Protease inhibitor monotherapy is associated with a higher level of monocyte activation,bacterial translocation and inflammation

Introduction

Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation.

Methods

We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed.

Results

CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16−CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16−CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01).

Conclusions

Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed.     

Design Method of a Foldable Ventricular Assist Device for Minimally Invasive Implantation

To date, ventricular assist devices (VADs) have become accepted as a therapeutic solution for end‐stage heart failure patients when a donor heart is not available. Newer generation VADs allow for a significant reduction in size and an improvement in reliability. However, the invasive implantation still limits this technology to critically ill patients. Recently, expandable/deployable devices have been investigated as a potential solution for minimally invasive insertion. Such a device can be inserted percutaneously via peripheral vessels in a collapsed form and operated in an expanded form at the desired location. A common structure of such foldable pumps comprises a memory alloy skeleton covered by flexible polyurethane material. The material properties allow elastic deformation to achieve the folded position and withstand the hydrodynamic forces during operation; however, determining the optimal geometry for such a structure is a complex challenge. The numerical finite element method (FEM) is widely used and provides accurate structural analysis, but computation time is considerably high during the initial design stage where various geometries need to be examined. This article details a simplified two‐dimensional analytical method to estimate the mechanical stress and deformation of memory alloy skeletons. The method was applied in design examples including two popular types of blade skeletons of a foldable VAD. Furthermore, three force distributions were simulated to evaluate the strength of the structures under different loading conditions experienced during pump operation. The results were verified with FEM simulations. The proposed two‐dimensional method gives a close stress and deformation estimation compared with three‐dimensional FEM simulations. The results confirm the feasibility of such a simplified analytical approach to reveal priorities for structural optimization before time‐consuming FEM simulations, providing an effective tool in the initial structural design stage of foldable minimally invasive VADs.     

The impact of the prevention strategies on the indirect effects of CMV infection in solid organ transplant recipients

Transplant recipients receiving immunosuppressive therapy are at increased risk of active cytomegalovirus (CMV) infection and disease. Without appropriate prophylaxis, as many as 80% of solid organ transplant recipients may experience CMV infection. In addition to the direct effects of CMV, infection may be associated with a range of indirect effects, including an increase in risk of other infections, as well as a higher incidence of rejection, graft loss and death. The indirect effects of CMV infection can vary depending on the transplanted organ. For example, CMV-infected kidney transplant recipients may be at increased risk of cardiovascular disease and diabetes, while CMV infection in liver transplant recipients may potentiate hepatitis C infection and increase the risk of post-transplant lymphoproliferative disease. Indirect effects result from a number of pathological processes, including immune modulation and immunosuppression, generation of cytotoxic, pro-inflammatory responses, and smooth muscle proliferation. Prophylactic treatment with antiviral medication can reduce the risk of CMV disease, thereby improving graft survival and overall outcomes, particularly in kidney and heart transplant recipients. Antiviral prophylaxis should be considered for all patients at risk of CMV infection after solid organ transplantation. In this paper we review the main indirect effects of CMV infection in solid organ transplant recipients, and the impact of CMV prophylaxis on these effects.     

Malar fat pad suspension through intraoral approach: a personal technique

Background

For decades, facelifting has been the gold standard for facial rejuvenation. However, there is a current tendency towards new and less complex procedures. The reposition of the malar fat pad plays a central role to restore a convex mid-face contour, and until now, it has been achieved mainly through large incisions or endoscopic techniques.

Methods

Authors present a minimum scar procedure using a 20-cm needle: a 45-min operation that lifts the ptotic malar fat to restore a youthful looking facialvolume. Nineteen consecutive patients were addressed using this technique with consistent satisfactory results between the years 2007 and 2012.

Results

Patients were mostly women (16), between 24 and 70 years of age. Six patients had this procedure as a single surgery, the rest in combination with other aesthetic procedures. All of them were satisfied with results at one year after the procedure operation.

