Residual Skin Research Articles

Experience of wound treatment on extremely severe mass burn patients involved in August 2nd Kunshan factory aluminum dust explosion accident

Objective: To explore experience of wound treatment of extremely severe mass burn patients involved in August 2nd Kunshan factory aluminum dust explosion accident. Methods: On August 2nd, 2014, 98 extremely severe burn mass patients involved in August 2nd Kunshan factory aluminum dust explosion accident were admitted to 20 hospitals in China. The patients with complete medical record were enrolled in the study and divided into microskin graft group with 56 patients and Meek skin graft group with 42 patients. Split-thickness skin in area of residual skin were resected to repair wounds of patients in microskin graft group and Meek skin graft group by microskin grafting and Meek miniature skin grafting, respectively. The residual wound size on 28 days post injury and wound infection after skin grafting of patients in the two groups, and position of donor site of all patients were retrospectively analyzed. Data were processed with t test and chi-square test. Results: The size of residual wound of patients in Meek skin graft group on 28 days post injury was (59±13)% total body surface area (TBSA), which was obviously smaller than that in microskin graft group [(70±14)%TBSA, t=4.379, P<0.05]. Twenty-nine patients in microskin graft group and 11 patients in Meek skin graft group suffered from obvious wound infection after skin grafting. Wounds of patients in two groups were repaired with residual skin around wound in head, trunk, groin, armpit, and uncommon donor sites of scrotum (4 patients), vola (10 patients), and toe or finger web (8 patients). Conclusions: Meek skin graft is the first choice for wound repair of extremely severe burn mass patients, with faster wound healing, less wound infection. Uncommon donor sites of scrotum, vola, and toe or finger web can also be used for wound repair in case of lack of skin.

Cutaneous sensitivity in unilateral trans-tibial amputees.

AimTo examine tactile sensitivity in the leg and foot sole of below-knee amputees (diabetic n = 3, traumatic n = 1), and healthy control subjects (n = 4), and examine the association between sensation and balance.MethodVibration perception threshold (VPT; 3, 40, 250Hz) and monofilaments (MF) were used to examine vibration and light touch sensitivity on the intact limb, residual limb, and homologous locations on controls. A functional reach test was performed to assess functional balance.ResultsTactile sensitivity was lower for diabetic amputee subjects compared to age matched controls for both VPT and MF; which was expected due to presence of diabetic peripheral neuropathy. In contrast, the traumatic amputee participant showed increased sensitivity for VPT at 40Hz and 250Hz vibration in both the intact and residual limbs compared to controls. Amputees with lower tactile sensitivity had shorter reach distances compared to those with higher sensitivity.ConclusionChanges in tactile sensitivity in the residual limb of trans-tibial amputees may have implications for the interaction between the amputee and the prosthetic device. The decreased skin sensitivity observed in the residual limb of subjects with diabetes is of concern as changes in skin sensitivity may be important in 1) identification/prevention of excessive pressure and 2) for functional stability. Interestingly, we saw increased residual limb skin sensitivity in the individual with the traumatic amputation. Although not measured directly in the present study, this increase in tactile sensitivity may be related to cortical reorganisation, which is known to occur following amputation, and would support similar findings observed in upper limb amputees.

Salvaging the dehisced glans penis

The glans penis may show a deep groove (surgically favorable), or may appear flat with an absent sulcus (unfavorable). Glans dehiscence following hypospadias repair, especially after multiple surgeries, frequently results in a scarred, obliterated, or absent urethral plate. The glans penis appears to be flat and grooveless. This study reported on the outcome of a two-stage salvage repair for glans dehiscence in 49 consecutive patients. Retrospective chart review was performed for all patients who underwent repair for glans dehiscence following hypospadias repair. Between January 2009 and April 2015, 49 children aged 16 months to 18 years presented with glans dehiscence following hypospadias repair. The prior number of operations ranged from one to six. Eleven children had urethral fistulas, and seven had chordee. In the first stage, the flat glans was incised deeply to visualize, but spare, the corpora. Thereafter, a free graft of oral mucosa harvested either from the lower lip or cheek, or the residual preputial skin, was sutured to the glans cleft. The grafts were fenestrated, quilted in the midline, and a tie-over dressing was applied. Any fistula or chordee was repaired during the first stage. The neo-plate was tubularized 6-12 months later, and urine drainage with a catheter was maintained for 10-14 days. In 11 patients, skin flaps appeared dusky, and nitroglycerine ointment 2% was applied for 24h to enhance the blood supply of the tissues. Subsequently, six of these children received nine or ten 90-minhyperbaric oxygen therapy sessions. Following the first stage, two patients developed hypertrophy of the mucosal grafts, and one skin graft contracted. These three patients underwent revision using a second buccal mucosal graft harvested from the cheek. One recurrent fistula was closed during the second stage. Following the second stage two patients developed a urethral fistula, and the distal sutures broke down in one patient, resulting in an over-sized meatus. None developed meatal stenosis or glans dehiscence. Graft initial take and subsequent behavior were unpredictable, but the two stage approach optimized the process of take and healing. Glans dehiscence was repaired safely and successfully by developing a deep groove, with creation of a new urethral plate followed by tubularization in two stages.

