Hermansky-Pudlak syndrome: Report of two patients with updated genetic classification and management recommendations.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder caused by mutations in one of nine genes involved in the packaging and formation of specialized lysosomes, including melanosomes and platelet-dense granules. The cardinal features are pigmentary dilution, bleeding diathesis, and accumulation of ceroid-like material in reticuloendothelial cells. Pulmonary fibrosis induced by tissue damage is seen in the most severe forms, and one subtype is characterized by immunodeficiency. We describe two patients with HPS type 1 and review the updated gene-based classification, clinical features, and recommendations for evaluation and follow-up.

Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets.

BACKGROUND: Identifying differences and similarities between cutaneous lymphocyte antigen (CLA)(+) polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children. OBJECTIVE: We sought to compare activation markers and frequencies of skin-homing (CLA(+)) versus systemic (CLA(-)) "polar" CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects. METHODS: Flow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining TH1/cytotoxic T (TC) 1, TH2/TC2, TH9/TC9, TH17/TC17, and TH22/TC22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children less than 5 years old and 42 adults with well-characterized moderate-to-severe AD, as well as age-matched control subjects (17 children and 25 adults). RESULTS: Selective inducible costimulator activation (P < .001) was seen in children. CLA(+) TH2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA(+) TH1 T-cell numbers were greater in children with AD (17% vs 7.4%, P = .007). Unlike in adults, no imbalances were detected in CLA(-) T cells from pediatric patients with AD nor were there altered frequencies of TH22 T cells within the CLA(+) or CLA(-) compartments. Adults with AD had increased frequencies of IL-22-producing CD4 and CD8 T cells within the skin-homing population, compared with controls (9.5% vs 4.5% and 8.6% vs 2.4%, respectively; P < .001), as well as increased HLA-DR activation (P < .01). CONCLUSIONS: These data suggest that TH2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by TH1 T cells might contribute to excess TH2 activation. TH22 "spreading" of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections.

The effect of single low-dose dexamethasone on blood glucose concentrations in the perioperative period: a randomized, placebo-controlled investigation in gynecologic surgical patients.

BACKGROUND: The effect of single low-dose dexamethasone therapy on perioperative blood glucose concentrations has not been well characterized. In this investigation, we examined the effect of 2 commonly used doses of dexamethasone (4 and 8 mg at induction of anesthesia) on blood glucose concentrations during the first 24 hours after administration. METHODS: Two hundred women patients were randomized to 1 of 6 groups: Early-control (saline); Early-4 mg (4 mg dexamethasone); Early-8 mg (8 mg dexamethasone); Late-control (saline); Late-4 mg (4 mg dexamethasone); and Late-8 mg (8 mg dexamethasone). Blood glucose concentrations were measured at baseline and 1, 2, 3, and 4 hours after administration in the early groups and at baseline and 8 and 24 hours after administration in the late groups. The incidence of hyperglycemic events (the number of patients with at least 1 blood glucose concentration >180 mg/dL) was determined. RESULTS: Blood glucose concentrations increased significantly over time in all control and dexamethasone groups (from median baselines of 94 to 102 mg/dL to maximum medians ranging from 141 to 161.5 mg/dL, all P < 0.001). Blood glucose concentrations did not differ significantly between the groups receiving dexamethasone (either 4 or 8 mg) and those receiving saline at any measurement time. The incidence of hyperglycemic events did not differ in any of the early (21%-28%, P = 0.807) or late (13%-24%, P = 0.552) groups. CONCLUSIONS: Because blood glucose concentrations during the first 24 hours after administration of single low-dose dexamethasone did not differ from those observed after saline administrations, these results suggest clinicians need not avoid using dexamethasone for nausea and vomiting prophylaxis out of concerns related to hyperglycemia.

Postoperative residual neuromuscular blockade is associated with impaired clinical recovery.

