Minimally Invasive Sympathicotomy for Palmar Hyperhidrosis and Facial Blushing: Current Status and the Hyperhidrosis Expert Center Approach.

Hyperhidrosis, the medical term for excessive sweating beyond physiological need, is a condition with serious emotional and social consequences for affected patients. Symptoms usually appear in focal areas such as the feet, hands, axillae and face. Non-surgical treatment options such as topical antiperspirants or systemic medications are usually offered as a first step of treatment, although these therapies are often ineffective, especially in severe and intolerable cases of hyperhidrosis. In the treatment algorithm for patients suffering from hyperhidrosis, surgical thoracoscopic sympathicotomy offers a permanent solution, which is particularly effective in the treatment of palmar hyperhidrosis and facial blushing. In this review, we describe the current status of thoracoscopic sympathicotomy for palmar hyperhidrosis and facial blushing. In addition, we share the specific treatment approach, technique and results of our Hyperhidrosis Expert Center. Last, we share recommendations to ensure an effective, reproducible and safe application of single-port thoracoscopic sympathicotomy for palmar hyperhidrosis and facial blushing, based on our extensive experience.

A translational rat model for ex vivo lung perfusion of pre-injured lungs after brain death.

The process of brain death (BD) detrimentally affects donor lung quality. Ex vivo lung perfusion (EVLP) is a technique originally designed to evaluate marginal donor lungs. Nowadays, its potential as a treatment platform to repair damaged donor lungs is increasingly studied in experimental models. Rat models for EVLP have been described in literature before, yet the pathophysiology of BD was not included in these protocols and prolonged perfusion over 3 hours without anti-inflammatory additives was not achieved. We aimed to establish a model for prolonged EVLP of rat lungs from brain-dead donors, to provide a reliable platform for future experimental studies. Rat lungs were randomly assigned to one of four experimental groups (n = 7/group): 1) healthy, directly procured lungs, 2) lungs procured from rats subjected to 3 hours of BD and 1 hour cold storage (CS), 3) healthy, directly procured lungs subjected to 6 hours EVLP and 4), lungs procured from rats subjected to 3 hours of BD, 1 hour CS and 6 hours EVLP. Lungs from brain-dead rats showed deteriorated ventilation parameters and augmented lung damage when compared to healthy controls, in accordance with the pathophysiology of BD. Subsequent ex vivo perfusion for 6 hours was achieved, both for lungs of healthy donor rats as for pre-injured donor lungs from brain-dead rats. The worsened quality of lungs from brain-dead donors was evident during EVLP as well, as corroborated by deteriorated ventilation performance, increased lactate production and augmented inflammatory status during EVLP. In conclusion, we established a stable model for prolonged EVLP of pre-injured lungs from brain-dead donor rats. In this report we describe tips and pitfalls in the establishment of the rat EVLP model, to enhance reproducibility by other researchers.

Ex Vivo Perfusion With Methylprednisolone Attenuates Brain Death-induced Lung Injury in Rats.

The onset of brain death (BD) leads to the deterioration of potential donor lungs. Methylprednisolone is considered to increase lung oxygenation capacity and enhance the procurement yield of donor lungs, when applied in situ, during donor management. However, whether BD-induced lung damage is ameliorated upon treatment with methylprednisolone during acellular ex vivo lung perfusion (EVLP), remains unknown. We aimed to investigate whether the quality of lungs from brain-dead donors improves upon methylprednisolone treatment during EVLP. METHODS: Rat lungs were randomly assigned to 1 of 3 experimental groups (n = 8/group): (1) healthy, directly procured lungs subjected to EVLP; (2) lungs from brain-dead rats subjected to cold storage and EVLP; and (3) lungs from brain-dead rats subjected to cold storage and EVLP with 40 mg methylprednisolone added to the perfusate. Ventilation and perfusion parameters, histology, edema formation, metabolic profile, and inflammatory status of lungs were investigated. RESULTS: Methylprednisolone treated lungs from brain-dead donors improved positive inspiratory pressures needed to maintain tidal volumes of 7 mL/kg of body weight, which was 25.6 ± 5.8 cm H2O in untreated lungs and 18.0 ± 3.0 cm H2O in methylprednisolone treated lungs, after 6 h EVLP. Furthermore, dynamic lung compliance increased upon methylprednisolone treatment, with values of 0.11 ± 0.05 mL/cm H2O versus 0.18 ± 0.04 mL/cm H2O after 6 h of EVLP. Methylprednisolone treatment ameliorated the amount of lung edema, as corroborated by a reduction of 0.7 in the wet/dry ratio. Although glucose consumption levels were comparable, the BD-induced cumulative lactate production decreased from 0.44 ± 0.26 to 0.11 ± 0.16 mmol/L upon methylprednisolone treatment. Finally, BD-induced inflammatory status was reduced upon methylprednisolone treatment compared to untreated lungs from brain-dead donors, as reflected by lower proinflammatory gene expression levels of IL-1ß, IL-6 and MCP-1, and IL-6 perfusate levels. CONCLUSIONS: We showed that methylprednisolone treatment during EVLP attenuates BD-induced lung injury.

