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.

Prevalence and clinical implications of bloodstream infections in intensive care patients with or without burn injury: a retrospective cohort study.

PURPOSE: Severe burn injuries are often accompanied by infections and associated with high morbidity and mortality. This study aimed to compare the prevalence and clinical impact of bacteremia between patients receiving intensive care with and without burns. METHODS: This single-center retrospective cohort study at the University Hospital Vienna, Austria, analyzed blood cultures from intensive care unit (ICU) patients with and without burns (2012-2022) to assess the prevalence of bacteremia, the associated pathogen distribution and the 60-day all-cause mortality. RESULTS: In 1170 ICU patients, 303 with burns and 867 without, the prevalence of bacteremia was similar among patients with at least one blood culture (31/157 [19.7%] versus 44/213 [20.7%], OR [95%CI] = 0.95 [0.57-1.57]). Burn patients exhibited a significantly higher frequency of microbiological sampling (51.5% versus 24.5%, p < 0.001), resulting in a higher overall prevalence of bacteremia (10.2% versus 5.1%, p = 0.002). 16.2% of all identified pathogens were multidrug-resistant (MDR). The 60-day all-cause mortality was higher in patients with MDR pathogens than in patients without bacteremia (41.7% versus 10.6%, p = 0.026). CONCLUSION: Bacteremia prevalence was similar in burn and non-burn patients, with high rates of multidrug-resistant Gram-negative pathogens. The 60-day all-cause mortality was significantly higher in patients with MDR pathogens than in patients without bacteremia.

Community-acquired and hospital-acquired bacterial co-infections in patients hospitalized with Covid-19 or influenza: a retrospective cohort study.

BACKGROUND: Bacterial co-infections are believed to be less frequent in patients with Covid-19 than influenza, but frequencies varied between studies. METHODS: This single-center retrospective, propensity score-matched analysis included adult patients with Covid-19 or influenza admitted to normal-care wards between 02/2014 and 12/2021. Covid-19 cases were propensity score matched to influenza cases at a 2:1 ratio. Community-acquired and hospital-acquired bacterial co-infections were defined as positive blood or respiratory cultures ≤ 48 h or > 48 h after hospital admission, respectively. The primary outcome was comparison of community-acquired and hospital-acquired bacterial infections between patients with Covid-19 and influenza in the propensity score-matched cohort. Secondary outcomes included frequency of early and late microbiological testing. RESULTS: A total of 1337 patients were included in the overall analysis, of which 360 patients with Covid-19 were matched to 180 patients with influenza. Early (≤ 48 h) microbiological sampling was performed in 138 (38.3%) patients with Covid-19 and 75 (41.7%) patients with influenza. Community-acquired bacterial co-infections were found in 14 (3.9%) of 360 patients with Covid-19 and 7 (3.9%) of 180 patients with influenza (OR 1.0, 95% CI 0.3-2.7). Late (> 48 h) microbiological sampling was performed in 129 (35.8%) patients with Covid-19 and 74 (41.1%) patients with influenza. Hospital-acquired bacterial co-infections were found in 40 (11.1%) of 360 patients with Covid-19 and 20 (11.1%) of 180 patients with influenza (OR 1.0, 95% CI 0.5-1.8). CONCLUSION: The rate of community-acquired and hospital-acquired bacterial co-infections was similar in hospitalized Covid-19 and influenza patients. These findings contrast previous literature reporting that bacterial co-infections are less common in Covid-19 than influenza.

Management of an Early-Onset, Painful Tibial Nerve Neuroma Using an Autologous Nerve Graft.

This case report describes the treatment of a postoperative painful neuroma of the tibial nerve using an autologous nerve graft in a dog. The patient presented with sudden non-weight-bearing lameness 10 days after iatrogenic tibial nerve injury during preparation of a reverse saphenous conduit flap. The dog showed severe pain at the surgical site without nerve deficits. A magnetic resonance imaging examination revealed an enlarged tibial nerve at the injury site, consistent with a neuroma. Analgesics were administered over 11 days, but the patient remained in severe pain and non-weight-bearing. Therefore, surgical resection was recommended. The fusiform neuroma was resected microsurgically, and a saphenous nerve graft was transplanted using an epineural nerve repair technique. Histopathological examination was consistent with a neuroma. The dog showed immediate pain relief and weight-bearing the day after surgery with normal motor function. The dog made a full recovery by the last follow-up 6 mo after surgery. If patients develop pain and lameness following surgery or nerve injury, neuroma formation must be considered, even shortly after surgery. Microsurgical resection and autologous nerve transplantation using an epineural nerve repair technique is a viable method to treat painful neuromas and minimize the risk for recurrence in dogs.

