Extracorporeal photochemotherapy: a treatment for organ graft rejection.

Extracorporeal photochemotherapy (ECPC) has been investigated experimentally and in clinical conditions in transplant rejection treatment and prevention. Repeated injections of photochemically modified syngeneic alloreactive T cells prior to transplant significantly delay rejection in a mouse skin graft model as well as in a heterotopic heart transplant model in rats. In the latter, we found this effect to be dependent on 3 main parameters, i.e., treatment intensity (number of injections), schedule (injections before and after transplant), and associated immunosuppression (because there is no detectable effect in animals without immunosuppression). In human beings, ECPC was first used for the treatment of acute rejection episode after heart transplantation. At least 2 studies provided evidence that ECPC is as effective as high dose corticosteroids in controlling moderate acute rejections, and several case reports showed that ECPC could be effective in recurrent and/or steroid resistant rejections. ECPC has also been investigated in an open trial to prevent rejection episodes after heart transplantation in patients at high risk of acute rejection because of human leukocyte antigen (HLA) immunization and/or a second or third transplant and found to be successful. In heart transplant recipients at standard risk of rejection episodes, a small scale randomized trial showed a reduction in both rejection episodes and infections in the ECPC treated vs. the standard group. Beyond these studies and other isolated case reports, several large scale randomized trials in heart, lung, and even kidney transplantations (some of them already ongoing), will enable us to define the role of ECPC in the management of transplant recipients.     

Aerosol therapy in intensive and intermediate care units: prospective observation of 2808 critically ill patients

Purpose

Unlike in the outpatient setting, delivery of aerosols to critically ill patients may be considered complex, particularly in ventilated patients, and benefits remain to be proven. Many factors influence aerosol delivery and recommendations exist, but little is known about knowledge translation into clinical practice.

Methods

Two-week cross-sectional study to assess the prevalence of aerosol therapy in 81 intensive and intermediate care units in 22 countries. All aerosols delivered to patients breathing spontaneously, ventilated invasively or noninvasively (NIV) were recorded, and drugs, devices, ventilator settings, circuit set-up, humidification and side effects were noted.

Results

A total of 9714 aerosols were administered to 678 of the 2808 admitted patients (24 %, CI₉₅ 22–26 %), whereas only 271 patients (10 %) were taking inhaled medication before admission. There were large variations among centers, from 0 to 57 %. Among intubated patients 22 % (n = 262) received aerosols, and 50 % (n = 149) of patients undergoing NIV, predominantly (75 %) inbetween NIV sessions. Bronchodilators (n = 7960) and corticosteroids (n = 1233) were the most frequently delivered drugs (88 % overall), predominantly but not exclusively (49 %) administered to patients with chronic airway disease. An anti-infectious drug was aerosolized 509 times (5 % of all aerosols) for nosocomial infections. Jet-nebulizers were the most frequently used device (56 %), followed by metered dose inhalers (23 %). Only 106 (<1 %) mild side effects were observed, despite frequent suboptimal set-ups such as an external gas supply of jet nebulizers for intubated patients.

Conclusions

Aerosol therapy concerns every fourth critically ill patient and one-fifth of ventilated patients.

     

The independent association of massive blood loss with mortality in cardiac surgery

BACKGROUND: Although the association between massive perioperative blood loss (MBL) and adverse outcomes is well recognized, it is unclear whether MBL is an independent risk factor or, instead, simply a marker for other adverse events or severity of illness. The objective of this cohort study was to quantify the independent association of MBL in cardiac surgery with all-cause in-hospital mortality. STUDY DESIGN AND METHODS: Data were prospectively collected on consecutive patients who underwent cardiac surgery with cardiopulmonary bypass at a quaternary-care academic center from 1999 to 2003. The number of red blood cell (RBC) units transfused within 1 day of surgery was used as a surrogate measure of perioperative blood loss. Receiver-operating characteristic curve analyses were employed to identify the most appropriate cutoff for defining MBL. The independent association of MBL with mortality was determined with multivariable logistic regression analyses. Bootstrapping and sensitivity analyses were used to confirm the validity of the results. RESULTS: MBL was defined as receiving at least 5 units of RBCs within 1 day of surgery. Of 9215 patients analyzed, 1.8 percent (n = 169) died and 9.7 percent (n = 890) had MBL. After adjusting for multiple potential confounders (including perioperative adverse events), MBL was associated with an 8.1-fold (95% confidence interval, 3.9-17.0) increase in the odds of death. This risk estimate was stable across different modeling conditions as well as in bootstrap sampling. CONCLUSION: MBL after cardiac surgery has a strong, independent association with in-hospital mortality.     