Methylprednisolone Treatment in Brain Death-Induced Lung Inflammation-A Dose Comparative Study in Rats.

Background: The process of brain death (BD) leads to a pro-inflammatory state of the donor lung, which deteriorates its quality. In an attempt to preserve lung quality, methylprednisolone is widely recommended in donor lung management. However, clinical treatment doses vary and the dose-effect relation of methylprednisolone on BD-induced lung inflammation remains unknown. The aim of this study was to investigate the effect of three different doses methylprednisolone on the BD-induced inflammatory response. Methods: BD was induced in rats by inflation of a Fogarty balloon catheter in the epidural space. After 60 min of BD, saline or methylprednisolone (low dose (5 mg/kg), intermediate dose (12.5 mg/kg) or high dose (22.5 mg/kg)) was administered intravenously. The lungs were procured and processed after 4 h of BD. Inflammatory gene expressions were analyzed by RT-qPCR and influx of neutrophils and macrophages were quantified with immunohistochemical staining. Results: Methylprednisolone treatment reduced neutrophil chemotaxis as demonstrated by lower IL-8-like CINC-1 and E-selectin levels, which was most evident in rats treated with intermediate and high doses methylprednisolone. Macrophage chemotaxis was attenuated in all methylprednisolone treated rats, as corroborated by lower MCP-1 levels compared to saline treated rats. Thereby, all doses methylprednisolone reduced TNF-α, IL-6 and IL-1ß tissue levels. In addition, intermediate and high doses methylprednisolone induced a protective anti-inflammatory response, as reflected by upregulated IL-10 expression when compared to saline treated brain-dead rats. Conclusion: We showed that intermediate and high doses methylprednisolone share most potential to target BD-induced lung inflammation in rats. Considering possible side effects of high doses methylprednisolone, we conclude from this study that an intermediate dose of 12.5 mg/kg methylprednisolone is the optimal treatment dose for BD-induced lung inflammation in rats, which reduces the pro-inflammatory state and additionally promotes a protective, anti-inflammatory response.

Donor management using a specialized donor care facility is associated with higher organ utilization from drug overdose donors.

Drug overdoses have tripled in the United States over the last two decades. With the increasing demand for donor organs, one potential consequence of the opioid epidemic may be an increase in suitable donor organs. Unfortunately, organs from donors dying of drug overdose have poorer utilization rates than other groups of brain-dead donors, largely due to physician and recipient concerns about viral disease transmission. During the study period of 2011 to 2016, drug overdose donors (DODs) account for an increasingly greater proportion of the national donor pool. We show that a novel model of donor care, known as specialized donor care facility (SDCF), is associated with an increase in organ utilization from DODs compared to the conventional model of hospital-based donor care. This is likely related to the close relationship of the SDCF with the transplant centers, leading to improved communication and highly efficient donor care.

Brain death-induced lung injury is complement dependent, with a primary role for the classical/lectin pathway.

In brain-dead donors immunological activation occurs, which deteriorates donor lung quality. Whether the complement system is activated and which pathways are herein involved, remain unknown. We aimed to investigate whether brain death (BD)-induced lung injury is complement dependent and dissected the contribution of the complement activation pathways. BD was induced and sustained for 3 hours in wild-type (WT) and complement deficient mice. C3-/- mice represented total complement deficiency, C4-/- mice represented deficiency of the classical and lectin pathway, and factor properdin (P)-/- mice represented alternative pathway deficiency. Systemic and local complement levels, histological lung injury, and pulmonary inflammation were assessed. Systemic and local complement levels were reduced in C3-/- mice. In addition, histological lung injury and inflammation were attenuated, as corroborated by influx of neutrophils and gene expressions of interleukin (IL)-6, IL-8-like KC, TNF-α, E-selectin, and MCP-1. In C4-/- mice, complement was reduced on both systemic and local levels and histological lung injury and inflammatory status were ameliorated. In P-/- mice, histological lung injury was attenuated, though systemic and local complement levels, IL-6 and KC gene expressions, and neutrophil influx were not affected. We demonstrated that BD-induced lung injury is complement dependent, with a primary role for the classical/lectin activation pathway.

