Effect of albumin substitution on pharmacokinetics of piperacillin/tazobactam in patients with severe burn injury admitted to the ICU.

BACKGROUND: Pathophysiological changes in severely burned patients alter the pharmacokinetics (PK) of anti-infective agents, potentially leading to subtherapeutic concentrations at the target site. Albumin supplementation, to support fluid resuscitation, may affect pharmacokinetic properties by binding drugs. This study aimed to investigate the PK of piperacillin/tazobactam in burn patients admitted to the ICU before and after albumin substitution as total and unbound concentrations in plasma. PATIENTS AND METHODS: Patients admitted to the ICU and scheduled for 4.5 g piperacillin/tazobactam administration and 200 mL of 20% albumin substitution as part of clinical routine were included. Patients underwent IV microdialysis, and simultaneous arterial plasma sampling, at baseline and multiple timepoints after drug administration. PK analysis of total and unbound drug concentrations under steady-state conditions was performed before and after albumin supplementation. RESULTS: A total of seven patients with second- to third-degree burns involving 20%-60% of the total body surface were enrolled. Mean (SD) AUC0-8 (h·mg/L) of total piperacillin/tazobactam before and after albumin substitution were 402.1 (242)/53.2 (27) and 521.8 (363)/59.7 (32), respectively. Unbound mean AUC0-8 before and after albumin supplementation were 398.9 (204)/54.5 (25) and 456.4 (439)/64.5 (82), respectively. CONCLUSIONS: Albumin supplementation had little impact on the PK of piperacillin/tazobactam. After albumin supplementation, there was a numerical increase in mean AUC0-8 of total and unbound piperacillin/tazobactam, whereas similar Cmax values were observed. Future studies may investigate the effect of albumin supplementation on drugs with a higher plasma protein binding.

A new nomogram to predict the need for tracheostomy in burned patients.

PURPOSE: To evaluate the impact of tracheostomy on complications, dysphagia and outcome in second and third degree burned patients. METHODS: Inpatient mortality, dysphagia, severity of burn injury (ABSI, TBSA) and complications in tracheotomized burn patients were compared to (I) non-tracheotomized burn patients and (II) matched tracheotomized non-burn patients. RESULTS: 134 (30.9%) out of 433 patients who underwent tracheostomy, had a significantly higher percentage of inhalation injury (26.1% vs. 7.0%; p < 0.001), higher ABSI (8.9 ± 2.1 vs. 6.0 ± 2.7; p < 0.001) and TBSA score (41.4 ± 19.7% vs. 18.6 ± 18.8%; p < 0.001) compared to 299 non-tracheotomized burn patients. However, complications occurred equally in tracheotomized burn patients and matched controls and tracheostomy was neither linked to dysphagia nor to inpatient mortality at multivariate analysis. In particular, dysphagia occurred in 6.2% of cases and was significantly linked to length of ICU stay (OR 6.2; p = 0.021), preexisting neurocognitive impairments (OR 5.2; p = 0.001) and patients' age (OR 3.4; p = 0.046). A nomogram was calculated based on age, TBSA and inhalation injury predicting the need for a tracheostomy in severely burned patients. CONCLUSION: Using the new nomogram we were able to predict with significantly higher accuracy the need for tracheostomy in severely burned patients. Moreover, tracheostomy is safe and is not associated with higher incidenc of complications, dysphagia or worse outcome.

Computed tomography accelerates staging in patients with Merkel cell carcinoma.

PURPOSE: No imaging algorithms for diagnostic imaging in patients suffering from Merkel cell carcinoma (MCC) have been established so far and thus staging work-up is challenging. Long presentation-to-treatment intervals determine further treatment course and, consequently, have an impact on clinical outcome in patients with MCC. METHODS: In this retrospective study, diagnostic imaging of 37 MCC patients was analyzed. CT, ultrasound, and PET/PET-CT imaging for primary staging work-up with time frames from patients´ initial presentation and imaging until completion of tumor staging were analyzed. RESULTS: Tumor staging could be completed earlier when (1) less examinations (35 vs. 42 days) were carried out or (2) computed tomography was used as the initial imaging modality (28 vs. 35 days). Furthermore, CT imaging, when used as the initial imaging study, was linked to less follow-up imaging (3 vs. 6). CONCLUSION: Computed tomography as the first-staging imaging technique in MCC patients leads to less follow-up studies and fastest completion of tumor staging.

Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease.

BACKGROUND: The purpose of this study was to determine whether the expression of 15-lipoxygenase-1 (ALOX15) in primary tumour specimens predicts lymph node metastasis and subsequently clinical outcome in Merkel cell carcinoma (MCC) patients. METHODS: A retrospective medical chart review of 33 patients was performed between 1994 and 2014. Eleven out of 33 (33%) Patients with primary MCC stages I and II were categorised as group I. Twenty two out of 33 (67%) Patients with regional lymph node metastases and/or distant metastases were defined as group II. All available tumour samples were immunostained for ALOX15, Podoplanin and MCPyV large T-protein antibody. RESULTS: ALOX15 expression was observed in 19/23 (83%) primary tumour samples and in all lymph node metastasis. Primary tumours in patients with stage III and IV disease showed a higher expression rate of ALOX15 compared to patients with early stage disease (11/12 (92%) and 8/11 (73%), respectively). In group I, five patients (45%) were MCPyV positive, whereas in group II, 15 patients (68%) were MCPyV positive. The median lymphatic vessel density in ALOX15 negative group I primary tumour samples was lower compared to the median lymphatic vessel density in ALOX15 positive group I primary tumour probes (2.7 range, 1-4.3 vs 4.7 range, 4.0-7.3). Furthermore, all 17 samples of MCC metastases showed ALOX15 expression with a median lymphatic vessel density (not lymph node metastases) of 5.3 (range 2.0-7.3). CONCLUSION: In the current study, we were able to show ALOX15 expression in the primary MCC sample and the metastasis sample. Based on the findings of the current study, expression rate of ALOX15 in primary MCC and metastases is possibly linked to an increased lymphatic vessel density.

Phrenic Nerve Transfer to Musculocutaneous Nerve: An Anatomical and Histological Study.

BACKGROUND: To restore elbow flexor muscle function in case of traumatic brachial plexus avulsion, the phrenic nerve transfer to the musculocutaneous nerve has become part of clinical practice. The nerve transfer can be done by means of video-assisted thoracic surgery without nerve graft or via supraclavicular approach in combination with an autograft. This study focuses on a detailed microscopic and macroscopic examination of the phrenic nerve. It will allow a better interpretation of existing clinical results and, thus, serve as a basis for future clinical studies. MATERIAL AND METHODS: An anatomical study was conducted on 28 body donors of Caucasian origin (female n = 14, male n = 14). A sliding caliper and measuring tape were used to measure the diameter and length of the nerves. Sudan black staining was performed on 15 µm thick cryostat sections mounted on glass slides and the number of axons was determined by the ImageJ counting tool. In 23 individuals, the phrenic nerve could be examined on both sides. In 5 individuals, however, only one side was examined. Thus, a total of 51 nerves were examined. RESULTS: The mean length of the left phrenic nerves (33 cm (29-38 cm)) was significantly longer compared to the mean length of the right phrenic nerves (30 cm (24-33 cm)) (p < 0.001). Accessory phrenic nerves were present in 9 of 51 (18%) phrenic nerves. The mean number of phrenic nerves axons at the level of the first intercostal space in body donors with a right accessory phrenic nerve was significantly greater compared to the mean number of phrenic nerves axons at the same level in body donors without a right accessory phrenic nerve (3145 (range, 2688-3877) vs. 2278 (range, 1558-3276)), p = 0.034. A negative correlation was registered between age and the nerve number of axons in left (0.742, p < 0.001) and right (-0.273, p = 0.197) phrenic nerves. The mean distance from the upper edge of the ventral ramus of the fourth cervical spinal nerve to the point of entrance of the musculocutaneous nerve between the two parts of the coracobrachialis muscle was 19 cm (range, 15-24 cm) for the right and 20 cm (range, 15-25 cm) for the left arm. CONCLUSIONS: If an accessory phrenic nerve is available, it presumably should be spared. Thus, in that case, a supraclavicular approach in combination with a nerve graft would probably be of advantage.