Hypercalcemia induced by parathyroid hormone-related peptide after treatment of carcinoma

Squamous cell carcinoma of the head and neck is a rare cause of humoral hypercalcemia of malignancy. This paraneoplastic syndrome is usually one of the presenting symptoms of the disease. We report a case of squamous cell carcinoma of the oral cavity that presumably elaborated parathyroid hormone-related peptide (PTH-rP) and caused hypercalcemia only after radiotherapy and chemotherapy.     

Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation

Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3⁺CD19⁺ cell depletion (CD3/19D) versus CD34⁺ selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios^? FoxP3⁺Treg reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.     

Lasers for tattoo removal: a review

Tattoos have existed and have been used as an expression of art by man for ages—and so have the techniques to remove them. Lasers based on the principle of selective photothermolysis are now being used to remove black as well as colorful tattoos with varying successes. The commonly used lasers for tattoo removal are the Q-switched 694-nm ruby laser, the Q-switched 755-nm alexandrite laser, the 1,064-nm Nd:YAG laser, and the 532-nm Nd:YAG laser. Newer techniques and methods are evolving in tattoo removal with lasers. Choosing the right laser for the right tattoo color is necessary for a successful outcome. Our review aims to understand the principles of laser tattoo removal and their applications for different types and colors of tattoos. The review also highlights the complications that can occur such as dyspigmentation, allergic reactions, epidermal debris, ink darkening, and so on, in this process and how to prevent them.     

Neodymium:yttrium-aluminium-garnet laser for excision of pulmonary nodules: an institutional review

Eighty patients amongst 850 undergoing pulmonary surgery with the use of neodymium:yttrium-aluminium-garnet (Nd:YAG) laser had a solitary pulmonary nodule (≤ 50 mm) on chest radiography, which was confirmed or suspected pre-operatively to be primary lung cancer. All patients had a mini-thoracotomy to expose the lesion. They then had Nd:YAG laser to excise the nodule locally. There was no hospital mortality. Six patients had non-fatal post-operative complications. Pathologically, 46 patients had primary lung cancer and ten had secondary lung cancer. Twenty-four others had benign lesions. Mean hospital stay was 5.5 days. Post-operative reduction of forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁) was 14% and 13% (mean), respectively. Thirty-seven patients with primary lung cancer were followed up for between 12 months and 60 months. Mean survival time of these patients was 39 months (s.d. 13 months). It was concluded that Nd:YAG laser for pulmonary nodular lesions should be considered for a selected group of patients unsuitable for standard resection.     

The pharmacokinetic profile of recombinant human erythropoietin is unchanged in patients undergoing cardiac surgery

Background

In anticipation of future studies, we examined the pharmacokinetics profile of erythropoietin (EPO) in patients undergoing cardiac surgery.

Methods

Cardiac surgical patients were enrolled into one of six groups: four cardiopulmonary bypass (CPB) groups [placebo (n?=?6), 250 IU/kg EPO (n?=?3), 500 IU/kg EPO (n =?3), and 500 IU/kg EPO, two doses (n =?6)] and two off-pump coronary artery bypass (OPCAB) groups [placebo (n?=?3) and 500 IU/kg EPO (n?=?3)]. The EPO was administered prior to anesthesia and 10 min after CPB (if required). Blood samples for serum EPO were collected at baseline, 10 min after dosing, 5 min after sternotomy, during CPB or the equivalent for OPCAB (5, 15, 45, 60 min), and post-CPB (5, 15, 45, and 60 min, 6, 12 and 24 h, and daily until day 5).

Results

Endogenous EPO increased within 24 h of surgery in the placebo group and remained elevated. There was approximately a 40% decrease in serum EPO concentration at the initiation of CPB due to an increase in circulatory blood volume. There were no differences in apparent volume of distribution in the plasma (Vc) (42.2?±?9.9, 39.8?±?6.3, 42.3?±?14.0 mL/kg), clearance (CL) (4.63?±?1.14, 3.44?±?0.68, 4.27?±?0.52 mL h/kg), and t_½ (16.4?±?8.0 16.9?±?10.6, 22.4?±?9.3 h) between the CPB treatment groups. The pharmacokinetic profile of EPO in the OPCAB group was similar to that for the CPB groups: Vc = 39.3?±?7.0 mL/kg, CL = 4.98?±?0.17 mL h/kg and t_½ = 17.1?±?18.1 h.

Conclusions

CPB had no apparent effect on the pharmacokinetics of EPO.