Rat donor lung quality deteriorates more after fast than slow brain death induction.

Donor brain death (BD) is initiated by an increase in intracranial pressure (ICP), which subsequently damages the donor lung. In this study, we investigated whether the speed of ICP increase affects quality of donor lungs, in a rat model for fast versus slow BD induction. Rats were assigned to 3 groups: 1) control, 2) fast BD induction (ICP increase over 1 min) or 3) slow BD induction (ICP increase over 30 min). BD was induced by epidural inflation of a balloon catheter. Brain-dead rats were sacrificed after 0.5 hours, 1 hour, 2 hours and 4 hours to study time-dependent changes. Hemodynamic stability, histological lung injury and inflammatory status were investigated. We found that fast BD induction compromised hemodynamic stability of rats more than slow BD induction, reflected by higher mean arterial pressures during the BD induction period and an increased need for hemodynamic support during the BD stabilization phase. Furthermore, fast BD induction increased histological lung injury scores and gene expression levels of TNF-α and MCP-1 at 0.5 hours after induction. Yet after donor stabilization, inflammatory status was comparable between the two BD models. This study demonstrates fast BD induction deteriorates quality of donor lungs more on a histological level than slow BD induction.

Blocking Complement Factor B Activation Reduces Renal Injury and Inflammation in a Rat Brain Death Model.

Introduction: The majority of kidneys used for transplantation are retrieved from brain-dead organ donors. In brain death, the irreversible loss of brain functions results in hemodynamic instability, hormonal changes and immunological activation. Recently, brain death has been shown to cause activation of the complement system, which is adversely associated with renal allograft outcome in recipients. Modulation of the complement system in the brain-dead donor might be a promising strategy to improve organ quality before transplantation. This study investigated the effect of an inhibitory antibody against complement factor B on brain death-induced renal inflammation and injury. Method: Brain death was induced in male Fischer rats by inflating a balloon catheter in the epidural space. Anti-factor B (anti-FB) or saline was administered intravenously 20 min before the induction of brain death (n = 8/group). Sham-operated rats served as controls (n = 4). After 4 h of brain death, renal function, renal injury, and inflammation were assessed. Results: Pretreatment with anti-FB resulted in significantly less systemic and local complement activation than in saline-treated rats after brain death. Moreover, anti-FB treatment preserved renal function, reflected by significantly reduced serum creatinine levels compared to saline-treated rats after 4 h of brain death. Furthermore, anti-FB significantly attenuated histological injury, as seen by reduced tubular injury scores, lower renal gene expression levels (>75%) and renal deposition of kidney injury marker-1. In addition, anti-FB treatment significantly prevented renal macrophage influx and reduced systemic IL-6 levels compared to saline-treated rats after brain death. Lastly, renal gene expression of IL-6, MCP-1, and VCAM-1 were significantly reduced in rats treated with anti-FB. Conclusion: This study shows that donor pretreatment with anti-FB preserved renal function, reduced renal damage and inflammation prior to transplantation. Therefore, inhibition of factor B in organ donors might be a promising strategy to reduce brain death-induced renal injury and inflammation.

Complement Therapeutics in the Multi-Organ Donor: Do or Don't?

Over the last decade, striking progress has been made in the field of organ transplantation, such as better surgical expertise and preservation techniques. Therefore, organ transplantation is nowadays considered a successful treatment in end-stage diseases of various organs, e.g. the kidney, liver, intestine, heart, and lungs. However, there are still barriers which prevent a lifelong survival of the donor graft in the recipient. Activation of the immune system is an important limiting factor in the transplantation process. As part of this pro-inflammatory environment, the complement system is triggered. Complement activation plays a key role in the transplantation process, as highlighted by the amount of studies in ischemia-reperfusion injury (IRI) and rejection. However, new insight have shown that complement is not only activated in the later stages of transplantation, but already commences in the donor. In deceased donors, complement activation is associated with deteriorated quality of deceased donor organs. Of importance, since most donor organs are derived from either brain-dead donors or deceased after circulatory death donors. The exact mechanisms and the role of the complement system in the pathophysiology of the deceased donor have been underexposed. This review provides an overview of the current knowledge on complement activation in the (multi-)organ donor. Targeting the complement system might be a promising therapeutic strategy to improve the quality of various donor organs. Therefore, we will discuss the complement therapeutics that already have been tested in the donor. Finally, we question whether complement therapeutics should be translated to the clinics and if all organs share the same potential complement targets, considering the physiological differences of each organ.