Topical propranolol for infantile haemangiomas: a systematic review.

Infantile haemangiomas are the most common tumour of infancy. Whilst the majority are left untreated to involute spontaneously, residual skin changes commonly occur, particularly in superficial haemangiomas. The current first-line treatment for problematic lesions is oral propranolol; however due to the risk of systemic adverse effects, the use of off-label topical preparations has recently been investigated. Our systematic review was conducted in accordance with PRISMA guidelines. Four databases were searched to identify original articles evaluating the use of topical propranolol as the primary therapy for infantile haemangiomas. Twelve articles with a total of 597 patients and 632 haemangiomas were included. Three topical propranolol preparations were used, creams, ointments and gels and were all prepared by local pharmaceutical laboratories. The concentration of propranolol ranged from 0.5% to 5%. Treatment duration ranged from two weeks to 16.5months. Overall, 90% of lesions improved following the initiation of topical propranolol. A good or excellent response, defined as a reduction in the size of at least 50%, was seen in 59% of lesions. Earlier initiation of treatment (less than 3 months of age) was associated with improved outcomes. No systemic adverse effects were reported. Minor local reactions were seen in 1.3% of patients. Topical propranolol is safer than oral propranolol, though may be less effective. Topical propranolol may be more suitable for patients with small, superficial haemangiomas at risk of cosmetic sequelae, where the cosmetic or symptomatic impact does not warrant oral propranolol treatment.

Differential Effects of Chlorhexidine Skin Cleansing Methods on Residual Chlorhexidine Skin Concentrations and Bacterial Recovery.

BACKGROUND Bathing intensive care unit (ICU) patients with 2% chlorhexidine gluconate (CHG)-impregnated cloths decreases the risk of healthcare-associated bacteremia and multidrug-resistant organism transmission. Hospitals employ different methods of CHG bathing, and few studies have evaluated whether those methods yield comparable results. OBJECTIVE To determine whether 3 different CHG skin cleansing methods yield similar residual CHG concentrations and bacterial densities on skin. DESIGN Prospective, randomized 2-center study with blinded assessment. PARTICIPANTS AND SETTING Healthcare personnel in surgical ICUs at 2 tertiary-care teaching hospitals in Chicago, Illinois, and Boston, Massachusetts, from July 2015 to January 2016. INTERVENTION Cleansing skin of one forearm with no-rinse 2% CHG-impregnated polyester cloth (method A) versus 4% CHG liquid cleansing with rinsing on the contralateral arm, applied with either non-antiseptic-impregnated cellulose/polyester cloth (method B) or cotton washcloth dampened with sterile water (method C). RESULTS In total, 63 participants (126 forearms) received method A on 1 forearm (n=63). On the contralateral forearm, 33 participants received method B and 30 participants received method C. Immediately and 6 hours after cleansing, method A yielded the highest residual CHG concentrations (2500 µg/mL and 1250 µg/mL, respectively) and lowest bacterial densities compared to methods B or C (P<.001). CONCLUSION In healthy volunteers, cleansing with 2% CHG-impregnated cloths yielded higher residual CHG concentrations and lower bacterial densities than cleansing with 4% CHG liquid applied with either of 2 different cloth types and followed by rinsing. The relevance of these differences to clinical outcomes remains to be determined. Infect Control Hosp Epidemiol 2018;39:405-411.

Hinge Flap with Triangular Extension for Reconstruction of Pharyngocutaneous and Laryngocutaneous Fistulas.