Schwann cell stimulation induces functional and structural changes in peripheral nerves.

Signal propagation is the essential function of nerves. Lysophosphatidic acid 18:1 (LPA) allows the selective stimulation of calcium signaling in Schwann cells but not neurons. Here, the time course of slowing and amplitude reduction on compound action potentials due to LPA exposure was observed in myelinated and unmyelinated fibers of the mouse, indicating a clear change of axonal function. Teased nerve fiber imaging showed that Schwann cell activation is also present in axon-attached Schwann cells in freshly isolated peripheral rat nerves. The LPA receptor 1 was primarily localized at the cell extensions in isolated rat Schwann cells, suggesting a role in cell migration. Structural investigation of rat C-fibers demonstrated that LPA leads to an evagination of the axons from their Schwann cells. In A-fibers, the nodes of Ranvier appeared unchanged, but the Schmidt-Lanterman incisures were shortened and myelination reduced. The latter might increase leak current, reducing the potential spread to the next node of Ranvier and explain the changes in conduction velocity. The observed structural changes provide a plausible explanation for the functional changes in myelinated and unmyelinated axons of peripheral nerves and the reported sensory sensations such as itch and pain.

Efficacy and Safety of Corticosteroid Therapy for Community-Acquired Pneumonia: A Meta-Analysis and Meta-Regression of Randomized, Controlled Trials.

BACKGROUND: Community-acquired pneumonia (CAP) is associated with high morbidity and mortality. In the present study, we aimed to assess the effect of corticosteroids on all-cause mortality in patients hospitalized with CAP. METHODS: For this meta-analysis and meta-regression, we conducted a systematic search of trials that evaluated the effect of corticosteroid therapy in patients hospitalized with CAP through March 2023. We included randomized, controlled trials, comparing adjunctive corticosteroid therapy with the standard of care alone for treatment of patients hospitalized with CAP and reporting all-cause mortality. We excluded retrospective analyses, observational data, and trial protocols. The primary outcome was all-cause mortality within 30 days after hospital admission. The safety analysis included the frequency of adverse events and steroid-associated adverse events. RESULTS: The literature search identified 35 713 citations, of which 15 studies and 3367 patients were eligible for the final analysis. The all-cause mortality at 30 days was significantly lower in the corticosteroid group (104 of 1690, 6.15%) than in the control group (152 of 1677, 9.06%; risk ratio [RR], 0.67; 95% confidence interval [CI], .53 to .85; P = .001; I2 = 0%). In 9 studies (2549 patients) that reported the occurrence of adverse events, corticosteroid therapy was not associated with an increased risk of developing any adverse event compared with standard care (RR, 0.90; 95% CI, .65 to 1.24; P = .5; I2 = 88%). CONCLUSIONS: Adjunctive systemic corticosteroid therapy in patients hospitalized with CAP was associated with a reduction in all-cause mortality by day 30. The benefits were more pronounced in patients with severe pneumonia.

Defining the regenerative effects of native spider silk fibers on primary Schwann cells, sensory neurons, and nerve-associated fibroblasts.

The search for a suitable material to promote regeneration after long-distance peripheral nerve defects turned the spotlight on spider silk. Nerve conduits enriched with native spider silk fibers as internal guiding structures previously demonstrated a regenerative outcome similar to autologous nerve grafts in animal studies. Nevertheless, spider silk is a natural material with associated limitations for clinical use. A promising alternative is the production of recombinant silk fibers that should mimic the outstanding properties of their native counterpart. However, in vitro data on the regenerative features that native silk fibers provide for cells involved in nerve regeneration are scarce. Thus, there is a lack of reference parameters to evaluate whether recombinant silk fiber candidates will be eligible for nerve repair in vivo. To gain insight into the regenerative effect of native spider silk, our study aims to define the behavioral response of primary Schwann cells (SCs), nerve-associated fibroblasts (FBs), and dorsal root ganglion (DRG) neurons cultured on native dragline silk from the genus Nephila and on laminin coated dishes. The established multi-color immunostaining panels together with confocal microscopy and live cell imaging enabled the analysis of cell identity, morphology, proliferation, and migration on both substrates in detail. Our findings demonstrated that native spider silk rivals laminin coating as it allowed attachment and proliferation and supported the characteristic behavior of all tested cell types. Axonal out-growth of DRG neurons occurred along longitudinally aligned SCs that formed sustained bundled structures resembling Bungner bands present in regenerating nerves. The migration of SCs along the silk fibers achieved the reported distance of regenerating axons of about 1 mm per day, but lacked directionality. Furthermore, rFBs significantly reduced the velocity of rSCs in co-cultures on silk fibers. In summary, this study (a) reveals features recombinant silk must possess and what modifications or combinations could be useful for enhanced nerve repair and (b) provides assays to evaluate the regenerative performance of silk fibers in vitro before being applied as internal guiding structure in nerve conduits in vivo.

