Botulinum Toxin A in the treatment of frostbite sequelae - results from a blinded, early-phase, comparative trial.

INTRODUCTION: Freezing Cold Injuries (FCI) have been associated with long-term sequelae including vasospasm. The aims of the pilot study are to explore the research methodology and investigate the tolerability and safety of treatment with Botulinum Toxin-A (BTX-A) in FCI Sequelae. METHODOLOGY: This pilot study tests the logistics, the treatment setting and the follow-up procedure in an early-phase, double-blinded, randomized, controlled trial study-design. The variables in the study were subjective symptoms, peripheral micro-vascularization/rewarming, somatosensory responsiveness, and generic measure of health status. RESULTS: No major challenges or difficulties were noticed according to the protocol or the study methodology. The monitoring of tolerability and safety of treatment with BTX-A did not reveal any major unwanted and/or adverse reactions among the patients in the pilot study and no challenges occurred during data collection of endpoints. The study revealed an inaccuracy of the 2nd degree FCI diagnosis and uncover a need for relevant and sufficient clinical information for FCI classification. CONCLUSIONS: This pilot study showed the study methodology with minor adjustments is feasible in a future full-scale clinical trial. The recruitment process needs to be more refined to ensure that the eligible study participants are a homogenous group of FCI patients.

Health effects of voluntary exposure to cold water - a continuing subject of debate.

This review is based on a multiple database survey on published literature to determine the effects on health following voluntary exposure to cold-water immersion (CWI) in humans. After a filtering process 104 studies were regarded relevant. Many studies demonstrated significant effects of CWI on various physiological and biochemical parameters. Although some studies were based on established winter swimmers, many were performed on subjects with no previous winter swimming experience or in subjects not involving cold-water swimming, for example, CWI as a post-exercise treatment. Clear conclusions from most studies were hampered by the fact that they were carried out in small groups, often of one gender and with differences in exposure temperature and salt composition of the water. CWI seems to reduce and/or transform body adipose tissue, as well as reduce insulin resistance and improve insulin sensitivity. This may have a protective effect against cardiovascular, obesity and other metabolic diseases and could have prophylactic health effects. Whether winter swimmers as a group are naturally healthier is unclear. Some of the studies indicate that voluntary exposure to cold water has some beneficial health effects. However, without further conclusive studies, the topic will continue to be a subject of debate.

Abstracts from The Cold Weather Operations Conference 2021.

A common effort for both military and civil healthcare is to achieve knowledge-based health care in cold weather injuries and fatal accidents in harsh arctic environment. The Cold Weather Operations Conference in November 2021, having more than 300 participants from 20 countries, was addressing the prevention and treatment of injuries and trauma care in cold weather conditions and the challenges for military prehospital casualty care. The intention of the programme was to stimulate further research and systematic knowledge-based clinical work. The abstracts from the conference present cold weather research and clinical experience relevant for readers of the International Journal of Circumpolar Health.

Liberal versus Modified Intraoperative Fluid Management in Abdominal-flap Breast Reconstructions. A Clinical Study.

BACKGROUND: The outcome of reconstructive microsurgery is influenced by the intraoperative anesthetic regimen. The aim of this study was to compare the impact on the intra- and postoperative complication rates of our modified fluid management (MFM) protocol with a previously used liberal fluid management protocol in abdominal-flap breast reconstructions. METHODS: This retrospective study analyzed adverse events related to secondary unilateral abdominal-flap breast reconstructions in two patient cohorts, one with a liberal fluid management protocol and one with a MFM protocol. In the MFM protocol, intravenous fluid resuscitation was restricted and colloid use was minimized. Both noradrenaline and propofol were implemented as standard in the MFM protocol. The primary endpoints were surgical and medical complications, as observed intraoperatively or postoperatively, during or shortly after the hospital stay. RESULTS: Of the 214 patients included in the study, 172 patients followed the MFM protocol. Prior radiotherapy was more frequent in the MFM protocol. Surgical procedures to achieve venous superdrainage were more often used in the MFM cohort. Intraoperative as well as postoperative complications occurred significantly more frequently in the liberal fluid management cohort and were specifically associated with partial and total flap failures. Prior radiotherapy, additional venous drainage, or choice of inhalation agent did not have an observable impact on outcome. CONCLUSIONS: The incidence of adverse events during and after autologous breast reconstructive procedures was reduced with the introduction of an MFM protocol. Strict intraoperative fluid control combined with norepinephrine and propofol was both beneficial and safe.