Hinge flaps are commonly used for closure of a pharyngocutaneous fistula (PCF) or laryngocutaneous fistula. These flaps are employed to augment the wall of the pharynx or larynx, but the junction between the reconstructed and native lumens can eventually become narrow and irregular after reconstruction with standard hinge flaps. We devised a method of adding a triangular extension to the end of either or both flaps and used it to treat 3 patients. In 1 patient who developed a PCF (4 × 10 cm) after laryngectomy followed by radiotherapy, the fistula was closed with 2 hinge flaps. One flap had a caudal triangular extension. The residual skin defect was covered by a pedicled latissimus dorsi musculocutaneous flap. Another patient who developed a PCF (2.5 × 3 cm) after laryngectomy underwent 2-stage reconstruction using a buccal mucosal graft with a triangular extension, followed by 2 hinge flaps. A patient who developed an laryngocutaneous fistula (1 × 2 cm) after radiotherapy and subsequent partial laryngectomy underwent reconstruction using 2 hinge flaps, each of which had a triangular extension. The skin defect was covered by another flap. Postoperative CT or video fluoroscopic examination of swallowing showed a smooth lumen with no strictures in all 3 patients. The triangular extension of the hinge flap supplements the pharyngeal/laryngeal wall at the junction between the reconstructed and intact regions, thus avoiding postoperative stricture. Especially with PCF reconstruction, restoration of a smooth luminal surface minimizes dysphagia.

Sustained Drug Free Remission of Lupus Panniculitis with Methotrexate: A Report From Nepal

Cutaneous manifestations are second most common presenting feature of lupus. Discoid lupus erythematosus is the most common variant amongst all; lupus panniculitis being described in only 2-5% of cases. Most cases of cutaneous lupus are associated with autoantibodies and either precede or follow the systemic manifestations of lupus. There is no proven treatment for cutaneous manifestations of lupus including lupus panniculitis. Available non-randomized studies show efficacy of hydroxychoroquine in most cases, whereas methotrexate and other immunosuppressant are used in relapsing cases. We describe a case of lupus panniculitis presenting as isolated manifestation of lupus with negative autoantibody titers which responded well to methotrexate. We observed that lesions went into drug free remission in 1 year and did not recur on 1 year follow-up. There was no residual skin atrophy or scarring. Drug free remission in isolated cases of lupus panniculitis variant could be possible with timely intervention in the absence of autoantibodies. Keywords: lupus; Methotrexate; Nepal; panniculitis.

Ideal target for psoriatic arthritis? Comparison of remission and low disease activity states in a real-life cohort

BackgroundPsoriatic arthritis (PsA) recommendations state that the target of treatment should be remission or low disease activity (LDA). We used a real-life dataset to compare different potential targets.Methods250 patients with...

Continuous astaxanthin intake reduces oxidative stress and reverses age-related morphological changes of residual skin surface components in middle-aged volunteers

Oxidative stress accelerates skin aging, and dietary supplementation with antioxidants may alleviate it. Morphological analysis of the residual skin surface components (RSSCs) allows detecting age-related changes in corneocyte desquamation, microbial presence, and lipid droplet size. We hypothesized that continuous ingestion of carotenoid antioxidant astaxanthin (4 mg/d) for 4 weeks could influence RSCC morphology and evaluated RSSC samples taken from middle-aged subjects before and after this dietary intervention. The study included 31 volunteers (17 men and 14 women) over the age of 40. RSSC samples were collected from the surface of the facial skin at the beginning (day 0) and end (day 29) of the study. In addition, blood samples were taken on days 0, 15, and 29 for measuring plasma levels of malondialdehyde that allowed assessing systemic oxidative stress. The results demonstrated that plasma malondialdehyde consistently decreased during astaxanthin consumption (by 11.2% on day 15 and by 21.7% on day 29). The analysis of RSSC samples has revealed significantly decreased levels of corneocyte desquamation (P=.0075) and microbial presence (P=.0367) at the end of the study. These phenomena as well as a significant (P=.0214) increase in lipid droplet size were more strongly manifested among obese (body mass index >30 kg/m2) subjects. All described RSSC changes correspond to a shift toward characteristics of skin associated with a younger age. The results confirm our hypothesis by demonstrating that continuous astaxanthin consumption produces a strong antioxidant effect resulting in facial skin rejuvenation which is especially pronounced in obese subjects.