How miRNAs Regulate Schwann Cells during Peripheral Nerve Regeneration-A Systemic Review.

A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine.

Evaluation of patients after different types of secondary cleft palate repair.

The aim of this retrospective study was to evaluate results of four different surgical approaches to palatoplasty and to demonstrate which type showed the lowest number of cases with the need for secondary surgeries. The results of 227 patients who underwent cleft palate surgical repair over a 13-year period (2000-2012) were included. The incidence rates of oronasal fistula, velopharyngeal insufficiency with the need of pharyngeal flap and pharyngoplasty were examined. The need for revision surgery was found in 48 patients (21.1 %). A significantly higher rate of cases with the need for secondary correction was found in patients with a complete cleft (44 %) as compared to patients with incomplete cleft palate (9.8 %). A higher percentage for additional surgery was noted after the Bardach procedure (50 %) as opposed to the lower revision rate after Veau-Wardill-Kilner (22.8 %) and Furlow (17.6 %). After the von Langenbeck procedure, the need for revision eventuated only in 5.5 % of cases. It is important to mention that there were no significant differences in the incidence of secondary surgery between the patients with cleft palate with or without the presence of Pierre Robin sequence. Neither there was observed a significant difference in the incidence of additional surgery between male and female patients. However, a higher need for pharyngeal flap was noted in the female group (Tab. 8, Ref. 38). Keywords: complications after palatoplasty, cleft repair techniques, Pierre Robin sequence, pharyngeal flap.

Deciphering the functional heterogeneity of skin fibroblasts using single-cell RNA sequencing.

Though skin fibroblasts (FB) are the main cell population within the dermis, the different skin FB subsets are not well characterized and the traditional classification into reticular and papillary FBs has little functional relevance. To fill the gap of knowledge on FB diversity in human skin, we performed single-cell RNA sequencing. Investigation of marker genes for the different skin cell subtypes revealed a heterogeneous picture of FBs. When mapping reticular and papillary FB markers, we could not detect cluster specificity, suggesting that these two populations show a higher transcriptional heterogeneity than expected. This finding was further confirmed by in situ hybridization, showing that DPP4 was expressed in both dermal layers. Our analysis identified six FB clusters with distinct transcriptional signatures. Importantly, we could demonstrate that in human skin DPP4+ FBs are the main producers of factors involved in extracellular matrix (ECM) assembly. In conclusion, we provide evidence that hitherto considered FB markers are not ideal to characterize skin FB subpopulations in single-cell sequencing analyses. The identification of DPP4+ FBs as the main ECM-producing cells in human skin will foster the development of anti-fibrotic treatments for the skin and other organs.

Reconstruction of Critical Nerve Defects Using Allogenic Nerve Tissue: A Review of Current Approaches.

Regardless of the nerve defect length, nerve injury is a debilitating condition for the affected patient that results in loss of sensory and motor function. These functional impairments can have a profound impact on the patient's quality of life. Surgical approaches for the treatment of short segment nerve defects are well-established. Autologous nerve transplantation, considered the gold standard, and the use of artificial nerve grafts are safe and successful procedures for short segment nerve defect reconstruction. Long segment nerve defects which extend 3.0 cm or more are more problematic for repair. Methods for reconstruction of long defects are limited. Artificial nerve grafts often fail to regenerate and autologous nerve grafts are limited in length and number. Cadaveric processed/unprocessed nerve allografts are a promising alternative in nerve surgery. This review gives a systematic overview on pre-clinical and clinical approaches in nerve allograft transplantation.

Nanocellulose-based wound dressing for conservative wound management in children with second-degree burns.

The initial care of burn wounds and choice of dressing are pivotal to optimally support the healing process. To ensure fast re-epithelialisation within 10-14 days and prevent complications, an optimal healing environment is essential. An innovative dressing based on nanocellulose was used for the treatment of burns in children. Children (0-16 years) with clean, partial-thickness burn wounds, 1 to 10% of the total body surface area were included. Complete re-epithelialisation was achieved within 7-17 days, with 13 patients showing re-epithelialised >95% by day 10. Satisfying results concerning time to re-epithelialisation and material handling were obtained. The possibility to leave the dressing on the wounds for 7 days showed a positive effect in the treatment of children, for whom every hospital visit may cause massive stress reactions. The nanocellulose-based dressing is a promising tool in conservative treatment of burns. Reducing the frequency of dressing changes supports a fast and undisturbed recovery; moreover, the dressing provides an optimal moist healing environment. The time to re-epithelialisation is comparable to frequently used materials, and cost reduction effect can be achieved without loss of quality. Possible pain and distress levels are kept to a minimum; therefore, flexibility and compliance of the patients and their parents are enhanced.