BACKGROUND: In this investigation, we sought to determine the association between objective evidence of residual neuromuscular blockade (train-of-four [TOF] ratio <0.9) and the type, incidence, and severity of subjective symptoms of muscle weakness in the postanesthesia care unit (PACU). METHODS: TOF ratios of 149 patients were quantified with acceleromyography on arrival to the PACU. Patients were stratified into 2 cohorts: a TOF <0.9 group (n = 48) or a TOF ≥0.9 (control) group (n = 101). A standardized examination determined the presence or absence of 16 symptoms and 11 signs of muscle weakness on arrival to the PACU and 20, 40, and 60 minutes after admission. RESULTS: The incidence of symptoms of muscle weakness was significantly higher in the TOF <0.9 group at all times (P < 0.001), as was the median (range) number of symptoms from PACU arrival (7 [3-6] TOF <0.9 group vs 2 [0-11] control group; difference 5, 99% confidence interval of the difference 4-6) until 60 minutes after admission (2 [0-12] TOF <0.9 group vs 0 [0-11] control group; difference 2, 99% confidence interval of the difference 1-2) (all P < 0.0001). CONCLUSION: The incidence and severity of symptoms of muscle weakness were increased in the PACU in patients with a TOF <0.9.

Intraoperative acceleromyography monitoring reduces symptoms of muscle weakness and improves quality of recovery in the early postoperative period.

BACKGROUND: The subjective experience of residual neuromuscular blockade after emergence from anesthesia has not been examined systematically during postanesthesia care unit (PACU) stays. The authors hypothesized that acceleromyography monitoring would diminish unpleasant symptoms of residual paresis during recovery from anesthesia by reducing the percentage of patients with train-of-four ratios less than 0.9. METHODS: One hundred fifty-five patients were randomized to receive intraoperative acceleromyography monitoring (acceleromyography group) or conventional qualitative train-of-four monitoring (control group). Neuromuscular management was standardized, and extubation was performed when defined criteria were achieved. Immediately upon a patient's arrival to the PACU, the patient's train-of-four ratios were measured using acceleromyography, and a standardized examination was used to assess 16 symptoms and 11 signs of residual paresis. This examination was repeated 20, 40, and 60 min after PACU admission. RESULTS: The incidence of residual blockade (train-of-four ratios less than 0.9) was reduced in the acceleromyography group (14.5% vs. 50.0% control group, with the 99% confidence interval for this 35.5% difference being 16.4-52.6%, P < 0.0001). Generalized linear models revealed the acceleromyography group had less overall weakness (graded on a 0-10 scale) and fewer symptoms of muscle weakness across all time points (P < 0.0001 for both analyses), but the number of signs of muscle weakness was small from the time of arrival in the PACU and did not differ between the groups at any time. CONCLUSION: Acceleromyography monitoring reduces the incidence of residual blockade and associated unpleasant symptoms of muscle weakness in the PACU and improves the overall quality of recovery.

Small-dose dexamethasone improves quality of recovery scores after elective cardiac surgery: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: The use of steroid therapy in cardiac surgical patients remains controversial. The aim of this clinical investigation was to determine the effect of small-dose dexamethasone therapy on patient-perceived quality of recovery (QoR) scores in elective cardiac surgical patients. In addition, the authors assessed the impact of dexamethasone on the incidence of common adverse events after cardiopulmonary bypass (CPB). DESIGN: A prospective, randomized study. SETTING: University hospitals. PARTICIPANTS: One hundred seventeen patients undergoing cardiac surgery with CPB and anticipated early tracheal extubation. INTERVENTIONS: Subjects were randomized to receive either dexamethasone (dexamethasone group, 8 mg at the induction of anesthesia and at the initiation of CPB) or placebo (control group, saline). MEASUREMENTS AND MAIN RESULTS: The QoR was assessed using the QoR-40 scoring system preoperatively and on postoperative days (PODs) 1 and 2. Secondary outcome measures assessed in the postoperative period included nausea, vomiting, fatigue, febrile responses, shivering, pulmonary gas exchange, and analgesic requirements. Global QoR-40 scores (median [range]) were higher in the dexamethasone group compared with the control group on POD 1 (167 [133-192] v 157 [108-195]; p < 0.0001) and POD 2 (173 [140-196] v 166 [122-196]; p = 0.001). In the dexamethasone group, improved QoR was observed in the QoR-40 dimensions of emotional state (p = 0.002), physical comfort (p = 0.0001-0.006), and pain (p < 0.0001). The incidences or severity of postoperative fatigue (p < 0.0001), febrile responses (p < 0.0001), and shivering (p = 0.001) were reduced in the dexamethasone group. CONCLUSIONS: Patient-perceived postoperative QoR in cardiac surgical patients is enhanced significantly by small-dose dexamethasone treatment.