Role of imaging in the diagnosis of parotid infantile hemangiomas

ObjectivesTo review the clinical presentation, imaging and follow-up of parotid infantile hemangiomas (IH). MethodsOver a 15-year period, all patients with a clinical diagnosis of parotid IH were evaluated. Imaging was available in 35. The medical records, photographs, and radiology studies of these patients were reviewed. ResultsAll patients presented at less than 4 months of age (M:F, 13:21). 19 (55)% of tumors were on the left and were bilateral in 2 patients. The majority (29 patients) presented due to localized swelling or palpable mass; the remainder had a cutaneous lesion, but no palpable mass at the time of presentation. The referring diagnosis was incomplete or incorrect in 9 patients (26%).The imaging studies all demonstrated a well-defined homogeneous mass, with no abnormality of the surrounding subcutaneous fat. Sonography showed a uniformly vascular lesion with pulsatile fast-flow seen on Doppler. On MRI, the lesion was hyperintense on T2-weighted images, isointense on T1, with intense enhancement post-contrast.Oral therapy (propranolol or corticosteroids) was prescribed in 15 (45%). Follow-up in 28 patients demonstrated stability of the lesion in 11, regression in size in 11 and complete involution in 6. After involution 2 patients underwent resection of residual tissue and/or excess skin. ConclusionsTypical clinical presentation alone may be adequate to establish a diagnosis of parotid infantile hemangioma. However, in patients with no overlying cutaneous lesion, imaging can play a critical role in confirming the diagnosis. The sonographic findings are sufficiently characteristic to allow for a definitive diagnosis, obviating the need for further investigations. If diagnostic uncertainty remains or the full extent of the lesion cannot be appreciated, then MRI should be preferred over CT to avoid ionizing radiation.

Application of sebomics for the analysis of residual skin surface components to detect potential biomarkers of type-1 diabetes mellitus

Metabolic imbalance in chronic diseases such as type-1 diabetes may lead to detectable perturbations in the molecular composition of residual skin surface components (RSSC). This study compared the accumulation rate and the composition of RSSC in type-1 diabetic patients with those in matched controls in order to identify potential biomarkers of the disease. Samples of RSSC were collected from the foreheads of type-1 diabetic (n = 55) and non-diabetic (n = 58) volunteers. Samples were subsequently analysed to identify individual components (sebomic analysis). There was no significant difference in the rate of accumulation of RSSC between type-1 diabetics and controls. In terms of molecular composition, 171 RSSC components were common to both groups, 27 were more common in non-diabetics and 18 were more common in type-1 diabetic patients. Statistically significant (P < 0.05) differences between diabetic and non-diabetic volunteers were observed in the recovered amounts of one diacylglyceride (m/z 594), six triacylglycerides (m/z 726–860) and six free fatty acids (m/z 271–345). These findings indicate that sebomic analysis can identify differences in the molecular composition of RSSC components between type-1 diabetic and non-diabetic individuals. Further work is required to determine the practical utility and identity of these potential biomarkers.

Toward Novel Wearable Pyroelectric Temperature Sensor for Medical Applications

Knowledge of an amputees’ residual limb skin temperature is considered to be of particular importance as an indicator of tissue health. Temperature within the prosthetic socket typically varies over the range 25 °C to 35 °C and this warm, confined environment causes sweating which creates favourable conditions for both the growth of bacteria and an increased risk of tissue breakdown. With this in mind a wearable sensor for the real-time measurement of temperature variations at the prosthetic socket/liner interface is under development and a proof of concept prototype is presented. The sensor exploits the large pyroelectric effect present in ferroelectric lead zirconate titanate PbZr x (Ti(1– x ))O3 (PZT) and has several inherent advantages over other methods of temperature sensing. The sensing element is a low cost commercially available thick-film PZT device. Mathematical models are developed to describe the sensor immitance and response to temperature change, and both the clamped and unclamped capacitances are investigated over the range 20 °C to 40 °C. Sensor characteristics were found to be dominated by the clamped dielectric constant and operation under short-circuit conditions is found to offer a constant sensor gain over the temperature range of interest.

A case of deep infection after instrumentation in dorsal spinal surgery: the management with antibiotics and negative wound pressure without removal of fixation

Until today the role of spinal instrumentation in the presence of a wound infection has been widely discussed and recently many authors leave the hardware in place with appropriate antibiotic...

Standardized Approach to Quantitatively Measure Residual Limb Skin Health in Individuals with Lower Limb Amputation.