Does obesity impact the outcome of severely burned patients?

Although obesity appears to be an important predictor of mortality and morbidity, little data about the impact of body mass index (BMI) on the outcome of severely burned patients are available. Patients admitted to the General Hospital Vienna between 1994 and 2014, who underwent surgery because of burn injuries, were enrolled in this study. BMI was used to divide patients into five groups: BMI 18.5 to 24.9, 25 to 29.9, 30 to 34.9, 35 to 39.9, and > 40. The groups were compared in terms of difference of mortality and morbidity. Of 460 patients, 34.3% (n = 158) died. Mortality rates were the lowest in patients with obesity class III and the highest in patients with BMI 35 to 39.9 (BMI 18.5-24.9: 30.5%, BMI 25-29.9: 31.5%, BMI 30-34.9: 41.3%, BMI 35-39.9: 55.5%, BMI > 40: 30%; P = .031). BMI was not found to be an independent risk factor when corrected with age, percent total body surface area burned, full-thickness burns, and inhalation injury. No significant differences in length of stay, inhalation trauma, pneumonia, wound infection, sepsis, and invasive ventilation were observed. BMI as an independent risk factor for severely burned patients could not be confirmed via multivariate analysis.

Anatomical Study of a Chimeric Fascio-Osteomyocutaneous Fibula Flap for Free Microvascular Tissue Transfer.

BACKGROUND: Functional restoration in reconstructive surgery can require complex and adaptable approaches. In this anatomical study, the combined angiosome of the septofasciomyocutaneous vessels originating from the fibular artery was defined as basis for a chimeric flap of the lateral lower leg. METHODS: Methylene blue injection into the fibular artery was performed in 10 legs of fresh cadavers for visualization of the angiosome on the skin, fibula, and adjacent muscles as the lateral hemisoleus (HS) muscle. With regards to clinical specifications a maximum-size flap containing cutaneous, osseous, and muscular elements was raised. During dissection, the distribution pattern, number and size of stained septofasciomyocutaneous vessels at the lateral border of the proximal, middle, and distal thirds of the fibula length, as well as the flap dimensions were evaluated. RESULTS: In all specimens, vessels originating from the fibular artery and supplying the resected fibular bone, the fasciocutaneous flap and dorsally located muscles were found. The mean number of vessels to the skin was 4.2 per leg with a mean diameter of 1.1 ± 0.5 mm (range: 0.4-2.5 mm) and to the HS muscle 3.4 vessels with a mean diameter of 1.2 ± 0.7 mm (range: 0.3-3.0 mm). A total of 88.4% vessels occurred in the proximal and middle thirds of the legs. The resected fibula graft had a mean length of 23.8 ± 3.9 cm (range: 19.9-31.0 cm) and the skin paddle had a mean size of 23.8 ± 3.9 cm (range: 19.9-31.0 cm) × 7.0 cm. The flexor hallucis longus (FHL) muscle had a mean volume of 37.2 ± 15.8 cm3 (range: 18-58 cm3) and the lateral HS muscle 77.1 ± 23.3 cm3 (range: 48-105 cm3). CONCLUSION: Our results and anatomical descriptions indicate that chimeric fibula flaps can meet the specific reconstructional requirements of complex and large sized defects representing a promising basis for further studies.

Hydrogen peroxide (H2O2): a review of its use in surgery.

Hydrogen peroxide has been used in medicine for more than 100 years. It is known in surgery as a highly useful irrigation solution by virtue of both its hemostatic and its antimicrobial effects. Due to its possible negative effect on wound healing and its cytotoxic effect in higher concentrations, there are concerns about the safety of its use. The objective of this paper is to review the safety and beneficial effects of hydrogen peroxide.

Nerve grafting for peripheral nerve injuries with extended defect sizes.

