 0.55–0.80). In group A, there were 34 false positive cases according to criterion B and 25 according to criterion C. Pneumonia cases were identified according to criterion D in 13 (3.3%), E in 35 (9.0%), and F in 51 (13.1%) cases, respectively.ConclusionsThere was great variability in the presence of pneumonia among neurosurgical patients, depending on the criteria used. Our results support the idea that a more exact method for pneumonia diagnosis should be implemented to obtain more reliable results in this important infection of hospitalized patients, which is also used for benchmarking purposes. Furthermore, it seems important to treat all clinically suspected pneumonia cases whether or not the surveillance criteria are fulfilled.

Multi-detector computed tomography in critically ill patients

Background: There is a lack of studies showing the overall impact of multi‐detector computed tomography (MDCT) on the treatment of critically ill patients in a general intensive care unit (ICU) setting.

Early chest computed tomography in adult acute severe community‐acquired pneumonia patients treated in the intensive care unit

The value of early chest computed tomography (CT) was evaluated among severe community‐acquired pneumonia (SCAP) patients.

Attempt to treat congenital pseudarthrosis of the tibia with mesenchymal stromal cell transplantation

BACKGROUND AIMS Congenital pseudarthrosis of the tibia (CPT) caused by neurofibromatosis type 1 (NF1) is a refractory disease occurring in childhood. We present two cases that had failed all earlier treatment attempts and, as a last treatment attempt, the patients were chosen to receive mesenchymal stromal cell (MSC) transplantation prior to amputation. METHODS The MSC from bone marrow (BM) were harvested from the iliac crest and cultured in osteoinductive medium for 3 weeks. The cultured MSC were injected in solution into BM canals of the tibia and around the resection line or bone defect in a 3-dimensional collagen sponge scaffold. After the MSC transplantation, the patients were monitored during a 10-month follow-up period. In both cases, bone formation at the pseudarthrosis site was observed and two of three treated bone defects healed. For clinical reasons not related to cell transplantation, such as new infection and pseudarthrosis and severe shortening of the leg, both extremities were finally amputated and bone samples were analyzed to evaluate MSC therapy effect and safety. RESULTS MSC transplantation normalized bone remodeling, promoted bone resorption and improved the overall structure of bone. The number of osteoclasts in the cortical bone was 2-fold higher compared with the monitored situation before MSC transfer. In addition, the mineral content of the bone improved after transplantation. We could see no sign of aberrant bone formation or malignant transformation. CONCLUSIONS Our data suggest that MSC transplantation is a possibility for treatment of CPT caused by NF1 in less severe cases without adjunct defects.