Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma.

Medulloblastoma is the most common pediatric malignant brain tumor. Although current therapies improve survival, these regimens are highly toxic and are associated with significant morbidity. Here, we report that placental growth factor (PlGF) is expressed in the majority of medulloblastomas, independent of their subtype. Moreover, high expression of PlGF receptor neuropilin 1 (Nrp1) correlates with poor overall survival in patients. We demonstrate that PlGF and Nrp1 are required for the growth and spread of medulloblastoma: PlGF/Nrp1 blockade results in direct antitumor effects in vivo, resulting in medulloblastoma regression, decreased metastasis, and increased mouse survival. We reveal that PlGF is produced in the cerebellar stroma via tumor-derived Sonic hedgehog (Shh) and show that PlGF acts through Nrp1-and not vascular endothelial growth factor receptor 1-to promote tumor cell survival. This critical tumor-stroma interaction-mediated by Shh, PlGF, and Nrp1 across medulloblastoma subtypes-supports the development of therapies targeting PlGF/Nrp1 pathway.

The Psychosocial Impact of Atopic Dermatitis.

Atopic dermatitis is a chronic skin condition that has significant psychosocial and quality-of-life impact. The condition causes physical discomfort, emotional distress, embarrassment, social stigma, and daily activity limitation. In an effort to assess these aspects of disease burden, quality-of-life measurement tools were developed. Through use of these tools, we have expanded our knowledge of the psychosocial and quality-of-life burden of this condition. A variety of quality of assessment tools exist, yet there is no consensus on which tool is best suited to assess the quality-of-life impact of atopic dermatitis. Research studies assessing quality-of-life in atopic dermatitis patients utilize a variety of quality-of-life measurement tools; this complicates comparisons across research studies. Though comparison across studies is difficult, the data echoes tremendous overall burden of disease, especially pertaining to psychosocial status and life quality.

State-of-the-Art Lymphedema Surgery Treatment Program.

The purpose of this article is to describe the multidisciplinary lymphedema surgery treatment program at Washington University in St. Louis. In this article, we discuss our collaboration with colleagues in medicine and therapy for conservative management and lymphedema staging. We describe our preferred imaging modalities for diagnosis, staging, and surgical treatment. Finally, we provide an overview of the surgical procedures we perform and our surgical treatment algorithm.

The Effect of Enhanced Recovery after Surgery Pathway Implementation on Abdominal-Based Microvascular Breast Reconstruction.

BACKGROUND: Although Enhanced Recovery after Surgery (ERAS) pathways are becoming the standard of care in microvascular breast reconstruction, evidence supporting their use is limited or based on small sample sizes. We hypothesized that improvements in postoperative outcomes would persist when examining the largest cohort of patients undergoing abdominal-based microvascular breast reconstruction, to date. MATERIALS AND METHODS: Data were retrospectively reviewed for 276 consecutive patients who underwent abdominal-based free flap breast reconstruction before and after ERAS implementation (pre-ERAS, n = 138 patients; post-ERAS, n = 138 patients). Primary outcomes were postoperative opioid use measured in oral morphine equivalents (OMEs), median hospital length of stay (LOS) in days, and incidence of postoperative complications. RESULTS: Postoperative opioid requirements were significantly lower in the post-ERAS cohort compared with the pre-ERAS cohort (57.3 OME, [interquartile range 20.0-115.5] versus 297.3 OME [interquartile range 138.6-437.7], P < 0.0001). There was no significant difference in hospital LOS when controlling for variables that differed between the groups. In addition, there were no differences in the rate of postoperative complications, return to operating room, or readmission after ERAS pathway implementation. CONCLUSIONS: ERAS improves specific aspects of recovery for patients undergoing microvascular breast reconstruction, most notably postoperative opioid use. Patient selection and a shift toward less invasive procedures may explain a nonsignificant impact on hospital LOS.

The Utility of Polyether-Ether-Ketone Implants Adjacent to Sinus Cavities After Craniofacial Trauma.