Objective: (1) Develop a standardized approach to quantitatively measure residual limb skin health. (2) Report reference residual limb skin health values in people with transtibial and transfemoral amputation. Approach: Residual limb health outcomes in individuals with transtibial (n = 5) and transfemoral (n = 5) amputation were compared to able-limb controls (n = 4) using noninvasive imaging (hyperspectral imaging and laser speckle flowmetry) and probe-based approaches (laser doppler flowmetry, transcutaneous oxygen, transepidermal water loss, surface electrical capacitance). Results: A standardized methodology that employs noninvasive imaging and probe-based approaches to measure residual limb skin health are described. Compared to able-limb controls, individuals with transtibial and transfemoral amputation have significantly lower transcutaneous oxygen tension, higher transepidermal water loss, and higher surface electrical capacitance in the residual limb. Innovation: Residual limb health as a critical component of prosthesis rehabilitation for individuals with lower limb amputation is understudied in part due to a lack of clinical measures. Here, we present a standardized approach to measure residual limb health in people with transtibial and transfemoral amputation. Conclusion: Technology advances in noninvasive imaging and probe-based measures are leveraged to develop a standardized approach to quantitatively measure residual limb health in individuals with lower limb loss. Compared to able-limb controls, resting residual limb physiology in people that have had transfemoral or transtibial amputation is characterized by lower transcutaneous oxygen tension and poorer skin barrier function.

889 Lemon myrtle: A new anti-seborrheic extract for multi-ethnic skins

Seborrhea is a common cosmetic issue that occurs when oversized sebaceous glands produce excessive amounts of sebum, giving the appearance of shiny and greasy skin. Sebum is made and secreted by sebaceous glands, via the differentiation and disintegration of fully mature sebocytes, a unique process termed holocrine secretion. Moreover, skin oiliness may vary according to diet, age, hot humid climates and ethnicity. Depending on new researches, ethnicity had no significant impact on level of residual skin surface components derived from sebum but, could affect sebum quality (composition and components oxidation). Convinced by the interest to act on the genesis of the sebum secretion mechanism, we have developed a new sebosuppressive agent able to modulate sebocytes differentiation, and also sebum quality. The natural Australian extract selected has been isolated from Backhousia citriodora (Lemon Myrtle leaf). Conforming its promise, Lemon myrtle extract tested on human sebocytes decrease by 32% Epithelial Membrane Antigen expression (marker of sebocyte differentiation) and so by 30% the lipid accumulation in the cytoplasm. Furthermore, two clinical studies validate Lemon Myrtle efficacy. On one hand, at 15 and 30 days, Lemon Myrtle treatment decreases significantly skin sebum content (-17% and -31% respectively) and thus surface covered by oily spots (-17% and -22% respectively). On the other hand, a sebum lipodimic analysis on ethnic volunteers (Caucasian, Asian and African-American) demonstrates that Lemon Myrtle regulates sebum composition and protects its components from oxidation. This natural extract has proven its efficiency to modulate human sebaceous terminal differentiation, characterized by cell changes, lipid droplets accumulation, nuclear degeneration and excess sebum production. Therefore, Lemon Myrtle extract is a promising sebo-regulator to act at the genesis of sebum production and to regulate sebum quality whatever the ethnicity.

Case report: The use of a urethral diverticulum to cover the penis in a hypospadias cripple

A boy presented as a hypospadias cripple, with anatomy that included a very large diverticulum and little residual external penile skin. The degree of excess skin-like tissue of the diverticulum was sufficient to enable eversion of the longitudinally incised diverticulum and formation of a urethra from the diverticular tissue at a second operation with ultimately an excellent result.

Induced pluripotent stem cells from patients with focal cortical dysplasia and refractory epilepsy.