First experience with ex vivo lung perfusion for initially discarded donor lungs in the Netherlands: a single-centre study.

OBJECTIVES: Despite progress in lung transplantation (LTx) techniques, a shortage of donor lungs persists worldwide. Ex vivo lung perfusion (EVLP) is a technique that evaluates, optimizes and enables transplantation of the lungs that would otherwise have been discarded. Herein, we present our centre's first EVLP experiences between July 2012 and June 2016, when we performed 149 LTxs. METHODS: It was a single-centre, retrospective analysis of a prospectively collected database. The EVLP group (n = 9) consisted of recipients who initially received discarded donor lungs that were reconditioned using EVLP. The non-EVLP (N-EVLP) group (n = 18) consisted of data-matched patients receiving conventional quality lungs in the conventional way. Both groups were compared on primary graft dysfunction (PGD) grades 0-3, pulmonary function, chronic lung allograft dysfunction and survival. RESULTS: In the EVLP group, 33% (3/9) developed PGD1 at 72 h post-LTx. In the N-EVLP group, 11% (2/18) developed PGD1, 6% (1/18) PGD2 and 11% (2/18) PGD3 at 72 h post-LTx. At 3 and 24 months post-LTx, forced expiratory volume in 1 s as percentage of predicted was similar in the EVLP (78% and 92%) and N-EVLP groups (69% and 89%). Forced vital capacity as a percentage of predicted was comparable in the EVLP (77% and 93%) and N-EVLP groups (68% and 101%). Chronic lung allograft dysfunction was diagnosed in 1 N-EVLP patient at 2 years post-LTx. Three-year survival was 78% (7/9) (the EVLP group) vs 83% (15/18) (the N-EVLP group). CONCLUSIONS: These results are in line with the existing literature suggesting that transplantation of the previously discarded lungs recovered by EVLP leads to equal outcomes compared to conventional LTx methods.

Pain score, desire for pain treatment and effect on pain satisfaction in the emergency department: a prospective, observational study.

BACKGROUND: Pain management in the Emergency Department has often been described as inadequate, despite proven benefits of pain treatment protocols. The aim of this study was to investigate the effectiveness of our current pain protocol on pain score and patient satisfaction whilst taking the patients' wishes for analgesia into account. METHODS: We conducted a 10-day prospective observational study in the Emergency Department. Demographics, pain characteristics, Numeric Rating Scale pain scores and the desire for analgesics were noted upon arrival at the Emergency Department. A second Numeric Rating Scale pain score and the level of patient satisfaction were noted 75-90 min after receiving analgesics. Student T-tests, Mann-Whitney U tests and Kruskall-Wallis tests were used to compare outcomes between patients desiring vs. not desiring analgesics or patients receiving vs. not receiving analgesics. Univariate and multivariate logistic regression models were used to investigate associations between potential predictors and outcomes. RESULTS: In this study 334 patients in pain were enrolled, of which 43.7% desired analgesics. Initial pain score was the only significant predictive factor for desiring analgesia, and differed between patients desiring (7.01) and not desiring analgesics (5.14). Patients receiving analgesics (52.1%) had a greater decrease in pain score than patients who did not receive analgesics (2.41 vs. 0.94). Within the group that did not receive analgesics there was no difference in satisfaction score between patients desiring and not desiring analgesics (7.48 vs. 7.54). Patients receiving analgesics expressed a higher satisfaction score than patients not receiving analgesics (8.10 vs. 7.53). CONCLUSIONS: This study pointed out that more than half of the patients in pain entering the Emergency Department did not desire analgesics. In patients receiving analgesics, our pain protocol has shown to adequately treat pain, leading to a higher satisfaction for emergency health-care at discharge. This study emphasizes the importance of questioning pain score and desire for analgesics to prevent incorrect conclusions of inadequate pain management, as described in previous studies.