PURPOSE: Polyether-ether-ketone (PEEK) implants have become increasingly popular for use in reconstructive procedures. It is imperative to understand the consequences of using this biomaterial in anatomic sites that can pose a risk of infection. Specifically, the use of PEEK in paranasal sinus cavity reconstruction is not well documented. This study examined postoperative complications, namely surgical site infection and implant loss, in patients who underwent paranasal sinus cavity reconstruction using PEEK implants. MATERIALS AND METHODS: This study is a single-center case series. Patients who underwent craniomaxillofacial reconstruction with a custom-made PEEK implant in intimate contact with a functional paranasal sinus from June 2013 to May 2017 were included. Baseline characteristics and preoperative and postoperative variables were collected by retrospective chart review. RESULTS: Eight patients were included in this study. Average patient age was 45.75 ± 19.36 years. Average follow-up duration was 300 ± 263 days. Mean operative time for PEEK implantation was 214.13 ± 66.03 minutes. Implant size ranged from 5 to nearly 100 cm2. No patients were diagnosed with acute or chronic sinusitis postoperatively. One patient underwent explantation of his PEEK implant secondary to breakdown of overlying skin that separated from the site of the frontal sinus because of coagulase-negative Staphylococcus epidermis infection. CONCLUSIONS: Literature review indicates that this is the largest case series reported to date documenting the use of PEEK implants in reconstruction of the region of the paranasal sinuses. Specific biologic, or alloplastic, barriers outside the formation of native scar tissue or regional fasciocutaneous tissues at the sites of reconstruction were not used in these reconstructions, although consideration for placement of these barriers can be at the discretion of the operative surgeon. The authors conclude that PEEK implants can be used in complex craniomaxillofacial reconstructive procedures to achieve near anatomic reconstruction not easily attainable through conventional means. Defects that involve the paranasal sinus cavities with a functional ostium or obliterated sinus cavity can be reconstructed with PEEK implants without increasing the risk of infection and need for explantation. Long-term follow-up and continued outcome results of this treatment modality will be necessary to verify its clinical usefulness in the future.

The Psychosocial Impact of Atopic Dermatitis.

Atopic dermatitis is a chronic skin condition which has significant psychosocial and quality of life impact. The condition causes physical discomfort, emotional distress, embarrassment, social stigma and daily activity limitation. In an effort to assess these aspects of disease burden, quality of life measurement tools were developed. Through use of these tools, we have expanded our knowledge of the psychosocial and quality of life burden of this condition. A variety of quality of life assessment tools exist, yet there is no consensus on which tool is best suited to assess the quality of life impact of atopic dermatitis. Research studies assessing quality of life in atopic dermatitis patients utilize a variety of quality of life measurement tools; this complicates comparisons across research studies. Though comparison across studies is difficult, the data echoes tremendous overall burden of disease, especially pertaining to psychosocial status and life quality.

P75 neurotrophin receptor expression in squamous cell carcinoma.

P75 neurotrophin receptor (p75) is a transmembrane protein in the tumor necrosis receptor superfamily useful for the diagnosis of desmoplastic melanomas, desmoplastic trichoepitheliomas, and more recently used for detecting perineural invasion in oral and esophageal squamous cell carcinomas (SCCs). P75 staining in cutaneous SCCs is more controversial with initial staining reported as negative but more recent reports indicating that it may be a useful immunohistochemical marker of perineural invasion. A poorly differentiated pleomorphic epithelioid cell proliferation, which had strong p75 staining in the periphery of epithelioid cell nests, is being reported. Both low and high molecular weight keratins were positive and SOX10, S100, and HMB-45 staining were negative, consistent with a poorly differentiated SCC. To our knowledge, this pattern has not yet been reported and most likely reflects reiteration of the basal layer epithelium, which normally stains positively for p75. Reports of p75 staining in cutaneous SCCs are still limited, and a larger scale study may prove useful in determining its role as a marker for perineural invasion.

Delayed implant augmentation of breast free flaps.

BACKGROUND: Two commonly used breast reconstruction techniques are (1) implant-based and (2) abdominal tissue-based procedures. When the two modalities are combined, the result is a unique construct that shares advantages and disadvantages of both approaches. Combining breast flaps and implants has been reported, yet the specific techniques associated with a reliable outcome remain unclear. MATERIALS AND METHODS: Between July 2010 and 2014, a review of all patients who underwent delayed implant augmentation of a breast free flap reconstruction by the senior author was performed. Data were collected on patient characteristics, implants used, timing of reconstruction, and position of implant relative to the flap. RESULTS: During the study period, 101 patients underwent breast reconstruction with 161 abdominal free flaps. Of these, 12 patients (12%) and 17 flaps (11%) had delayed implant augmentation. Of the 17 augmented flaps, 12 had expanders placed before final implant placement. Eleven implants were placed in the subflap position and 6 in the subpectoralis major position. The mean final implant size was 296.5 mL (range, 125-510 mL). At a mean follow-up of 17.1 months, there was one expander removed before complete expansion for impending extrusion and one silicone gel implant revision for malposition. CONCLUSION: The results of delayed breast flap implant augmentation can be reliable and generate results that may not be obtainable with flaps or implants alone. Admittedly, the addition of an implant to a flap reconstruction exposes the patient to implant-related complications that would otherwise have been circumvented by a pure autologous reconstruction.

Perineal hernia as a sequela of anal reconstruction surgeries in perianal Crohn's disease.

Perineal hernia is a rare complication of pelvic surgeries that can occur in patients with perianal Crohn's disease (pCD) as a long-term outcome of surgeries for complex fistula treatment. We present a case of a symptomatic pCD male patient with multiple perianal surgeries who presents with anal pain, diarrhea, and discharge. Magnetic resonance imaging showed a perineal hernia in the ischioanal fossa violating the convergence of the left external sphincter complex. The hernia was treated with an open primary hernia repair via the perineal approach. It recurred after 3 months, and the patient underwent secondary hernia repair with gracilis muscle interposition and mesh placement. Unfortunately, this was complicated by superficial skin dehiscence and mesh extrusion, but the flap remained viable and the hernia repair was intact. Incidence, symptoms, risk factors, imaging findings, and management of perineal hernias are reviewed.

Rapid Implementation of a 3-Dimensional-Printed Patient-Specific Titanium Sacrum Implant for Severe Neuropathic Spinal Arthropathy and Guide to Compassionate US Regulatory Approval.

BACKGROUND AND OBJECTIVE: Rapid design and production of patient-specific 3-dimensional-printed implants (3DPIs) present a novel opportunity to restore the biomechanically demanding integrity of the lumbopelvic junction. We present a unique case of a 61-year-old patient with severe neuropathic spinal arthropathy (Charcot spine) who initially underwent a T4-to-sacrum spinal fusion. Massive bone destruction led to dissociation of his upper body from his pelvis and legs. Reconstruction of the spinopelvic continuity was planned with the aid of a personalized lumbosacral 3DPI. METHOD: Using high-resolution computed tomography scans, the custom 3DPI was made using additive titanium manufacturing. The unique 3DPI consisted of (1) a sacral platform with iliac screws, (2) modular corpectomy device with rigid connection to the sacral platform, and (3) anterior plate connection with screws for proximal fixation. The procedures to obtain compassionate use Food and Drug Administration approval were followed. The patient underwent debridement of a chronically open wound before undertaking the 3-stage reconstructive procedure. The custom 3DPI and additional instrumentation were inserted as part of a salvage rebuilding procedure. RESULTS: The chronology of the rapid implementation of the personalized sacral 3DPI from decision, design, manufacturing, Food and Drug Administration approval, and surgical execution lasted 28 days. The prosthesis was positioned in the defect according to the expected anatomic planes and secured using a screw-rod system and a vascularized fibular bone strut graft. The prosthesis provided an ideal repair of the lumbosacral junction and pelvic ring by merging spinal pelvic fixation, posterior pelvic ring fixation, and anterior spinal column fixation. CONCLUSION: To the best of our knowledge, this is the first case of a multilevel lumbar, sacral, and sacropelvic neuropathic (Charcot) spine reconstruction using a 3DPI sacral prosthesis. As the prevalence of severe spine deformities continues to increase, adoption of 3DPIs is becoming more relevant to offer personalized treatment for complex deformities.

Histologic features of nail cosmetics.

Nail cosmetics and adornments are widely used in today's society. However, their histologic features are not well characterized. Routine histologic examination and polarization of nail plate specimens in our academic dermatopathology practice at the Hospital of the University of Pennsylvania revealed 3 distinct histologic patterns of nail cosmetics: a hyperpigmented pattern with diffuse fine granular material, a layered pattern with a single linear band of polarizable material, and a hyperpigmented pattern with larger granules containing flecks of polarizable material. In our experience, submitting clinicians rarely indicate the patient's use of nail polish or other enhancements. Recognition of the histologic features of nail cosmetics is important to prevent confusion with dermatoses affecting the nail unit, and it will help dermatopathologists render more accurate diagnoses.

Onychophagia-induced longitudinal melanonychia.

An otherwise-healthy 13-year-old girl with previously normal nails developed longitudinal pigmented bands on multiple fingernails. Physical examination revealed faintly pigmented bands on multiple fingernails and on the left fifth toenail. We believed that the cause of the pigmented bands was onychophagia-induced longitudinal melanonychia, a rare phenomenon, which emphasizes the need for dermatologists to question patients with melanonychia about their nail biting habits because they may not be forthcoming with this information.

Use of mobile learning by resident physicians in Botswana.

With the growth of mobile health in recent years, learning through the use of mobile devices (mobile learning [mLearning]) has gained recognition as a potential method for increasing healthcare providers' access to medical information and resources in resource-limited settings. In partnership with the University of Botswana School of Medicine (SOM), we have been exploring the role of smartphone-based mLearning with resident (physicians in specialty training) education. The SOM, which admitted its first class of medical students and residents in 2009, is committed to providing high-level on-site educational resources for resident physicians, even when practicing in remote locations. Seven residents were trained to use an Android-based myTouch 3G smartphone equipped with data-enabled subscriber identity module (SIM) cards and built-in camera. Phones contained locally loaded point-of-care and drug information applications, a telemedicine application that allows for the submission of cases to local mentors, and e-mail/Web access. Surveys were administered at 4 weeks and 8 weeks following distribution of phones. We found that smartphones loaded with point-of-care tools are effectively utilized by resident physicians in resource-limited settings, both for accessing point-of-care medical information at the bedside and engaging in self-directed learning at home.

Immediate Dental Implant Placement in the Oncologic Setting: A Conceptual Framework.

Historically, immediate dental implants have been reserved for patients with benign disease, with full dental rehabilitation rarely being accomplished in the oncologic setting due to concerns related to implant survival, flap compromise, and delay in initiation of adjuvant therapy. Recent developments in technology have made immediate dental implants using virtual surgical planning safe and reliable. At Memorial Sloan Kettering Cancer Center, we have implemented a workflow for immediate dental implant placement in the oncologic patient population that has become a routine part of maxillary and mandibular reconstruction. This approach begins with a multidisciplinary virtual surgical planning session and custom dental splints to be used for cutting and inset guides. Dental implants are placed intraoperatively at the time of tumor resection and reconstruction with the fibula flap. A temporary prosthesis, which can be worn during radiation therapy, is placed following a vestibuloplasty, approximately 4-6 weeks after the initial reconstruction. After the completion of radiation therapy and the resolution of edema, a permanent prosthesis is placed. When critically evaluating our experience, we have found that patients undergoing immediate dental implant placement have higher rates of implant survival and no delay in adjuvant therapy. The protocol described here in detail has successfully expanded the indications for immediate dental rehabilitation in the oncologic patient population.

Does Realism Matter? A Randomized Controlled Trial Comparing Models for Medical Student Suture Education.

BACKGROUND: We hypothesized that medical students trained in suturing using high-fidelity models (cadaveric tissue) would demonstrate greater proficiency when compared with those trained using low-fidelity models (synthetic tissue). METHODS: Forty-three medical students were randomized into 2 groups. Group 1 consisted of students taught to perform simple interrupted sutures using synthetic tissue, and group 2 consisted of those taught using human cadaveric tissue. Suturing proficiency was measured pre- and postinstruction using the Global Rating Scale and by measuring suture accuracy. Perceived confidence in suturing was measured on a scale of 0-100. RESULTS: Perceived confidence was measured as an average of 8.26 out of 100 pretraining and significantly improved after training (56.91 out of 100); however, there was no significant difference when comparing confidence between groups posttraining (57.65 cadaveric versus 56.05 synthetic; P = 0.78), nor in the measured confidence change pre- and posttraining (P = 0.53). Posttraining, participants displayed a significant improvement in the number of adequately placed sutures; however, there was no significant difference posttraining when comparing groups (2.43 cadaveric versus 2.75 synthetic; P = 0.48). The change in adequate suture placement pre- and posttraining did not reach statistical significance between groups (P = 0.27). After instruction, participants demonstrated a significant improvement in total suture performance scores; however, there was no significant difference when comparing groups (30.04 cadaveric versus 29.80 synthetic; P = 0.90), nor in the total change pre- and posttraining (P = 0.74). CONCLUSIONS: Training medium fidelity (tissue versus synthetic) does not significantly influence a student's overall suturing performance. However, formal instruction significantly improves objective competence and perceived confidence. Regardless of the model, surgical departments should emphasize medical student exposure to basic surgical skills education.

Occurrence of Symptomatic Hypotension in Patients Undergoing Breast Free Flaps: Is Enhanced Recovery after Surgery to Blame?

BACKGROUND: Enhanced recovery after surgery (ERAS) initiatives improve postoperative function and expedite recovery, leading to a decrease in length of stay. The authors noted a high rate of postoperative symptomatic hypotension in patients undergoing abdominal free flap breast reconstruction and wished to explore this observation. METHODS: Subjects undergoing abdominal free flap breast reconstruction at the authors' institution from 2013 to 2017 were identified. The ERAS protocol was initiated in 2015 at the authors' hospital; thus, 99 patients underwent traditional management and 138 patients underwent ERAS management. Demographics and perioperative data were collected and analyzed. Postoperative symptomatic hypotension was defined as mean arterial pressure below 80 percent of baseline with symptoms requiring evaluation. RESULTS: A significantly higher rate of postoperative symptomatic hypotension was observed in the ERAS cohort compared with the traditional management cohort (4 percent versus 22 percent; p < 0.0001). Patients in the ERAS cohort received significantly less intraoperative intravenous fluid (4467 ml versus 3505 ml; p < 0.0001) and had a significantly increased amount of intraoperative time spent with low blood pressure (22 percent versus 32 percent; p =0.002). Postoperatively, the ERAS cohort had significantly lower heart rate (77 beats per minute versus 88 beats per minute; p < 0.0001) and mean arterial pressure (71 mmHg versus 78 mmHg; p < 0.0001), with no difference in urine output or adverse events. CONCLUSIONS: The authors report that ERAS implementation in abdominal free flap breast reconstruction may result in a unique physiologic state with low mean arterial pressure, low heart rate, and normal urine output, resulting in postoperative symptomatic hypotension. Awareness of this early postoperative finding can help better direct fluid resuscitation and prevent episodes of symptomatic hypotension. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Dermatitis artefacta.

Dermatitis artefacta, also known as factitial dermatitis, is a condition whereby self-induced skin damage is the means used to satisfy a conscious or unconscious desire to assume the sick role. It is particularly common in women and in those with an underlying psychiatric diagnosis or external stress. The diagnosis is one of exclusion, and it is often difficult to confirm, with patients rarely admitting their role in the creation of their lesions. Treatment can be challenging, and management should adopt a multidisciplinary team approach composed of dermatologists and mental health professionals. We present a literature review of dermatitis artefacta, highlighted by a case report of a patient with bilateral ulcerations to the legs, which after thorough investigation represented dermatitis artefacta.