Focal cortical dysplasia (FCD) is caused by numerous alterations, which can be divided into abnormalities of the cortical architecture and cytological variations; however, the exact etiology of FCD remains unknown. The generation of induced pluripotent stem cells (iPSCs) from the cells of patients with neurological diseases, and their subsequent tissue-specific differentiation, serves as an invaluable source for testing and studying the initial development and subsequent progression of diseases associated with the central nervous system. A total of 2 patients demonstrating seizures refractory to drug treatment, characterized as FCD Type IIb, were enrolled in the present study. Fibroblasts were isolated from residual skin fragments obtained from surgical treatment and from brain samples obtained during surgical resection. iPSCs were generated following exposure of fibroblasts to viral vectors containing POU class 5 homeobox 1 (OCT4), sex determining region Y-box 2 (SOX2), Kruppel-like factor 4 and c-MYC genes, and were characterized by immunohistochemical staining for the pluripotent markers homeobox protein NANOG, SOX2, OCT4, TRA1-60 and TRA1-81. The brain samples were tested with antibodies against protein kinase B (AKT), phosphorylated-AKT, mechanistic target of rapamycin (mTOR) and phosphorylated-mTOR. Analysis of the AKT/mTOR pathway revealed a statistically significant difference between the cerebral tissues of the two patients, which were of different ages (45 and 12 years old). Clones with the morphological features of embryonic cells were detected on the 13th day and were characterized following three subcultures. The positive staining characteristics of the embryonic cells confirmed the successful generation of iPSCs derived from the patients' fibroblasts. Therefore, the present study presents a method to obtain a useful cellular source that may help to understand embryonic brain development associated with FCD.

Thermal Assessment for Prostheses: State-of-the-Art Review

Hundreds of young people have had limbs amputated after being wounded by civil wars, explosions or gunshots. Heat and perspiration within a prosthetic socket are the most common side effects of reduced quality life for prosthesis. Besides, the environment between liner and skin is an ideal host of residual limb skin problems such as contact dermatitis and bacterial infections. It is important to minimize the limiting heat transfer to improve amputee safety and comfort. Usually, when there is a skin problem, the treatment requires the amputee not to wear his/her prosthesis for an extended period of time. This functional loss can adversely affect the amputee’s physical, mental and emotional well-being. This work aims to highlight a number of important issues concerning the effect of thermal conditions on prosthetics to shed light on new design methods for prosthetics.

Morphological Characteristics of Residual Skin Surface Components Collected from the Surface of Facial Skin in Women of Different Age.

BackgroundProblems of skin aging and its prevention currently attract increasing attention with the growth of human life expectancy. The morphology of the stratum corneum (SC) is well known, but investigation of age-related changes of its structure is difficult in the absence of non-invasive sampling methods. The residual skin surface components (RSSC) that overlay the SC can be easily collected non-invasively.ObjectiveThe aim of this study was to examine morphology of RSSC samples collected from the surface of facial skin of healthy female volunteers of different age.MethodsRSSC samples were non-invasively collected from 53 adult female volunteers (22 aged in the range 18∼25 years and 31 aged in the range 50∼73 years). The samples were analysed microscopically.ResultsDistinct age-related changes were determined for lipid droplet size, corneocyte desquamation level and lipid crystal count. There was a significant (p=0.0006) decrease in lipid droplet size among older women. Similarly, significantly (p=0.0401) lower lipid crystal numbers were present in the older group. Conversely, corneocyte desquamation was significantly higher (p=0.0007) in older women. No age-related difference in microbial presence in the RSSC could be detected. Result patterns were generally similar to those previously found in male volunteers; however gender-related differences in the absolute values were revealed.ConclusionNon-invasively collected RSSC samples allow identifying age-related changes on facial skin surface. The results of this study highlight gender-dependence of distinct elements of age-associated impairment of epidermal barrier and can be employed for developing new approaches to prevent changes associated with skin aging.