In Vivo Perforasome Perfusion in Hemi-DIEP Flaps Evaluated with Indocyanine-green Fluorescence Angiography and Infrared Thermography.

There are no in vivo studies that evaluate the effect of perforator dissection on the perfusion territory of a perforator (perforasome). In this study, indocyanine green fluorescence angiography (ICG-FA) and infrared thermography (IRT) were used intraoperatively to evaluate perforasome perfusion in hemi-DIEP flaps. METHODS: Patients selected for DIEP breast reconstruction were prospectively included in the study. Preoperative perforator mapping was performed with CTA and handheld Doppler ultrasound. In general anesthesia, perforasome perfusion was evaluated with ICG-FA and IRT both before surgery and after flap dissection with preserved dominant perforators. RESULTS: Thirty hemi-DIEP flaps were dissected in 15 patients (average BMI 26.6 kg/m2), of which 40% had been operated on in the lower abdomen. Fluorescence spots from ICG were associated with infrared radiation hotspots on IRT and these corresponded with the locations of the selected perforators. IRT and ICG-FA demonstrated similar patterns in perforasome perfusion before and after perforator dissection. Perforator dissection changed the perforasome perfusion. IRT made it possible to continuously monitor the perforator activity during surgery. ICG-FA easily identified areas with impaired flap perfusion due to previous surgery. CONCLUSIONS: Perforasome perfusion is a dynamic process that changes with perforator dissection. ICG-FA and IRT are reproducible techniques for in vivo evaluation of perforasome perfusion and produce comparable results.

Impact on Abdominal Skin Perfusion following Abdominoplasty.

Wound healing problems following abdominoplasty may be a result of impaired tissue perfusion. This study evaluated the impact a standard abdominoplasty may have on abdominal skin perfusion. METHODS: A standard abdominoplasty was performed in 16 patients. Dynamic infrared thermography (DIRT) using a mild and a stronger cold challenge was performed pre-, intra-, and postoperatively on day 1, 2, and in week 6. The abdomen was divided into Huger's vascular zones. A two-tailed t test was used to evaluate differences in mean temperature between zones. Statistical significance was defined as P < 0.05. RESULTS: Two patients suffered wound healing problems. Abdominal skin perfusion showed a hyperaemic state on day 1, day 2, and week 6, postoperatively. Hotspots in zones I and II had all disappeared at the end of surgery and on day 1, except in the cranial part of zone I. Hotspots reappeared in zones I and II during day 2. A statistically significant difference between zones I and II was seen on day 1 and 2, with zone II being cooler. This difference had disappeared in week 6 for the mild cold challenge but not for the stronger cold challenge. CONCLUSIONS: A standard abdominoplasty has a significant impact on abdominal skin perfusion. The skin perfusion is a dynamic process with a gradual improvement over time. The strongest effect was seen in zone II near the lower transverse incision line, where skin perfusion was the least. Such may contribute to impaired wound healing at this site.

A New Extraperitoneal Method for Entero-atmospheric Fistula Closure Using a Free Muscle Flap.

Treatment of an entero-atmospheric fistula (EAF) is challenging and associated with significant morbidity and mortality. For an EAF with protrusion of mucosa, chances for spontaneous closure are minimal. Standard surgical procedures may be associated with a high risk for complications in patients with a hostile abdomen. This article describes a new method for extraperitoneal closure of an EAF in a patient with a hostile abdomen. A free segmental latissimus dorsi musculocutaneous flap was harvested on its thoracodorsal pedicle, leaving the remaining muscle innervated. The flap was anastomosed to the internal mammary vessels. The muscle was sutured into the fistula opening using a parachute technique and temporarily immobilized with a negative wound pressure device. The skin of the flap was used for monitoring and later replaced by a skin graft. The postoperative course was uneventful. At 24 months follow-up, there were no signs of recurrences. The patient had no pain and had no defecation problems. Extraperitoneal closure of an EAF with a segmental free latissimus dorsi muscle flap sutured into the fistula opening with a parachute technique may be a new promising technique in patients where standard surgical procedures are associated with too high a risk for complications and where a local pedicled muscle flap is not available. The advantages of this method are that no laparotomy is required, the intestinal lumen is not reduced in diameter, and that no bowel resection is performed, which is a particular advantage in cases with a short bowel syndrome.

