Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019.

OBJECTIVES: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. RESULTS: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). CONCLUSIONS: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.

Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients.

BACKGROUND: Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. METHODS: We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. RESULTS: Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). CONCLUSIONS: The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period.

Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant-Associated Infection Surveillance Network (TRANSNET).

BACKGROUND: Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. METHODS: Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. RESULTS: A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. CONCLUSIONS: This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.

Evidence-based medicine: facial skin malignancy.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Identify common precancerous and malignant cutaneous growths of the head and neck. 2. Recommend surgical treatment, including margins, based on consensus guidelines. 3. Counsel patients as to available evidence for expected recurrence, follow-up, and morbidity. SUMMARY: Skin lesion excision is the most common procedure performed by plastic surgeons. Because of the cumulative risk factors of sun and carcinogen exposure, the head and neck are the most frequently affected regions of the body. Timely diagnosis and treatment are critical for preventing continued spread and metastasis, and it is incumbent on the treating physician to make the appropriate recommendations for surgical margin and the possibility of adjuvant therapy to prevent recurrence and optimize long-term survival. As clinical guidelines are developed from ongoing outcome studies, new generations of treatment recommendations are continuously in development. Therefore, a systematic review of the most relevant guidelines and clinically rigorous studies was performed with a summarization of treatment recommendations for the following: actinic keratosis, Bowen disease (squamous cell in situ), basal cell carcinoma, squamous cell carcinoma, malignant melanoma, and Merkel cell carcinoma of the head and neck.

Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy.

BACKGROUND: The Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Study 403) demonstrated that zoster vaccine was efficacious through 4 years after vaccination. The Short-Term Persistence Substudy (STPS) was initiated after the SPS to further assess the persistence of vaccine efficacy. METHODS: The STPS re-enrolled 7320 vaccine and 6950 placebo recipients from the 38 546-subject SPS population. Methods of surveillance, case determination, and follow-up were analogous to those in the SPS. Vaccine efficacy for herpes zoster (HZ) burden of illness, incidence of postherpetic neuralgia (PHN), and incidence of HZ were assessed for the STPS population, for the combined SPS and STPS populations, and for each year through year 7 after vaccination. RESULTS: In the STPS as compared to the SPS, vaccine efficacy for HZ burden of illness decreased from 61.1% to 50.1%, vaccine efficacy for the incidence of PHN decreased from 66.5% to 60.1%, and vaccine efficacy for the incidence of HZ decreased from 51.3% to 39.6%, although the differences were not statistically significant. Analysis of vaccine efficacy in each year after vaccination for all 3 outcomes showed a decrease in vaccine efficacy after year 1, with a further decline thereafter. Vaccine efficacy was statistically significant for the incidence of HZ and the HZ burden of illness through year 5. CONCLUSIONS: Vaccine efficacy for each study outcome was lower in the STPS than in the SPS. There is evidence of the persistence of vaccine efficacy through year 5 after vaccination but, vaccine efficacy is uncertain beyond that point.

False-positive Aspergillus galactomannan assay in solid organ transplant recipients with histoplasmosis.

Post-transplantation histoplasmosis may be acquired via inhalation, may result from endogenous reactivation, or may be derived from the allograft. The Histoplasma and Aspergillus enzyme-linked immunoassays are increasingly being relied upon for rapid diagnosis of fungal infections, especially in immunocompromised patients. We describe 4 cases of solid organ transplant recipients who had histoplasmosis and a falsely positive Aspergillus galactomannan (GM) obtained from the serum or bronchoalveolar lavage (BAL) fluid. We also report our experience, testing for Histoplasma antigen (Ag) in specimens positive for Aspergillus GM. From January 2007 through December 2010, of 2432 unique patients who had positive Aspergillus GM tests, 514 (21%) were tested for Histoplasma Ag, and 27 were found to be positive. Most specimens that tested positive for both Aspergillus and Histoplasma were obtained by BAL. False-positive tests for Aspergillus GM can occur in immunosuppressed patients who have histoplasmosis, and may obscure the correct diagnosis.

Cutaneous sarcoidosis and malignancy: An association between sarcoidosis with skin manifestations and systemic neoplasia.