A ratio to approximate the proximodistal extent of the flexor retinaculum in relation to the hand length.

The flexor retinaculum of the hand is a fibrous structure forming the carpal tunnel in conjunction with the carpal bones. To prevent incomplete release of the carpal tunnel it is of benefit to know about the expected longitudinal expansion of the flexor retinaculum. The objective of the present study was to identify a possible correlation between the proximodistal expansion of the flexor retinaculum and the length of the hand. We conducted an anatomical study on 124 hands of 62 body donors. The hand length and the length of the flexor retinaculum were measured in millimeters. By dividing the length of the flexor retinaculum by the hand length an individual ratio was calculated. The mean length of the observed hands was 187.8 mm. The mean proximodistal length of the flexor retinaculum was 27.2 mm (range, 14-39 mm). A positive correlation was noted between the proximodistal length of the flexor retinaculum and length of the hand (p = 0.01). On average, the length of the flexor retinaculum corresponded to 14% (range, 8-20%) of the hand length in right hands versus 15% (range, 11-20%) in left hands. A greater proximodistal length of the flexor retinaculum in longer hands compared to shorter hands can be expected. The length of the flexor retinaculum corresponds to 14-15% of the length of the hand. However, one should be aware that the length of the flexor retinaculum extends as far as 20 % of the length of the hand.

Treatment of partial thickness burns of the face with Acticoat7™ : A retrospective single center study.

BACKGROUND: The face is affected in more than 50% of patients with extensive burn trauma. Effective treatment is of importance to avoid hypertrophic scarring, functional impairment and social stigmatization. MATERIAL AND METHODS: All patients treated with Acticoat7™ due to superficial and deep partial thickness burns of the face between 2008 and 2017 at the intensive care unit (ICU) for burn trauma at the Department for Plastic and Reconstructive Surgery of the Medical University of Vienna were retrospectively analyzed. Patients were evaluated for the number of required dressing changes until complete re-epithelialization, bacterial colonization, potential complications and the need for primary and secondary surgery. RESULTS: A total of 100 patients were analyzed. It took a median dressing change rate of 1 (range 0-5) in the superficial partial thickness and 3 (range 1-11) in the deep partial thickness group. Conservative treatment of deep partial thickness wounds was possible in 79% and 17% of these patients required secondary scar revision. Although bacterial colonization of the wounds frequently occurred, wound infections were rarely observed. CONCLUSION: Acticoat7™ is a valuable dressing for treating superficial and deep partial thickness burn wounds of the face in an intensive care unit setting. It enables extended time intervals between dressing changes without an increased risk for complications.

Occupational reintegration after severe burn injury: a questionnaire study.

BACKGROUND: As a consequence of improved survival rates after burn injury occupational reintegration of burn survivors has gained increasing significance. We aimed to develop a precise patient questionnaire as a tool to evaluate factors contributing to occupational reintegration. MATERIAL AND METHODS: A questionnaire comprising 20 questions specifically evaluating occupational reintegration was developed under psychological supervision. The single-center questionnaire study was implemented in patients with burn injuries who were admitted to the 6­bed burn intensive care unit (BICU) of the General Hospital of Vienna, Austria (2004-2013). The questionnaire was sent to burn survivors of working age (18-60 years) with an abbreviated burn severity index (ABSI) of 6 or greater, a total burn surface area (TBSA) of 15% or greater, and a BICU stay of at least 24 h. RESULTS: A total of 112 burn survivors met the inclusion criteria and were contacted by mail. Of the 112 patients 11 (10%) decided to participate in the study and 218/220 questions (99%) in 11 patients were answered. Out of 11 patients 7 (64%) reported successful return to work and 4 of 11 (36%) did not resume their occupation. Advanced age, longer BICU and hospital stays, higher TBSA, burn at work, lower education, and problems with esthetic appearance seemed to impair patients' return to their occupation. CONCLUSION: When implementing the questionnaire, severely burned patients with higher age, lower education, and longer hospital and BICU stay seemed at high risk for failed reintegration in their profession after burn injury.