The Value of Dynamic Infrared Thermography in Pedicled Thoracodorsal Artery Perforator Flap Surgery.

Dynamic infrared thermography (DIRT) is a noninvasive imaging technique that can provide indirect and real-time information on skin perfusion by measuring skin temperature. Although used in flap surgery, there are no reports on its value in procedures using a pedicled thoracodorsal artery perforator (TDAP) flap. The aim of this study was to assess the usefulness of DIRT in preoperative perforator mapping and in monitoring intra- and postoperative flap perfusion of pedicled TDAP flaps. METHODS: This prospective study comprised 21 patients (21 flaps) scheduled for reconstructive surgery with a TDAP flap. Perforator mapping was done by DIRT, handheld unidirectional Doppler ultrasound, and computer tomography angiography. Intra- and postoperative flap perfusion was assessed by clinical signs and with the use of DIRT and handheld unidirectional Doppler ultrasound. RESULTS: Perforator mapping with DIRT showed that first-appearing bright hotspots were always associated with arterial Doppler sounds and suitable perforators intraoperatively. Computer tomography angiography presented useful information on the thoracodorsal artery branching pattern but was less beneficial for perforator mapping. Intra- and postoperative flap monitoring with DIRT was more useful than handheld unidirectional Doppler ultrasound and clinical signs to detect early arterial and venous perfusion problems. DIRT demonstrated that TDAP flap perfusion is a dynamic process with an increase in perfusion during the first operative days. Nineteen flaps survived, of which 3 sustained distal necrosis. Two flaps were lost due to inadequate blood perfusion. CONCLUSION: DIRT provides valuable real-time information for perforator mapping and for monitoring TDAP flap perfusion intra- and postoperatively.

Triple Use of Autologous Amnion Graft in the Treatment of Meningomyelocele and Split Cord Malformation.

This article describes the triple use of autologous amnion graft as a new procedure in the treatment of myelomeningocele and in myelomeningocele with split cord malformation. The first amnion graft was used as a physical and mechanical barrier to protect the myelomeningocele (MMC) from desiccation and mechanical stress directly after birth. A second graft was used as a dura substitute to close the cerebrospinal fluid compartment. Autologous amnion seems to be the ideal dural graft for closure of an MMC and for an MMC with split cord malformation. A tension-free and watertight closure was obtained. With the epithelium side placed to the spinal cord and due to its beneficial effect on scar formation, the risk for tethering cord syndrome is reduced when using autologous amnion as a dural graft. The regenerative properties of autologous amnion may contribute to repair neural damage. Finally, a third amnion graft was placed beneath the perforator flap used to close the skin defect to provide a watertight barrier and to stimulate flap survival.

Intrathoracic Breast Transposition: A New Method in the Treatment of Bronchopleural Fistula and Empyema.

A bronchopleural fistula (BF) is a life-threatening complication. Optimal management of a BF is still debated although surgery remains the preferred treatment. Usually, the fistula is a result of inadequate healing at the bronchial stump after pneumonectomy. Successful closure of a BF after pneumonectomy depends on evacuation of empyema, coverage of the suture line after fistula closure with vascularized tissue, and obliteration of the residual pleural cavity. Extrathoracic muscles and omentum are the first choice for intrathoracal transposition. We report a unique case of a cachectic female patient with a BF from the left main stem bronchus complicated with empyema following right-sided pneumonectomy. Previous surgeries excluded the use of extrathoracic muscles or only omentum. The BF could not be closed with sutures. Using a parachute technique, omentum was sutured into the fistula opening resulting in a tension-free fistula closure. A well-vascularized breast was transposed into the residual pleural cavity to obliterate dead space and to support the omentoplasty, so it would be able to withstand changes in intrathoracic pressure. The postoperative course was uneventful. Tension-free closure of a BF can be obtained by suturing well-vascularized tissue into the fistula opening using a parachute technique. Intrathoracic breast transposition could be a new option in the treatment of a BF and associated empyema in a female patient. In selected patients, a large breast can obliterate the dead space after pneumonectomy and support the omentoplasty.

Variability in peripheral rewarming after cold stress among 255 healthy Norwegian army conscripts assessed by dynamic infrared thermography.