Conclusions

The authors conclude that this is a reliable procedure that obtains the desired results in mid-face rejuvenation by restoring a youthful contour, avoiding large visible incisions.

Level of evidence: Level IV, therapeutic study

     

“Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury”

Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser—780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n?=?3), control surgery (n?=?3), laser 6 h after surgery (n?=?5), laser 48 h after surgery (n?=?5), medullar lesion (n?=?5) without phototherapy, medullar lesion?+?laser 6 h after surgery (n?=?5), and medullar lesion?+?laser 48 h after surgery (n?=?5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.     

Lymphoepithelial cysts and cystic lymphangiomas: Underrecognized benign cystic lesions of the pancreas

AIM: To identify their diagnostic and prognostic clinical characteristics in a large series.METHODS: Retrospective review of clinicopathologic and imaging characteristics of patients diagnosed with lymphoepithelial cysts and cystic lymphangiomas of the pancreas at Massachusetts General Hospital.RESULTS: Twelve patients were identified between 1/1/1997 and 8/1/2007. Their median age was 55.5 years(range 19-78 years), and 6 were females. The le-sion was incidentally discovered in half of the patients.Contrast enhanced computed tomography demonstrat-ed that the cysts had thin walls, without calcifications, pancreatic duct dilation or pancreatic parenchyma inva-sion. Endoscopic ultrasound with fine needle aspiration(EUS/FNA) confirmed the diagnosis of a lymphoepithe-lial cyst in 3 patients, one of whom was spared an op-eration and continues to do well after 6 years. Eleven patients had a resection: 3 pancreaticoduodenecto-mies, 7 distal pancreatectomies, and 1 enucleation. The median size of the cysts was 3 cm(range 2-20 cm). At a median follow-up of 57 mo no recurrences or other pancreas-related conditions occurred.CONCLUSION: Lymphoepithelial cysts and cystic lymphangiomas of the pancreas can be diagnosed with a combination of contrast-enhanced computed tomog-raphy scans and EUS/FNA. If the lesion is asymptom-atic, an operation might be avoided.     

Prospective randomized study comparing everolimus and mycophenolate sodium in de novo kidney transplant recipients from expanded criteria deceased donor

The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single‐center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r‐ATG/EVR, n = 88), or mycophenolate (r‐ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy‐proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06–0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r‐ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r‐ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).     

Proton magnetic resonance spectroscopy of brain-stem lesions

The imaging findings of brain-stem lesions are often nonspecific and histological diagnosis is limited because of fear of complications associated with biopsy. A noninvasive method for tissue characterization is therefore highly desirable. We undertook a review of proton magnetic resonance spectroscopy (MRS) of patients with solitary brain-stem lesions to determine if MRS could characterize them. We carried out single- or multivoxel proton MRS using long echo times (135 or 270 ms) on 34 patients with solitary brain-stem lesions. We analyzed the following peaks: choline (Cho), creatine (Cr), N-acetylaspartate (NAA), and lipids/lactate (Lip) and calculated peak height ratios for Cho/Cr, NAA/Cr and Lip/Cr. The results were compared with histology in nine patients and with the presumptive diagnosis in 25. We also performed single-voxel proton MRS on the brain stem of five normal volunteers. There were differences in all ratios between controls and the patients with neoplastic and non-neoplastic lesions: Cho/Cr was low in non-neoplastic and high in neoplastic lesions (control: 1.8+/-0.1; non-neoplastic: 1.4+/-0.2; neoplastic: 2.0+/-0.2); NAA/Cr was low in non-neoplastic, and lower in neoplastic lesions (control: 2.3+/-0.1; non-neoplastic: 1.4+/-0.2; neoplastic: 1.2+/-0.1), and Lip/Cr was elevated in both neoplastic and non-neoplastic lesions (control: 0.04+/-0.02; nonneoplastic: 1.9+/-0.7; neoplastic:1.9+/-0.7).