Artificial and non-artificial nerve grafts are the gold standard in peripheral nerve reconstruction in cases with extensive loss of nerve tissue, particularly where a direct end-to-end suture or an autologous nerve graft is inauspicious. Different materials are marketed and approved by the US Food and Drug Administration (FDA) for peripheral nerve graft reconstruction. The most frequently used materials are collagen and poly(DL-lactide-ε-caprolactone). Only one human nerve allograft is listed for peripheral nerve reconstruction by the FDA. All marketed nerve grafts are able to demonstrate sufficient nerve regeneration over small distances not exceeding 3.0 cm. A key question in the field is whether nerve reconstruction on large defect lengths extending 4.0 cm or more is possible. This review gives a summary of current clinical and experimental approaches in peripheral nerve surgery using artificial and non-artificial nerve grafts in short and long distance nerve defects. Strategies to extend nerve graft lengths for long nerve defects, such as enhancing axonal regeneration, include the additional application of Schwann cells, mesenchymal stem cells or supporting co-factors like growth factors on defect sizes between 4.0 and 8.0 cm.

Bladder augmentation in children: current problems and experimental strategies for reconstruction.

Bladder augmentation is a demanding surgical procedure and exclusively offered for selected children and has only a small spectrum of indications. Paediatric bladder voiding dysfunction occurs either on a basis of neurological dysfunction caused by congenital neural tube defects or on a basis of rare congenital anatomic malformations. Neurogenic bladder dysfunction often responds well to a combination of specific drugs and/or intermittent self-catheterization. However, selected patients with spinal dysraphism and children with congenital malformations like bladder exstrophy and resulting small bladder capacity might require bladder augmentation. Ileocystoplasty is the preferred method of bladder augmentation to date. Because of the substantial long-and short-term morbidity of augmentation cystoplasty, recent studies have tried to incorporate new techniques and technologies, such as the use of biomaterials to overcome or reduce the adverse effects. In this regard, homografts and allografts have been implemented in bladder augmentation with varying results, but recent studies have shown promising data in terms of proliferation of urothelium and muscle cells by using biological silk grafts.

The Regenerative Capability of the Urodele Amphibians and Its Potential for Plastic Surgery.

Newts and salamanders, both urodele amphibians, are the only vertebrates with tremendous regenerative potency throughout their lifetime. In contrast to the limited regenerative potential of most mammals, including humans, they can regenerate an entire limb after amputation and many other structures of their bodies, whereas humans mainly respond to injury by the formation of a scar. The intention of plastic surgery is to restore function of injured body parts, with the highest principle to replace "like with like." Despite tremendous improvements in surgical techniques over the last century, the remaining drawbacks include the availability of autologous tissue for transfer to restore extensive tissue loss. Here, some regenerative features of the urodeles are reviewed, in particular wound healing, nerve and limb regeneration, and their potential impact for reconstructive surgery are discussed. With a detailed molecular and cellular understanding of the urodele regeneration processes in combination with recent advances in tissue engineering, new perspectives for plastic surgery and especially improvements in regards to tissue regeneration are opened.

Optimization of breast reconstruction results using TMG flap in 30 cases: Evaluation of several refinements addressing flap design, shaping techniques, and reduction of donor site morbidity.

BACKGROUND: The transverse myocutaneous gracilis (TMG) flap is a widely used alternative to abdominal flaps in autologous breast reconstruction. However, secondary procedures for aesthetic refinement are frequently necessary. Herein, we present our experience with an optimized approach in TMG breast reconstruction to enhance aesthetic outcome and to reduce the need for secondary refinements. METHODS: We retrospectively analyzed 37 immediate or delayed reconstructions with TMG flaps in 34 women, performed between 2009 and 2015. Four patients (5 flaps) constituted the conventional group (non-optimized approach). Thirty patients (32 flaps; modified group) underwent an optimized procedure consisting of modified flap harvesting and shaping techniques and methods utilized to reduce denting after rib resection and to diminish donor site morbidity. RESULTS: Statistically significant fewer secondary procedures (0.6 ± 0.9 versus 4.8 ± 2.2; P < .001) and fewer trips to the OR (0.4 ± 0.7 versus 2.3 ± 1.0 times; P = .001) for aesthetic refinement were needed in the modified group as compared to the conventional group. In the modified group, 4 patients (13.3%) required refinement of the reconstructed breast, 7 patients (23.3%) underwent mastopexy/mammoplasty or lipofilling of the contralateral breast, and 4 patients (13.3%) required refinement of the contralateral thigh. Total flap loss did not occur in any patient. Revision surgery was needed once. CONCLUSIONS: Compared to the conventional group, enhanced aesthetic results with consecutive reduction of secondary refinements could be achieved when using our modified flap harvesting and shaping techniques, as well as our methods for reducing contour deformities after rib resection and for overcoming donor site morbidities.