Exposure to cold climate is an inevitable consequence of military training in Norway. Adequate peripheral microcirculation in the extremities is important to maintain temperature, and to protect against freezing cold injuries. The aim of this study was to investigate the variability in skin rewarming ability. The study subjects consisted of 260 healthy Norwegian army conscripts, following a mild cold provocation test (hands immersed in 20°C water for 1 min) using dynamic infrared thermography (DIRT). Thermal images were obtained to investigate any differences in skin rewarming ability of the hand (fingers). DIRT took place under standardised and stable study conditions. Conscripts were characterised as either slow, intermediate or rapid rewarmers. While 90% could recover, partially or completely, within 4 min to the skin temperature values before the provocation test, 10% showed a slow rewarming pattern. In the slow rewarmers, the rewarming ability was correlated with a low average temperature of the hands prior to the cooling test. The healthy young army conscripts in this study showed a large variability in their rewarming ability following a standardised mild cold provocation test.

Deformable liposomes for skin therapy with human epidermal growth factor: The effect of liposomal surface charge.

The topical administration of exogenous human epidermal growth factor (hEGF) is a promising approach for improved chronic wound therapy. To develop therapeutically superior hEGF formulation, we prepared hEGF-containing neutral (NDLs), cationic (CDLs) and anionic (ADLs) deformable liposomes (DLs), respectively, since it is expected that the liposomal surface charge can affect both the liposomal physicochemical properties, their skin penetration potential and therapeutic efficacy of liposome-associated drug. All prepared liposomes were of similar size (300-350 nm) with high hEGF load (~80% entrapment efficacy). Among the studied DLs, ADLs were found to be most promising for sustained release of hEGF, as assessed in vitro using the polyamide membrane. Ex vivo studies revealed that all DLs were excellent systems for skin therapy with hEGF and no penetration of hEGF through the full thickness human skin was detected. ADLs provided a depot exhibiting the highest hEGF retention onto the human skin surface. ADLs also revealed enhanced mitogenic activities in human fibroblasts compared to both NDLs and CDLs after 48 hrs treatment. Moreover, hEGF-containing ADLs significantly enhanced mitogenic activity in fibroblast as compared to activity of hEGF solution (positive control). Similar trends were observed in human keratinocytes after 24 hrs of treatment. We proved that the liposomal surface charge affects the therapeutic potential of hEGF-containing liposomes. hEGF-containing ADLs can be a promising nanosystem-based formulation for localized therapy of chronic wounds.

Ultrasound-guided Sympathetic Block of the Radial Artery with Botulinum Toxin to Treat Vasospasm.

Vasospastic disorders in the hand have been treated with surgical sympathectomy and recently with botulinum toxin A (BTX) injections in the palm. The purpose of this study was to evaluate if it is possible to obtain precise administration of BTX around the radial artery using a single ultrasound-guided injection. We present a novel technique using 1 single ultrasound-guided BTX injection around the radial artery to treat vasospastic symptoms. Ten patients were included in a pilot study. All patients were referred by a rheumatologist after been diagnosed with primary or secondary Raynaud. Under ultrasound guidance, BTX was injected around the radial artery and its comitant veins 3-5 cm proximal to the wrist. Ultrasound-guided injection of BTX allowed for a precise distribution of BTX into the perivascular space of the radial artery and its comitant veins. Intravascular injection could easily be excluded. One patient reported temporary reduced grip strength, most likely due to leakage of BTX to the flexor pollicis longus muscle. No other complications were registered. All patients reported reduced number of vasospastic episodes, warmer hands, and reduced pain. Ultrasound-guided injection enables precise administration of BTX in the space surrounding the radial artery and its comitant veins. This novel approach could be a promising treatment for vasospastic disorders of the hands in patients with primary and secondary Raynaud.

The Pedicled LICAP Flap Combined with a Free Abdominal Flap In Autologous Breast Reconstructions.