Bisegmental posterior stabilisation of thoracolumbar fractures with polyaxial pedicle screws: Does additional balloon kyphoplasty retain vertebral height?

We retrospectively evaluated single-level compression fractures (T12-L3) scheduled for a short-segment POS (posterior-only stabilization) using polyaxial screws. Patients averaged 55.7 years (range, 19-65). Patients received either POS or, concomitantly, BK (balloon kyphoplasty) of the fractured vertebrae as well. Primary endpoint was the radiological outcome at the last radiographic follow-up prior to implant removal. POS together with BK of the fractured vertebrae resulted in a significant improvement of the local kyphosis angle and vertebral body compression rates immediately post-OP. During the further course of FU, a considerable loss of correction was observed post-OP in both groups. (Local KA: pre-OP/ post-OP/ FU: 12.6±4.8/ 3.35±4.8/ 11.6±6.0; anterior vertebral body compression%: pre-OP/post-OP/ FU: 71.94±12.3/ 94.78±19.95/ 78.17±14.74). VAS was significantly improved from 7.2±1.3 pre-OP to 2.7±1.3 (P<0.001) at FU. We found a significant restoration of the vertebral body height by BK. Nevertheless, follow-up revealed a noticeable loss of reduction. Given the fact that BK used together with polyaxial screws did not maintain intra-operative reduction, our data do not support this additional maneuver when used together with bi-segmental polyaxial pedicle screw fixation.

Air-fluidized therapy in the treatment of severe burns: A retrospective study from a burn intensive care unit in Austria.

INTRODUCTION: Air-fluidized therapy (AFT) has long been used in the treatment of severe burns. In patients with extensive burns involving the posterior trunk, we aim to keep affected posterior areas dry and to postpone their treatment, initially applying available split-thickness skin grafts in functionally more important regions. We retrospectively assessed the impact of AFT on the survival of patients treated in the burn intensive care unit (ICU) of the Medical University of Vienna, Austria, between 2003 and 2016. METHODS: This retrospective single-center study included patients aged ≥18 years with burned total body surface area (TBSA) ≥20% and IIb-III° thermal injuries on the posterior trunk who received AFT. Survival rates were compared with those predicted by the abbreviated burn severity index (ABSI). Demographic, clinical, and surgical data were analyzed. RESULTS: Seventy-five of 110 patients with posterior trunk burns received AFT. Their survival rate exceeded that predicted by the ABSI score (mean ABSI, 10.0 ± 2.0; 73.3% (95% CI: 62-83%) survival rate vs. 20-40% predicted; p < 0.0001); no such difference was observed in the non-AFT group (mean, 8.8 ± 1.9; 65.7% (95% CI: 48-81%) survival rate vs. 50-70% predicted). Patients receiving AFT had significantly greater TBSA (median, 50% (35-60) vs. 30% (25-45) and longer ICU stays (median, 63 (36-92) vs. 18 (9-52) days; both p < 0.0001). Fifty-one (68.0%) patients in the AFT group and 26 (74.3%) patients in the non-AFT group underwent posterior trunk surgery (p = 0.66) a median of 16 (10-26) and 5 (2.5-9.5) days, respectively, after admission (p < 0.0001). CONCLUSIONS: Patients receiving AFT had significantly better survival than predicted by ABSI score in contrast to patients not receiving AFT although burn injuries in this group were more severe (greater TBSA, higher ABSI). As intensive care was similar in these groups aside from AFT, the better survival could be attributed to this additional therapy.

Incidence of risk factors for bloodstream infections in patients with major burns receiving intensive care: A retrospective single-center cohort study.

OBJECTIVES: The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens. METHODS: A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray. RESULTS: A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p<0.0001) and need for fasciotomy (p<0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p<0.0001). CONCLUSIONS: A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp.