Phenotype, cancer risk, and surveillance in Beckwith-Wiedemann syndrome depending on molecular genetic subgroups.

Patients with Beckwith-Wiedemann syndrome (BWS) have an increased risk to develop cancer in childhood, especially Wilms tumor and hepatoblastoma. The risk varies depending on the cause of BWS. We obtained clinical and molecular data in our cohort of children with BWS, including tumor occurrences, and correlated phenotype and genotype. We obtained similar data from larger cohorts reported in the literature. Phenotype, genotype and tumor occurrence were available in 229 of our own patients. Minor differences in phenotype existed depending on genotype/epigenotype, similar to earlier studies. By adding patients from the literature, we obtained data on genotype and tumor occurrence of in total 1,971 BWS patients. Tumor risks were highest in the IC1 (H19/IGF2:IG-DMR) hypermethylation subgroup (28%) and pUPD subgroup (16%) and were lower in the KCNQ1OT1:TSS-DMR (IC2) subgroup (2.6%), CDKN1C (6.9%) subgroup, and the group in whom no molecular defect was detectable (6.7%). Wilms tumors (median age 24 months) were frequent in the IC1 (24%) and pUPD (7.9%) subgroups. Hepatoblastoma occurred mostly in the pUPD (3.5%) and IC2 (0.7%) subgroups, never in the IC1 and CDKN1C subgroups, and always before 30 months of age. In the CDKN1C subgroup 2.8% of patients developed neuroblastoma. We conclude tumor risks in BWS differ markedly depending on molecular background. We propose a differentiated surveillance protocol, based on tumor risks in the various molecular subgroups causing BWS. © 2016 Wiley Periodicals, Inc.

Taste and speech following surgical tongue reduction in children with Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder in which macroglossia is one of the main signs. We investigated the long-term outcome of tongue surgery reduction (TRS) on taste and speech in patients with BWS who were more than 5 years of age and had undergone surgical anterior wedge resection of the tongue. A questionnaire was used to assess medical history and to determine some aspects of speech, taste, psychological well-being, and degree of satisfaction with regard to TRS and tongue mobility. Speech sound error pattern and degree of intelligibility were measured by a speech therapist, and taste was assessed using a validated test. The degree of both intelligibility and satisfaction with the surgery was high. There were some speech errors; especially the interdental 's', addental 't', and addental 'd' were more noticed. We conclude that anterior wedge resection is an effective technique to treat macroglossia in children with BWS, and that it has no long-term consequences for intelligibility and taste perception and only limited consequences for speech.

Cognitive Impairment and Electroconvulsive Therapy in Geriatric Depression, What Could be the Role of Rivastigmine? A Case Series.

Electroconvulsive therapy (ECT), albeit highly effective in treating depression, is frequently associated with cognitive impairment, either temporary or more persistent. Especially in older patients, who generally respond even better, serious cognitive impairment during the course of ECT may lead to premature termination of ECT. Treatment of this cognitive impairment is of utmost importance. In this case series report, we present the effect of rivastigmine, an acetylcholinesterase inhibitor, on cognitive impairment in three older, severely depressed patients during or after a course of ECT. An improvement of cognitive functioning, in particular a decline of confusional symptoms, was observed in two patients with structural brain alterations associated with aging. In the other patient, who suffered primarily from amnesia, no effect of rivastigmine was observed. These preliminary results emphasize the need for detailed profiling of cognitive impairment when developing a research design to study the potential benefits of rivastigmine in the prevention or treatment of cognitive impairment in severely depressed patients treated with ECT.

Treatment of Basal Cell Carcinoma Using a One-Stop-Shop With Reflectance Confocal Microscopy: Study Design and Protocol of a Randomized Controlled Multicenter Trial.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer diagnosed in white populations worldwide. The rising incidence of BCC is becoming a major worldwide public health problem. Therefore, there is a need for more efficient management. OBJECTIVE: The aim of this research is to assess the efficacy and safety of a one-stop-shop (OSS) concept, using real-time in vivo reflectance confocal microscopy (RCM) (Vivascope 1500; Lucid Technologies, Henrietta, NY, USA) as a diagnostic tool, prior to surgical management of new primary BCCs. METHODS: This is a prospective non-inferiority multi-center RCT designed to compare the "OSS concept using RCM" to current standards of care in diagnosing and treating clinically suspected BCC. Patients ≥ 18 years attending our outpatient clinic at the Department of Dermatology, Academic Medical Center, University of Amsterdam, and the Department of Dermatology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (Amsterdam, The Netherlands) with a clinically suspected new primary BCC lesion will be considered for enrollment using predefined inclusion and exclusion criteria, and will be randomly allocated to the experimental or control group. The main outcome parameter is the assessment of incomplete surgical excision margins on the final pathology report of confirmed BCC lesions (either by punch biopsy or RCM imaging). Other outcome measures include diagnostic accuracy (sensitivity and specificity) of RCM for diagnosing BCC and dividing between subtypes, and throughput time. Patient satisfaction data will be collected postoperatively after 3 months during routine follow-up. RESULTS: This research is investigator-initiated and received ethics approval. Patient recruitment started in February 2015, and we expect all study-related activities to be completed by fall 2015. CONCLUSIONS: This RCT is the first to examine an OSS concept using RCM for diagnosing and treating clinically suspected BCC lesions. Results of this research are expected to have applications in evidence-based practice for the increasing number of patients suffering from BCC and possibly lead to a more efficient disease management strategy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02285790; https://clinicaltrial.gov/ct2/show/NCT02285790 (Archived by WebCite at http://www.webcitation.org/6b2LfDKWu).

Complications After Facial Injections With Permanent Fillers: Important Limitations and Considerations of MRI Evaluation.

BACKGROUND: Soft-tissue fillers have become more prevalent for facial augmentation in the last 2 decades, even though complications of permanent fillers can be challenging to treat. An investigative imaging tool could aid in assessing the nature and extent of these complications when clinical findings are ambiguous. OBJECTIVES: The authors analyzed the value of magnetic resonance imaging (MRI) in the assessment of delayed-onset complications after injection of patients with permanent fillers. METHODS: Thirty-two patients with complications related to facial fillers were evaluated in this prospective cohort study. Their medical history was documented, and MRI was conducted before treatment of the complications. Radiologists were informed of the injection sites but were blinded to the results of other clinical evaluations. Levels of agreement between clinical and radiologic findings were calculated with the Jaccard similarity coefficient. RESULTS: A total of 107 site-specific clinicoradiologic evaluations were analyzed. The level of agreement was assessed as strong for deposits without complications and noninflammatory nodules (combined 85%), moderate for abscesses (60%), fair for low-grade inflammations (32%), and slight for migrations (9%). Results from the MRI examinations aided in subsequent treatment decisions in 11% of cases. CONCLUSIONS: Study results show that MRI may be useful for diagnosing complications associated with fillers that have migratory potential, for depiction of the extent of deposits before treatment, and for follow-up of low-grade inflammation and abscesses after surgery. LEVEL OF EVIDENCE: 3.

Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood.

The Beckwith-Wiedemann syndrome is caused by disturbed imprinting of genes at 11p15.5. Routine diagnostic testing for Beckwith-Wiedemann syndrome (BWS) includes methylation analysis of the imprinting centers ICR1 and ICR2 in DNA extracted from lymphocytes. In approximately 15% of BWS patients the diagnosis cannot be molecularly confirmed. In this study we determined the methylation status in resected tongue tissue of 11 BWS patients and compared this to the genetic defects found by routine diagnostic screening of blood lymphocytes. In all three patients with normal methylation levels in blood, aberrant methylation patterns were found in tongue tissue. In two patients a UPD was detected and the third case had hypermethylation of ICR1. This result shows that tissue specific mosaic (epi)genetic changes, not present in blood, is the underlying defect in at least a subset of BWS patients without a molecular diagnosis after standard genetic testing.

Delayed-onset complications of facial soft tissue augmentation with permanent fillers in 85 patients.

OBJECTIVE: To evaluate factors influencing the onset and type of adverse events in patients injected with permanent fillers in the face and to propose a therapeutic strategy for these complications. METHODS: A prospectively attained series of 85 patients with delayed-onset complications after facial injection with permanent fillers underwent clinical follow-up and treatment of the complications. RESULTS: Lag times until onset and type of delayed-onset complication varied according to filler material. In 28% (n = 24) of the cases, patients reported the onset of complications after dental procedures, additional injections with fillers, or other invasive treatments in the facial area. Forty-eight (57%) patients required invasive treatment. Abscess formation was significantly more frequent in patients with human immunodeficiency virus infection and facial lipoatrophy (p = .001). CONCLUSION: The intrinsic characteristics of the injected filler and the immune status of the patient play important roles in the diversity of time of onset and type of delayed-onset adverse events observed. It seems that invasive facial or oral procedures in the vicinity of filler depots can provoke such complications. We propose a strategy for treating these complications and advise great caution when using permanent filling agents.

Therapeutic hotline: An alternative adjuvant treatment after ear keloid excision using a custom-made methyl methacrylate stent.

The efficacy of most pressure devices developed for treatment of ear keloids is limited by the insufficient control of the applied pressure, sometimes causing pain and repeated bleeding with a subsequently increased risk of infections and cosmetic problems. The present study aims to describe the efficacy of the custom-made methyl methacrylate stent in patients that were surgically treated for ear keloids and afterward underwent pressure therapy. The recurrence rate of the ear keloids was evaluated after at least 12 months. Adjuvant treatment with the methyl methacrylate stent resulted in an 83% success rate in our experience with 23 patients that completed the intended therapeutic duration of 18 months. No cases of severe complications were seen during or after the treatment. Furthermore, all the items of the Patient and Observer Scar Assessment Scale resulted in a statistically significant improvement of the scar (p < 0.05). Postoperative pressure therapy with the custom-made methyl methacrylate stent seems efficacious, safe, and is usable for keloids of both the helix and the earlobe.

Perioperative antibiotics in the setting of microvascular free tissue transfer: current practices.

Microvascular free tissue transfer is a ubiquitous and routine method of restoring anatomic defects. There is a paucity of data regarding the role of perioperative antibiotics in free tissue transfer. We designed a survey to explore usage patterns among microvascular surgeons and thereby define a standard of care. A 24-question survey regarding the perioperative antibiotic use in microvascular head and neck, breast, and lower extremity reconstruction was sent to all those members of the American Society for Reconstructive Microsurgery who had registered e-mail addresses ( N = 450). Ninety-nine members responded. A first-generation cephalosporin is the most frequent choice of perioperative antibiotics across most categories: 93.5% for breast, 59.2% for head and neck, 91.1% for nontraumatic lower extremity, and 84.9% for traumatic noninfected lower extremity reconstruction. In penicillin-allergic patients, clindamycin is the most common choice. For traumatic lower extremity reconstruction in the presence of soft tissue infection or osteomyelitis, culture and sensitivity results determine the selection of perioperative antibiotics in 74%. A first-generation cephalosporin is the standard of care for perioperative antibiotic use in microvascular breast, head and neck, nontraumatic lower extremity, and traumatic noninfected lower extremity reconstruction. No consensus exists regarding the appropriate duration of coverage. These data may serve as a guide until a large controlled prospective trial is performed and a standard of care is established.

A rapidly resorbable hemostatic biomaterial based on dihydroxyacetone.

We have developed a rapid acting, rapidly resorbable, non-toxic, topical hemostatic agent comprised of a PEGylated, polymerized sequence of dihydroxyacetone (MPEG-pDHA) that is highly effective in vivo. Twenty-eight Sprague-Dawley rats underwent left lateral hepatectomy. To the cut edge of the liver, rats received MPEG-pDHA (50 mg), normal saline (0.5 mL), or Instat (50 mg), a commercially available hemostatic compound. Bleeding time and total blood loss were quantified. Coagulation studies and scanning electron microscopy were performed on phlebotomized blood combined with MPEG-pDHA. Rats treated with MPEG-pDHA had significantly decreased bleeding time (97 s) and total blood loss (1.35 g) compared to normal saline (464 s and 3.83 g, p < 0.05 for each), and a significantly shorter bleeding time compared to Instat (165 s, p < 0.05). Histology confirmed that all MPEG-pDHA was metabolized within 3 weeks. The addition of MPEG-pDHA to whole blood did not significantly affect prothrombin time (12.0 s vs. 13.2 s, p = 0.130), partial thromboplastin time (27.0 s vs. 21.8 s, p = 0.118), or thrombin clotting time. MPEG-pDHA is an effective and rapidly resorbable hemostatic agent that may find broad hemostatic application in a wide range of surgical procedures.