BACKGROUND: Previous surgery or slim body configuration can limit the size of the available abdominal flap in autologous breast reconstruction. However, redundant skin and subcutaneous tissue lateral to the mastectomy site can be utilized as the pedicled lateral intercostal artery perforator (LICAP) flap. This study evaluates the combination of a free abdominal flap and a pedicled LICAP flap to achieve increased breast size and improved cosmetic outcome. METHODS: Patients undergoing secondary autologous breast reconstruction were included in a prospective study. The combination with a LICAP flap was used for women with insufficient abdominal flap tissue in relation to the desired breast size. The authors also assessed their modification of the original lateral thoracodorsal flap design to improve the aesthetic outcome. RESULTS: In 109 patients, 121 free abdominal flaps were performed. The combination with a pedicled LICAP flap was used in 82 free abdominal flap reconstructions (68%). The LICAP flap provided additional volume and resulted in better projection and ptosis of the neo-mamma. The overall complication rate for the LICAP flaps was 26 %; all minor complications. Despite combining flaps, the majority of patients needed additional surgery to improve breast symmetry. Breast reduction of the native breast was the most common symmetrizing procedure. CONCLUSION: In selected patients with insufficient abdominal flap tissue, a combination of a free abdominal flap and a pedicled LICAP flap is a valuable option to increase breast size and cosmetic outcome. Additional symmetrizing surgery might still be necessary.

Going skin deep: A direct comparison of penetration potential of lipid-based nanovesicles on the isolated perfused human skin flap model.

Phospholipid-based nanocarriers are attractive drug carriers for improved local skin therapy. In the present study, the recently developed isolated perfused human skin flap (IPHSF) model was used to directly compare the skin penetration enhancing potential of the three commonly used nanocarriers, namely conventional liposomes (CLs), deformable liposomes (DLs) and solid lipid nanoparticles (SLNs). Two fluorescent markers, calcein (hydrophilic) or rhodamine (lipophilic), were incorporated individually in the three nanosystems. The nanocarrier size ranged between 200 and 300nm; the surface charge and entrapment efficiency for both markers were dependent on the lipid composition and the employed surfactant. Both carrier-associated markers could not penetrate the full thickness human skin, confirming their suitability for dermal drug delivery. CLs exhibited higher retention of both markers on the skin surface compared to DLs and SLNs, indicating a depo formation. DLs and SLNs enabled the deeper penetration of the two markers into the skin layers. In vitro and ex vivo skin penetration studies performed on the cellophane membrane and full thickness pig/human skin, respectively, confirmed the findings. In conclusion, efficient dermal drug delivery can be achieved by optimization of a lipid nanocarrier on the suitable skin-mimicking model to assure system's accumulation in the targeted skin layer.

The Marriage of Sartorius and Tensor Fasciae Latae in Treating Vascular Prosthetic Graft Infections.

BACKGROUND: Vascular prosthetic graft infection in the groin is associated with high morbidity and mortality. This article presents a case series on the use of 2 flaps in the treatment of this condition. METHODS: Five patients, mean age 65 years (range, 49-74 years), with significant comorbidity were treated for an exposed and infected vascular prosthetic graft in the groin with a combination of sartorius muscle (SM) flap and tensor fascia lata (TFL) myocutaneous flap after debridement and start of microbiologic culture-guided antibiotic treatment. The SM flap was used to cover the exposed graft. To obtain stable wound coverage, the SM and remaining groin defect were closed with a pedicle TFL flap. RESULTS: All flaps survived, with only 1 TFL flap suffering a small tip necrosis. All patients obtained stable wound coverage. Donor-site morbidity was minimal. During the follow-up, mean 46 months (range, 15-79 months), 1 patient had a recurrence after 15 months due to a kink in the elongated prosthetic graft that protruded through the skin alongside the SM and TFL flaps. CONCLUSIONS: The combination of SM and TFL flaps could be a new treatment option for patients who have an exposed and infected vascular prosthetic graft in the groin. This flap combination could also be used as a prophylactic procedure for those patients with a high risk to develop such a serious complication.

A new treatment for frostbite sequelae; Botulinum toxin.

Frostbite sequelae are a relevant occupational injury outcome for soldiers in arctic environments. A Caucasian male soldier suffered frostbite to both hands during a military winter exercise. He developed sensory-motor disturbances and cold hypersensitivity. Angiography and thermography revealed impaired blood flow while Quantitative Sensory Testing indicated impaired somato-sensory nerve function. Two years after the initial event, he received an off label treatment with Botulinum toxin distributed around the neurovascular bundles of each finger. After treatment, cold sensitivity was reduced while blood flow and somato-sensory nerve function improved. The successful treatment enabled the soldier to successfully pursue his career in the army.