A multimodal approach to the treatment of extensive burn scars: a modified subcision technique for intralesional delivery of corticosteroid and 5-fluorouracil in combination with several procedural laser therapies; a case report.

INTRODUCTION: Hypertrophic scars and keloids are challenging to manage due to recurrence and often sub-optimal response to treatment. There is a lack of both definitive treatment standards and randomised controlled trials comparing therapeutic options. While a wide array of procedures has been utilised to improve traumatic burn scars, such interventions have been used with varying degrees of success. Some reported methods include intralesional injections of anti-inflammatory and anti-mitotic medications, laser-based therapy, topical therapies, cryotherapy, silicone gel sheeting, pressure therapy, radiotherapy and reconstructive surgery. CASE: We report a case of extensive traumatic burn scarring on the head and neck successfully treated with a multimodal approach comprised of an infrequently used modified subcision technique to deliver alternating intralesional injections of anti-inflammatory (high-dose steroid) and anti-metabolite (5-flurouracil) concurrently with a series of laser (epilatory, vascular and fractional) treatments. METHODS: Our treatment modality utilised a subcisional technique to deliver intralesional steroid and anti-metabolite medications directly into scar tissue to downregulate inflammation and inhibit collagen synthesis. Alexandrite, fractional and pulsed dye laser therapy was employed to improve skin texture, reduce dyschromia and reduce tissue burden of hypertrophic scar and keloid tissue, resulting in improved mobility and skin elasticity. CONCLUSION: Our case supports a combined medical and procedural, subcisional, approach to successfully treat a patient with extensive hypertrophic scarring and keloid formation with associated hair entrapment after a head and neck burn.

Perianal extramammary Paget disease treated with topical imiquimod and oral cimetidine.

Extramammary Paget disease (EMPD) is a rare intraepithelial adenocarcinoma. The current mainstay of treatment is wide local excision. We present the case of a 56-year-old woman with perianal EMPD that recurred 4 years after initial treatment with wide local excision with Mohs micrographic surgery tissue processing of marginal tissue. Upon recurrence with anal canal involvement, the patient was treated with a 16-week combination course of topical imiquimod and oral cimetidine. There is growing evidence to support both the use of topical imiquimod for the treatment of EMPD as well as the antioncogenic effects of oral cimetidine. We present this case of primary perianal EMPD to highlight an alternative treatment regimen for poor surgical candidates.

A 20-day-old boy with a blue skin lesion. Noninvoluting congenital hemangioma.

A 20-day-old boy presented for evaluation of a blue nodule on the right shoulder that had been present since birth. The mother noted no changes in the size of the lesion since birth, and no bleeding or ulceration was noted. The patient's past medical history was unremarkable. He was a full-term baby born at 39 weeks gestation via a normal, spontaneous vaginal delivery. The pregnancy was uncomplicated. The mother had no history of maternal hypertension and had no history of chorionic villus sampling or amniocentesis. The patient was not taking any medications and had no known allergies. Physical exam revealed a well-developed, well-nourished male in no apparent distress. A full skin exam revealed a 1.8 cm × 2 cm discrete, blue-purple vascular nodule with coarse surface telangiectasias and a surrounding rim of pallor on the right shoulder. There was no bleeding or breakdown noted. There was no lymphadenopathy present.