Results from Phase 2 Trial Ongoing Expansion Stage of SL-401 in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Background: SL-401 is a targeted therapy directed to the interleukin-3 receptor (CD123), a target overexpressed on blastic plasmacytoid dendritic cell neoplasm (BPDCN) and other hematologic malignancies. BPDCN is an aggressive hematologic malignancy of unmet medical need that often presents in bone marrow and skin, and may also involve lymph nodes and viscera. Long-term outcomes after treatment with chemotherapy have been very poor, with median overall survival from diagnosis of ~12 months, highlighting the need for novel therapies. Results from the Phase 2 trial of SL-401 in patients with BPDCN are reported here.Methods:This multicenter, single-arm Phase 2 trial of patients with BPDCN includes a lead-in (stage 1) and expansion (stage 2). In stage 1, patients with BPDCN or relapsed or refractory (r/r) AML received SL-401 as a daily IV infusion at 7, 9, 12, or 16 ug/kg/day for days 1-5 of a 21 day cycle. In stage 2, patients with BPDCN receive SL-401 at the dose determined in stage 1.Results: As of 7/25/16, 29 patients with BPDCN have received SL-401, including 16 first-line and 10 relapsed/refractory (r/r) adults and 3 pediatric patients (under compassionate use). The 26 adult patients (9+17 in stages 1&2) received SL-401 at 7 ug/kg (n=3 [stage 1]) or 12 ug/kg (n=23 [6+17 in stages 1&2]). The median adult age was 69 years (range: 29-82 years). In stage 1, 12 ug/kg was the highest tested dose for BPDCN; MTD was not reached in BPDCN. Results in AML (r/r) patients will be reported separately. The most common treatment-related AEs, all grades, were transient transaminase elevation (54%) and hypoalbuminemia (38%). Transient thrombocytopenia was also noted (19%). The most common ≥ Grade 3 treatment-related AEs were transient transaminase elevation (42%) and thrombocytopenia (19%). Two stage 1 patients developed capillary leak syndrome (CLS): gr 5 (7 ug/kg) and gr 4 (12 ug/kg). Safety precautions, including monitoring of albumin levels and body weight, were successfully implemented to minimize risk of severe CLS, which has not occurred in patients with BPDCN since adoption. Twenty-one of 26 adult patients were evaluable for response (response assessment from 3 recently treated patients are pending; 1 patient was discontinued for as yet unspecified reasons; and 1 patient treated at 7 ug/kg was not evaluable for response due to AE); median follow-up for evaluable patients was 6.9 months (range: 0.6-17.6 months). An 86% (18/21) ORR was observed in evaluable adult BPDCN patients. ORR in evaluable patients was 100% (14/14) in first-line and 57% (4/7) in r/r BPDCN. Of these, 92% (11/12) of first-line patients treated at 12 ug/kg had a CR (n=8) or clinical CR (CRc: a CR in non-skin organs with gross reduction in cutaneous lesions and residual microscopic skin disease) (n=3). 75% (9/12) of these patients remain progression free for 3+ to 16+ months (ongoing), including 4 patients who remain on SL-401 in remission (for 3+ to 12+ months [up to 16+ cycles], ongoing) and 5 additional patients who experienced a major response on SL-401 (3 CR, 1 CRc, 1 PR) and were then successfully bridged to stem cell transplant (SCT; 3 auto-SCT and 2 allo-SCT) and all remain progression free for 3+ to 16+months (ongoing) since first SL-401 dose. Notably, a patient with r/r BPDCN was recently bridged to allo-SCT following CRc on SL-401.Conclusions: SL-401 demonstrates robust single agent activity in BPDCN, including 86% ORR in all-lines, with multiple CRs, in evaluable patients. Six patients, including 1 r/r patient, have proceeded to SCT after achieving a major response from SL-401, and an additional 7 patients remain on SL-401 for up to 12+ months, ongoing. The SL-401 side effect profile remains manageable, and no unexpected AEs have emerged with increased treatment duration, drug exposure, and patient enrollment. Response duration, progression-free and overall survival data continue to be encouraging and updated data will be presented. Clinical trial information: NCT02113982. DisclosuresLane:N-of-1: Consultancy; Stemline Therapeutics: Research Funding. Sweet:Ariad: Consultancy, Speakers Bureau; Incyte Corporation: Research Funding; Pfizer: Speakers Bureau; Karyopharm: Honoraria, Research Funding; Novartis: Consultancy, Speakers Bureau. Stein:Seattle Genetics: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Stemline Therapeutics: Consultancy, Research Funding; Argios: Research Funding; Celgene: Research Funding. Wang:Immunogen: Research Funding; Incyte: Speakers Bureau. Chen:Stemline Therapeutics, Inc.: Employment, Equity Ownership. Shemesh:Stemline Therapeutics: Employment, Equity Ownership. McDonald:Stemline Therapeutics: Employment, Equity Ownership. Brooks:Stemline Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties. Lancet:Quantum First: Consultancy; Pfizer: Research Funding; Seattle Genetics: Consultancy; Novartis: Consultancy; Biopath Holdings: Consultancy; ERYtech: Consultancy; Karyopharm: Consultancy; Baxalta: Consultancy; Kalo Bios: Consultancy; Celgene: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Boehringer-Ingelheim: Consultancy; Amgen: Consultancy. Kantarjian:Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; ARIAD: Research Funding; Pfizer Inc: Research Funding; Delta-Fly Pharma: Research Funding; Novartis: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding.