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Face vascularized composite allografts (FVCAs) have helped patients with severe facial disfigurement, with acute rejection now largely controlled through iatrogenic immunosuppression. However, little is known regarding the incidence and mechanism(s) of more long-term pathologic alterations in FVCAs that may affect function and graft durability. Protocol surveillance biopsy specimens for up to an 8-year interval in 7 patients who received FVCAs at our institution revealed histopathologic evidence of chronic rejection. Clinical manifestations included features of premature aging, mottled leukoderma accentuating suture lines, telangiectasia, and dryness of nasal mucosa. Pathologic changes consisted of epidermal thinning accompanied by discrete foci of lymphocyte-mediated cytotoxicity, hyperkeratosis, follicular plugging, vascular ectasia, and sclerosis beneath the epidermal layer associated with collagen type I deposition. Genomic interrogation and immunohistochemistry of sclerotic zones revealed upregulation of the AP-1 pathway components, JunB and c-Fos, previously implicated in overproduction of type I dermal collagen in the setting of systemic sclerosis. We conclude that some patients develop chronic rejection in FVCAs with striking similarities to alterations seen in certain autoimmune cutaneous disorders (lupus erythematosus and scleroderma/chronic sclerodermoid graft-versus-host disease). Identification of relevant pathways and genes, such as JunB and c-Fos, may provide new targets for preventative therapies for chronic immune-mediated changes in vascularized composite allografts.

Background Major complications after spine metastasis surgery are prioritized in the literature with little consideration of the more frequent minor events such as pneumonia or urinary tract infection. We analyzed incidence and risk factors of postsurgical complications in patients with spinal metastasis extracted from the National Surgical Quality Improvement Program (NSQIP). We also developed a useful predictive model to estimate the probability of occurrence of complications. Methods A total of 1176 patients diagnosed with spinal metastasis were extracted from NSQIP. Variables screened included age, sex, tumor location, patient’s functional status, comorbidities, laboratory values, and case urgency. Two multivariate logistic regression models were designed to evaluate risk factors and likelihood of event occurrence. Results Minor events occurred twice as frequently compared with major complications (36% vs. 18% of patients). The most common major event was death (10%); the most frequent minor event was need for postoperative transfusion (29.4%). In the multivariate analysis, elderly age, emergency case, preoperative leukocytosis, and smoking status retained significance for major complications; American Society of Anesthesiologists classes 4–5, low hematocrit levels, and intradural extramedullary location of the tumor retained significance for minor complications. The predictive models designed explained 72% of the variability in major complications occurrence and 67% for minor events. Conclusions Smoking status and emergent surgery were found to be the strongest independent predictors of major complications, whereas higher American Society of Anesthesiologists class showed a greater association with minor events. The predictive models produced can be a useful aid for surgeons to identify those patients who are at greater risk of developing postoperative adverse events.

Depression is a common disorder that may go untreated or receive suboptimal care in primary care settings. Computer-assisted cognitive behavior therapy (CCBT) has been proposed as a method for improving access to effective psychotherapy, reducing cost, and increasing the convenience and efficiency of treatment for depression.To evaluate whether clinician-supported CCBT is more effective than treatment as usual (TAU) in primary care patients with depression and to examine the feasibility and implementation of CCBT in a primary care population with substantial numbers of patients with low income, limited internet access, and low levels of educational attainment.This randomized clinical trial included adult primary care patients from clinical practices at the University of Louisville who scored 10 or greater on the Patient Health Questionnaire-9 (PHQ-9) and were randomly assigned to CCBT or TAU for 12 weeks of active treatment. Follow-up assessments were conducted 3 and 6 months after treatment completion. Enrollment occurred from June 24, 2016, to May 13, 2019. The last follow-up assessment was conducted on January 30, 2020.CCBT included use of the 9-lesson computer program Good Days Ahead, along with as many as 12 weekly telephonic support sessions of approximately 20 minutes with a master's level therapist, in addition to TAU, which consisted of the standard clinical management procedures at the primary care sites. TAU was uncontrolled, but use of antidepressants and psychotherapy other than CCBT was recorded.The primary outcome measure (PHQ-9) and secondary outcome measures (Automatic Thoughts Questionnaire for negative cognitions, Generalized Anxiety Disorder-7, and the Satisfaction with Life Scale for quality of life) were administered at baseline, 12 weeks, and 3 and 6 months after treatment completion. Satisfaction with treatment was assessed with the Client Satisfaction Questionnaire-8.The sample of 175 patients was predominately female (147 of 174 [84.5%]) and had a high proportion of individuals who identified as racial and ethnic minority groups (African American, 44 of 162 patients who reported [27.2%]; American Indian or Alaska Native, 2 [1.2%]; Hispanic, 4 [2.5%]; multiracial, 14 [8.6%]). An annual income of less than $30 000 was reported by 88 of 143 patients (61.5%). Overall, 95 patients (54.3%) were randomly assigned to CCBT and 80 (45.7%) to TAU. Dropout rates were 22.1% for CCBT (21 patients) and 30.0% for TAU (24 patients). An intent-to-treat analysis found that CCBT led to significantly greater improvement in PHQ-9 scores than TAU at posttreatment (mean difference, -2.5; 95% CI, -4.5 to -0.8; P = .005) and 3 month (mean difference, -2.3; 95% CI, -4.5 to -0.8; P = .006) and 6 month (mean difference, -3.2; 95% CI, -4.5 to -0.8; P = .007) follow-up points. Posttreatment response and remission rates were also significantly higher for CCBT (response, 58.4% [95% CI, 46.4-70.4%]; remission, 27.3% [95% CI, 16.4%-38.2%]) than TAU (response, 33.1% [95% CI, 20.7%-45.5%]; remission, 12.0% [95% CI, 3.3%- 20.7%]).In this randomized clinical trial, CCBT was found to have significantly greater effects on depressive symptoms than TAU in primary care patients with depression. Because the study population included people with lower income and lack of internet access who typically have been underrepresented or not included in earlier investigations of CCBT, results suggest that this form of treatment can be acceptable and useful in diverse primary care settings. Additional studies with larger samples are needed to address implementation procedures that could enhance the effectiveness of CCBT and to examine potential factors associated with treatment outcome.ClinicalTrials.gov Identifier: NCT02700009.

Objectives The goal of this study was to detect and explore the mechanisms of the succinate dehydrogenase (SDH) complex subunit-related gene mutations in cases of multiple paraganglioma (PGL) in the head and neck. Methods In Beijing Tongren Hospital (Capital Medical University, Beijing, People's Republic of China) between January 2013 and February 2017, 23 cases of head and neck multiple PGL were evaluated by genetic sequencing. From these cases, four hereditary families and 10 cases with sporadic occurrences were found. Gene mutations, including SDHD, SDHB, SDHC, SDHAF2, VHL and RET in germ cells and somatic cells, were detected by gene capture and high throughput sequencing. Results In family 1, 12 instances of SDHD gene mutation were detected, eight of which manifested as bilateral carotid body tumor (CBT) with one bilateral malignant CBT. In family 2, three cases of SDHD mutation were found with one case of bilateral CBT and two cases of unilateral CBT. In family 3, two cases of SDHD gene mutation were found, both characterized by vagus PGL and pheochromocytoma. Of the 10 patients with sporadic manifestations, five cases of SDHD gene mutation and one case of RET gene mutation were detected. Two novel gene mutations, c.387_393del7 mutation of SDHD gene and c.3247A>G mutation of RET gene, were also detected. Conclusion In patients with multiple PGL in the head and neck, these are accompanied by a genetic mutation of the germ cell. In this case study, this mutation was most commonly a mutation of the SDHD gene. Level of evidence 4 Laryngoscope, 129:E67-E71, 2019.

BackgroundHuman herpesvirus-6 (HHV-6) is a ubiquitous double-stranded DNA virus that can cause roseola infantum, encephalitis, and seizure disorders. Several studies have shown an association between HHV-6 and cancer but confirmation of an etiologic role is lacking. We reviewed the criteria for viral causation of cancer used by The International Agency for Research on Cancer (IARC) for six oncogenic viruses and applied criteria to published reports of HHV-6 and its association with Hodgkin lymphoma and brain tumors.MethodsOur major criteria for oncogenicity were finding evidence of the virus in every tumor cell and prevention of the tumor by an antiviral vaccine. Our six minor criteria included: 1) suggestive serologic correlation, such as higher virus antibody levels in cases compared to controls; 2) evidence of the virus in some but not all tumor cells, and 3) time space clustering. We focused on Epstein-Barr virus (EBV) as the primary virus for comparison as HHV-6 and EBV are both Herpesviridae, ubiquitous infections, and EBV is well-accepted as a human oncovirus. Particular attention was given to Hodgkin lymphoma (HL) and brain cancer as these malignancies have been the most studied.ResultsNo studies reported HHV-6 satisfying either of the major criteria for oncogenicity. Of the minor criteria used by IARC, serologic studies have been paramount in supporting EBV as an oncogenic agent in all EBV-associated tumors, but not for HHV-6 in HL or brain cancer. Clustering of cases was suggestive for both HL and brain cancer and medical intervention suggested by longer survival in patients treated with antiviral agents was reported for brain cancer.ConclusionThere is insufficient evidence to indicate HHV-6 is an etiologic agent with respect to HL and brain cancers. We suggest that methods demonstrating EBV oncogenicity be applied to HHV-6. It is important that one study has found HHV-6 in all cancer cells in oral cancer in a region with elevated HHV-6 antibodies and therefore HHV-6 can still be considered a possible human oncogenic virus.

Epigenetic regulation has a profound influence on stem cell fate during normal development in maintenance of physiologic tissue homeostasis. Here we report diminished ten-eleven translocation (TET) methylcytosine dioxygenase expression and loss of the DNA hydroxymethylation mark 5-hydroxymethylcytosine (5-hmC) in keratinocyte stem cells and transit amplifying cells in human psoriasis and in imiquimod-induced murine psoriasis. Loss of 5-hmC was associated with dysregulated keratinocyte stem cell kinetics, resulting in accumulation of nestin and FABP5-expressing transit amplifying cells to produce classic psoriatic epidermal architecture. Moreover, 5-hmC loss was accompanied by diminished TET1 and TET2 mRNA expression. Genome-wide mapping of epidermal 5-hmC in murine psoriasis revealed loci-specific loss of 5-hmC in genes regulating stem cell homeostasis, including MBD1, RTN1, STRN4, PRKD2, AKT1, and MAPKAP2, as well as those associated with RAR and Wnt/β-catenin signaling pathways. In vitro restoration of TET expression by ascorbic acid was accomplished in cultured human keratinocyte stem cells to show similar Ca++-induced differentiation, resulting in increased 5-hmC levels and reduced nestin expression. To our knowledge, an epigenetic deficiency in psoriasis with relevance to stem cell dysregulation has not been previously reported. This observation raises the possibility that epigenetic modifiers that impact on the TET–5-hmC pathway may be a relevant approach of heretofore unappreciated therapeutic utility.

Background Hair follicle (HF) cycling is dependent upon activation and differentiation of an epithelial subpopulation of cells with stem-like characteristics. These cells express cytokeratin 15 (CK15) and are sequestered within a specialized niche termed the follicular bulge. The pathways that mediate bulge activation are poorly understood, although growing evidence suggests a role for epigenetic events. Methods Here we investigated murine and human HFs to determine whether a recently described epigenetic hydroxymethylation marker, 5-hmC, known to mediate cell growth and differentiation, may play a role in bulge activation. Results We found the bulge region of murine HFs to show variable 5-hmC distribution within the nuclei of CK15-positive stem cells during early anagen, a pattern that was not associated with resting stem cells of telogen follicles, which did not express 5-hmC. Moreover, during phases of early anagen that were induced in an organ culture model, spatial alterations in bulge stem cell 5-hmC reactivity, as assessed by dual labeling, were noted. Conclusions These preliminary findings suggest that 5-hmC may play a dynamic role in bulge activation during anagen growth, and provide a foundation for further experimental inquiry into epigenomic regulation of HF stem cells.

Computer-assisted cognitive-behavior therapy (CCBT) for depression in primary care will be evaluated in a trial with 240 patients randomly assigned to CCBT or treatment as usual (TAU). The study will disseminate a therapy method found to be effective in psychiatric settings into primary care - a setting in which there have been significant problems in the delivery of adequate, evidence-based treatment for depression. The study will include a high percentage of disadvantaged (low-income) patients - a population that has been largely ignored in previous research in CCBT. There have been no previous studies of CCBT for depression in primary care that have enrolled large numbers of disadvantaged patients. The form of CCBT used in this study is designed to increase access to effective therapy, provide a cost-effective method, and be a sustainable model for wide-spread use in primary care. In order to deliver therapy in a practical manner that can be replicated in other primary care practices, patients with significant symptoms of depression will receive treatment with an empirically supported computer program that builds cognitive-behavior therapy skills. Support for CCBT will be provided by telephone and/or e-mail contact with a care coordinator (CC) instead of face-to-face treatment with a cognitive-behavior therapist. Outcome will be assessed by measuring CCBT completion rate, comprehension of CBT concepts, and satisfaction with treatment, in addition to ratings of depressive symptoms, negative thoughts, and quality of life. The cost-effectiveness analysis and exploration of possible predictors of outcome should help clinicians, health care organizations, and others plan further dissemination of CCBT in primary care.

Objective To examine evidence for the effectiveness of computer-assisted cognitive-behavior therapy (CCBT) for depression in primary care and assess the impact of therapist-supported CCBT versus self-guided CCBT. Methods A search for randomized studies of CCBT compared to control groups for treating depression in primary care settings was conducted using Ovid MEDLINE, PsycINFO, PubMed, and Scopus. We extracted the following information from the studies that met inclusion criteria: mean depression rating scale scores before and after treatment, number of patients, type of control group and CCBT program, therapist support time and method of support, and treatment completion rate. Meta-analyses compared differences between posttreatment mean scores in each condition, as well as mean scores at follow-up. Study quality and possible bias also were assessed. Results Eight studies of CCBT for depression in primary care met inclusion criteria. The overall effect size was g = 0.258, indicating a small but significant advantage for CCBT over control conditions. Therapist support was provided in 4 of the 8 studies. The effect size for therapist-supported CCBT was g = 0.372-a moderate effect. However, the effect size for self-guided CCBT was g = 0.038, indicating little effect. Conclusions Implementation of therapist-supported CCBT in primary care settings could enhance treatment efficiency, reduce cost, and improve access to effective treatment for depression. However, evidence to date suggests that self-guided CCBT offers no benefits over usual primary care.

The authors present a case illustrating the importance of obtaining a biopsy of any facial skin lesions in a patient presenting with an intracranial tumor involving the facial or trigeminal nerve. Conventional malignant melanoma metastasizes to the brain frequently and does not usually pose diagnostic difficulties. Direct intracranial spread of cutaneous melanoma is rare. In our patient, desmoplastic melanoma with perineural spread to the Meckel cave mimicked a malignant peripheral nerve sheath tumor clinically, radiographically, and histologically.

Instructions: In answering each question, refer to the specific directions provided. Because it is often necessary to provide information occurring later in a series that give away answers to earlier questions, please answer the questions in each series in sequence.

Rolipram, an inhibitor of phosphodiesterase 4 (PDE4) proteins that hydrolyze cAMP, increases axonal regeneration following spinal cord injury (SCI). Recent evidence indicates that rolipram also protects against a multitude of apoptotic signals, many of which are implicated in secondary cell death post-SCI. In the present study, we used immunohistochemistry and morphometry to determine potential spinal cord targets of rolipram and to test its protective potential in rats undergoing a cervical spinal cord contusive injury. We found that 3 PDE4 subtypes (PDE4A, B, D) were expressed by spinal cord oligodendrocytes. OX-42 immunopositive microglia only expressed the PDE4B subtype. Oligodendrocyte somata were quantified within the cervical ventrolateral funiculus, a white matter region critical for locomotion, at varying time points after SCI in rats receiving rolipram or vehicle treatments. We show that rolipram significantly attenuated oligodendrocyte death at 24 hours post-SCI continuing through 72 hours, the longest time point examined. These results demonstrate for the first time that spinal cord glial cells express PDE4 subtypes and that the PDE4 inhibitor rolipram protects oligodendrocytes from secondary cell death following a contusive SCI. They also indicate that further investigations into neuroprotection and axonal regeneration with rolipram are warranted for treating SCI.

Varying degrees of neurologic function spontaneously recovers in humans and animals during the days and months after spinal cord injury (SCI). For example, abolished upper limb somatosensory potentials (SSEPS) and cutaneous sensations can recover in persons post-contusive cervical SCI. To maximize recovery and the development/evaluation of repair strategies, a better understanding of the anatomical locations and physiological processes underlying spontaneous recovery after SCI is needed. As an initial step, the present study examined whether recovery of upper limb SSEPs after contusive cervical SCI was due to the integrity of some spared dorsal column primary afferents that terminate within the cuneate nucleus and not one of several alternate routes. C5-C6 contusions were performed on male adult rats. Electrophysiological techniques were used in the same rat to determine forelimb evoked neuronal responses in both cortex (SSEPS) and the cuneate nucleus (terminal extracellular recordings). SSEPs were not evoked 2 days post-SCI but were found at 7 days and beyond, with an observed change in latencies between 7 and 14 days (suggestive of spared axon remyelination). Forelimb evoked activity in the cuneate nucleus at 15 but not 3 days post-injury occurred despite dorsal column damage throughout the cervical injury (as seen histologically). Neuroanatomical tracing (using 1% unconjugated cholera toxin B subunit) confirmed that upper limb primary afferent terminals remained within the cuneate nuclei. Taken together, these results indicate that neural transmission between dorsal column primary afferents and cuneate nuclei neurons is likely involved in the recovery of upper limb SSEPs after contusive cervical SCI.

Instructions: In answering each question, refer to the specific directions provided. Because it is often necessary to provide information occurring later in a series that give away answers to earlier questions, please answer the questions in each series in sequence.

Castori M, Ruggieri S, Giannetti L, Annessi G, Zambruno G. Sch€ opf-Shulz-Passarge syndrome: further delineation of the phenotype and genetic considerations. Acta Derm Venereol 2008;88:607-12. Craigen WJ, Levy ML, Lewis RA. Sch€ opf-Schulz-Passarge syndrome with an unusual pattern of inheritance. Am J Med Genet 1997; 71:186-8. Gira A, Robertson D, Swerlick R. Multiple eyelid cysts with palmoplantar hyperkeratosis. Arch Dermatol 2004;140:231-6. Gordon M, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem 2006; 281:22429-33. Hampton PJ, Angus B, Carmichael AJ. A case of Sch€ opf-SchulzPassarge syndrome. Clin Exp Dermatol 2005;30:528-30. James W, Berger T, Elston D, editors. Andrews’ diseases of the skin: clinical dermatology. 10th ed. New York: Elsevier; 2006. Monk BE, Pieris S, Soni V. Sch€ opf-Schulz-Passarge syndrome. Br J Dermatol 1992;127:33-5. Online Medelian Inheritance in Man. Johns Hopkins University, Baltimore, MD. MIM number: 224750. Available at: http:// www.ncbi.nlm.nih.gov/omim. Accessed August 29, 2011. Sch€ opf E, Schulz H-J, Passarge E. Syndrome of cystic eyelids, palmo-plantar keratosis, hypodontia and hypotrichosis as a possible autosomal recessive trait. Birth Defects 1971;8: 219-21. Starink TM. Eccrine syringofibroadenoma: multiple lesions representing a new cutaneous marker of the Sch€ opf syndrome, and solitary nonhereditary tumors. J Am Acad Dermatol 1997;36: 569-76. Verplanke P, Driessen L, Wynants P, Naeyaert J. The Sch€ opf-Schulz-Passarge syndrome. Dermatology 1998;196: 463-6.

Griffin LJ, Massa MC. Acquired ichthyosis and pityriasis rotunda. Clin Dermatol 1993;11:27-32. Okulicz JF, Schwartz RA. Hereditary and acquired ichthyosis vulgaris. Int J Dermatol 2003;42:95-8. Patel N, Spencer LA, English JC 3rd, Zirwas MJ. Acquired ichthyosis. J Am Acad Dermatol 2006;55:647-56. Schwartz RA, Williams ML. Acquired ichthyosis: a marker for internal disease. Am Fam Physician 1984;29:181-4. Weiss P, O’Rourke ME. Cutaneous paraneoplastic syndromes. Clin J Oncol Nurs 2000;4:257-62.

Lichen planopilaris (LPP) is a primary cicatricial alopecia that rarely presents in a linear distribution. We present a case of linear LPP that was isolated to the frontal scalp with extension down the forehead. It is uncommon to see a linear distribution of LPP anywhere on the body, but it is particularly rare on the scalp. We also discuss the pathophysiology of disorders that present in unusual linear distributions.

IntroductionPeptide bond cleavage can herald the end of a protein’s active life, or its transformation from an inactive precursor to an active enzyme. If the newly activated protein is a proteinase, even a highly specific proteinase, then its activity must be regulated in order that unbridled cleavage and damage to the host organism do not ensue. Such regulation for many of the key serine proteinases of the coagulation, fibrinolytic, complement, and inflammatory pathways is provided by the inhibitory proteins of the serpin family.The serpins are a large family of over 100 proteins (1). Many are plasma proteins such as antithrombin (AT), α1-proteinase inhibitor (α-PI), α1-antichymotrypsin (α-AC), heparin cofactor II (HCII), plasminogen activator inhibitors (PAI) I and II, α2-antiplasmin (α2-AP) and proteinase nexin I (PN-1). While some serpins are readily recognizable as family members, solely by virtue of homology, others have been characterized in detail, particularly those that are suicide inhibitors of their cognate proteinases; enzymes that recognize and attack the reactive centre loop of the inhibitory serpins. The resulting serpin-enzyme complex (SEC) is comprised of the inhibitor, which is irreversibly inactivated by virtue of the cleavage of its reactive centre peptide bond, and the enzyme, which is reversibly inactivated by the formation of an acyl ester linkage between its active site serine and a serpin side chain. Thus, a stable, covalent, and stoichiometric complex resistant to denaturation is formed (2, 3).The reversible nature of the proteinase’s inactivation in the SEC means that while substantial regulation of the proteinase has been achieved, the organism has only prolonged the inevitable by forming the SEC. Because the SEC is only kinetically but not thermodynamically stable, given sufficient time it will break down, releasing cleaved serpin and active enzyme (4, 5). To prevent this, receptor-mediated mechanisms have evolved to effectively remove SECs from the circulation. Since the initial studies of Ohlsson, who investigated the clearance of α-PI-trypsin complexes in the circulation of dogs (6, 7), a large body of evidence has accumulated to indicate that SECs are cleared from the circulation more rapidly than their constituent serpins. This accelerated clearance seals the fate of the serpin-complexed proteinases, and prevents their release from SECs by sequestering the SECs inside cells, where they are catabolized. In this article, we review the available data with respect to the mechanisms involved in SEC removal from the circulation. Specifically, we address those proteins or molecules that have been reported to act as cellular receptors for SEC removal, and propose a model for SEC removal which includes several of the available candidate receptors. Where possible, we have focussed on the thrombin-antithrombin (TAT) complex, both because of our laboratory’s longstanding interest in antithrombin, and because of thrombin’s key role in haemostasis and thrombosis (8).

Background. The “unsuture” technique originally reported with the use of fast-absorbing gut for the placement of full-thickness skin grafts has provided years of successful full-thickness graft placement without the need for suture removal. Objective. The objective was to explore another option for successful graft placement and survival using irradiated polyglactin 910 (Vicryl Rapide, Ethicon Inc, Somerville, NJ, USA), with its longer tensile strength of 7 to 10 days. Methods. Irradiated polyglactin 910 was used to suture the edges and place basting sutures in full-thickness skin grafts. Results. In our experience, we have found that the use of irradiated polyglactin 910 for the placement of full-thickness skin grafts provides an alternative to the “unsuture” technique with fast-absorbing gut. It provides excellent graft survival, easy workability, low inflammation, and good long-term cosmesis, without the need for suture removal. Conclusion. Irradiated polyglactin 910 provides another option for the placement of full-thickness skin grafts without the need for suture removal. AMY R. BRACKEEN, MD, MICHAEL J. WELLS, MD, AND JEFF M. FREED, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.

The prevalence of antithrombin (AT) deficiency in the general population has been variously estimated to be between 0.05 and 5 per 1,000 in the population; 2,491 blood donors were screened in an attempt to clarify this issue using plasma samples taken from the blood donor units. From this initial population, 122 individuals were identified as having plasma AT levels lower than 2 standard deviations below the normal mean. Twenty-two samples had evidence that thrombin had been generated during blood collection and the remaining cohort of 100 blood donors were asked to return but only 59 complied. The data obtained from these 59 were compared with that from 51 age- and sex-matched control blood donors. Both groups of subjects were assessed for previous evidence, or family history, of thrombotic events, as well as exposure to risk factors associated with the development of deep vein thrombosis (DVT). All had venous blood samples taken from which the supernatant plasma was immediately removed and quick frozen for later assaying. Only 6 of the 59 subjects with initial low AT levels had repeat AT-Xa levels below 0.80 units/ml (normal range 0.94 +/- 0.14). Upon repeating the AT-Xa determinations on new samples from these six individuals, only three were found again to be low. One was found to have a type 3 AT deficiency (an Arg47Cys substitution). The other two with a low AT level had mean functional AT-Xa levels of 0.61 and 0.71 units/ml, respectively, with correspondingly low AT:Ag levels consistent with a type 1 AT deficiency. Two of these three subjects has been in high risk situations without evidence of having developed DVT and none had evidence of venous reflux on Doppler venography. In addition, none had personal or family histories of previous thrombotic events. These present data indicate that the prevalence of AT deficiency in our blood donor population is 2 per 1,000 (95% confidence intervals: 0.7-6/1,000).

SummaryObjectives: To determine whether functional antithrombin III (AT-III) levels measured by a factor Xa inhibition (AT-III-Xa) assay identifies AT-III deficient individuals more reliably than functional AT-III levels measured by a thrombin inhibition (AT-III-IIa) assay.Study design: Cross-sectional study.Patient population: Sixty-seven members of a large family with type 2 AT-III deficiency.Intervention: DNA analysis was used as the reference diagnostic standard for AT-III status and subjects were classified as AT-III deficient or non deficient according to these results. Functional AT-III levels were measured in all subjects using: 1) a chromogenic substrate for thrombin and added human thrombin (AT-III-IIa), and 2) a chromogenic substrate for factor Xa and added bovine factor Xa (AT-III-Xa). Functional heparin cofactor II (HC-II) levels were measured using a commercially available kit. The proportions of 125I-α-thrombin complexed to AT-III and HC-II were measured by polyacrylamide gel electrophoresis and autoradiography.Results: Thirty-one (46%) individuals were classified as AT-III deficient and 36 (54%) as AT-III non deficient. AT-III-Xa assay measured a significantly lower mean AT-III value and a narrower range for individuals classified as AT-III deficient than the AT-III-IIa assay. Using the AT-III-IIa assay, six subjects had borderline AT-III levels compared to none with the AT-III-Xa assay. Thrombin inhibition by HC-II likely accounts for the AT-III-IIa assay giving higher values than the AT-III-Xa assay since 1) there was a significant correlation between the difference in AT-III-IIa and AT-III-Xa levels and HC-II levels, 2) the mean level of HC-II was significantly higher for individuals who had a positive difference between AT-III-IIa and AT-III-Xa levels compared to those who had a negative difference and 3) there was a significant correlation between the difference in AT-III-IIa and AT-III-Xa levels and the percentage of 125I-α-thrombin complexed to HC-II.Conclusion: The AT-III-Xa assay is a better discriminant between AT-III deficient and AT-III non deficient individuals than the AT-III-IIa assay.

Mohs micrographic surgery (MMS) has been shown to reduce recurrence rates when used to excise many different mucocutaneous neoplasms, especially of the head and neck. The low recurrence rates are due to careful microscopic evaluation of the horizontal and vertical surgical margins. This article discusses the utility and limitations of MMS in controlling neoplasia of the male genitalia. Specific penoscrotal neoplasias discussed in this article include invasive and in situ squamous cell carcinoma, basal cell carcinoma, extramammary Paget disease, and granular cell tumor.

Efaluzimab has recently been described as a treatment for alopecia areata. Conflicting reports and studies have spurred discussion as to whether efaluzimab is an effective treatment of alopecia areata. Proposed mechanisms for this immune-modifying agent have suggested that efficacy is derived from efaluzimab's effects on T cells. However, a recent molecular study found no alteration in T cell action around hair follicles at six months of treatment and thus the study concluded that efaluzimab was not an effective treatment. This article describes a nine-year-old male with recalcitrant alopecia totalis for seven years who had been nonresponsive to therapeutic intervention. He was started on efaluzimab for severe atopic dermatitis and began to re-grow scalp hair at one year of treatment. This discussion suggests that longer treatment durations may be needed for treatment effects to be seen in some patients.

At the conclusion of this learning activity, physician participants should be able to assess their own diagnostic and patient management skills and use the results of this exercise to help determine personal learning needs that can be addressed through subsequent CME involvement. Instructions for claiming CME credit appear in the front advertising section. See last page of Contents for page number. Instructions: In answering each question, refer to the specific directions provided. Because it is often necessary to provide information occurring later in a series that gives away answers to earlier questions, please answer the questions in each series in sequence.

The prolonged presence of superficial mucosal sutures or perineal sutures may cause irritation or discomfort and increase the risk of bacterial infections. Although absorbable sutures are commonly used in mucosal areas, many sutures have a prolonged half-life and might still require removal when used superficially. We highlight the use of irradiated polyglactin 910 (IRPG) for closure of mucosal defects and areas where short-term wound support is required. We used IRPG in 50 patients for closure of defects on the lips, oral mucosa, and penis. In all cases, IRPG sutures provided appropriate tensile strength with minimal inflammation, suppuration, or irritation. IRPG resulted in low inflammatory response, rapid degeneration, soft feel, and easy workabil-ity, making it an ideal suture option for closure of mucosal defects and areas where short-term wound support is desired.

Generalized urticaria is an adverse and serious side effect of diphencyprone. We report a case in order to advise of the possibility of associated type I hypersensitivity reaction (urticaria), which could progress to a more severe or life-threatening adverse reaction.

Exogenous copper is a well-known cause of blue-green dyspigmentation of the hair, nails, and skin. We report the case of a patient with a blue-green discoloration of multiple seborrheic keratoses on his chest and back after swimming in a pool for rehabilitation of a back injury. Metallic analysis using atomic absorption spectrometry was performed on water samples from both the swimming pool and the hot tub the patient was using. Our dermatology clinic tap water was used as a control. Results of this analysis revealed an elevated level of copper in the swimming pool (2.750 ppm) and normal levels in the hot tub (0.502 ppm) and the control sample (0.891 ppm). The copper level in the swimming pool was more than double the recommended maximum set forth by the US Environmental Protection Agency. After the patient discontinued water exercises in the swimming pool, the green discoloration of the seborrheic keratoses disappeared rapidly. We believe this case represents the first report in the literature of the discoloration of epidermal growths secondary to exogenous heavy metal exposure.

Background. Mohs surgery often uses the creation of a “beveled edge” of 45 degrees during the staged excision of skin cancers. Reconstruction of these defects frequently requires the use of full-thickness skin grafts. Because most wounds are best repaired with 90-degree edges, the beveled incision technique often used in Mohs micrographic surgery creates a wound that may need to be modified prior to reconstruction. Objective. We present a method of harvesting the graft with a similar 45-degree angle beveled incision. Methods. After marking, preparing, locally anesthetizing, and draping the donor site, the graft is harvested using a 45-degree angled incision. Any remaining fat is trimmed away from the base of the graft. The graft is then placed directly on the surgical defect without any “freshening” of the wound edges and is sutured into place. Results. The graft takes well on the surgically created defect, leaving a cosmetically acceptable result. Conclusion. We have found that harvesting the graft with a beveled incision of 45 degrees, similar to taking Mohs stages, hastens the repair process. This obviates the need to remove normal tissue to create a 90-degree angle and allows for better approximation of the dermal surface area of the graft to the base of the defect.

We report 2 patients with documented chronic hepatitis C infection and epidermolysis bullosa acquisita (EBA). Both patients clinically represent classic EBA, exhibiting skin fragility and blistering occurring both spontaneously and secondary to trauma, which heal with milia and scar formation. EBA often is a disease of altered immune status and debility. Further work is necessary to show whether hepatitis C plays a causative role in EBA in these 2 patients and in general.