BACKGROUND: Whereas the association between multisystem and pulmonary sarcoidosis and malignancy has been documented, a relationship between cutaneous sarcoidosis and neoplasia has not yet been reported. Because cutaneous manifestations are seen in 20-25 percent of cases of sarcoidosis, this association deserves further investigation. METHODS: We reviewed the relevant literature, in addition to our case series, for a total of 110 cases of cutaneous and non-cutaneous sarcoidosis associated with malignancy with the aim of analyzing possible associations between cutaneous sarcoidosis and malignancy and to enhance the dermatologist's understanding of their critical role in the management of this disease. A search for consecutive cases, which were encountered during the past 20 years, identified 10 cases of confirmed cutaneous sarcoidosis. A review of the relevant literature was also conducted to identify cases of malignancy associated with cutaneous and non-cutaneous sarcoidosis. RESULTS: Cutaneous localization of sarcoidosis was identified in 58 of 100 patients with sarcoidosis and cancer found in the literature (58%) and in 4 of 10 patients in our series (40%). In our series, all cases manifested solid tumors, including breast (n=4 tumors), prostate cancer, colon cancer, kidney cancer, and squamous cell carcinoma of the skin (n=1 of each type). Among the 6 patients in our series with cancers and non-cutaneous sarcoidosis, the types of neoplasias encountered were renal cancer (n=1), mycosis fungoides (n=1), diffuse large B-cell lymphoma (n=1), colon cancer (n=1), and ADK of parotid (n=2). Neoplasias developed after an average of 7.14 years in the literature cases and eight years in our series, following the diagnosis of sarcoidosis. Among the 100 cases of cutaneous (n=58) and non-cutaneous (n=42) sarcoidosis associates with malignancy, which were extracted from the literature, hematologic malignancies accounted for 73 percent of cases and sarcoidosis preceded the detection of neoplasia in a majority (76%) of cases. Among 110 total cases analyzed in this paper, cutaneous sarcoidosis was confirmed in 56.4 percent of overall cases, a figure exceeding expected rates of cutaneous involvement (20-25%) in the general sarcoidosis population. CONCLUSIONS: Sarcoidosis with cutaneous manifestations appears to be associated with malignancy, possibly at a higher rate than other systemic forms of sarcoidosis. The predominant occurrence of sarcoidosis before the development of neoplasia may indicate that an immune dysregulation, such as impairment of cellular immunity mediated by sarcoidosis or the effects of treatment may contribute to an increased risk of malignancy in predisposed individuals. Physician recognition of this link between sarcoidosis and malignancy is critical. Dermatologists, in particular, play an important role, given that many of these associated cases manifest initially, or even solely, with cutaneous findings.

On the missing link between inflammation and cancer.

A various array of cutaneous granulomatous disorders have been found to be associated with internal malignancy. Among them, sarcoidosis, granuloma anulare (GA), psoriasis, pyoderma gangrenosum (PG), or other neutrophilic dermatoses such as the Sweet syndrome and subcorneal pustular dermatosis may precede the development of a neoplastic process by months or years. Pathogenic links of inflammation with cancer are discussed, including inflammation, intrinsic immune dysfunction, cytokines and interleukins, angiogenetic factors, and epigenetic changes.

Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.

[The role of lung volume measurements by plethysmography in the follow-up of asthma in children]. / Intérêt de la mesure des volumes pulmonaires par pléthysmographie corporelle dans le suivi de l'asthme de l'enfant.

In asthmatic children, control of the disease is perfect when no symptoms occur and lung function is normal. The aim of this study is to analyse the role of plethysmography in the follow-up of asthmatic children. We present the results of a retrospective study of lung function (plethysmography and forced expiratory flow) in about 100 asthmatic children aged five to 16years. FEV1/FVC less than 80% predicted was considered as pathological (airflow obstruction). The ratio RV/TLC was considered pathological if greater than 30% and RV was considered pathological if greater than 120% (lung hyperinflation). Bronchodilator reversibility was performed in all patients. All patients were studied in a stable condition. None had developed any asthmatic exacerbations during the past month. We found a significant correlation between the residual volume/total lung capacity (RV/TLC) ratio and, on one hand: FEV1 (p<0.0001, R=-0.374), and on the other hand FEV1/FVC (p=0.07, R=-0.182) or forced expiratory flow 25-75 (p=0.03, R=-0.216). When comparing children with (n=40) and without (n=60) lung hyperinflation, we noticed more diurnal symptoms (30/40 vs 10/60, p=0.05), lower weight (33.9kg vs 41.8kg, p<0.05) and lower body mass index (16.9kg/m(2) vs 18.4kg/m(2), p<0.01). Among the children with defined airway obstruction, 49% also had lung hyperinflation. Twenty-three children had normal forced expiratory ratios but an increase of the ratio RV/TLC or of RV. When compared with children without lung hyperinflation, the age at diagnosis was significantly lower (3.9+/-1.9years vs 6.2+/-3.1years, p<0.01) and weight slightly lower (31+/-10kg vs 40+/-11kg, p=0.04). In conclusion, the use of plethysmography and thus the evaluation of pulmonary hyperinflation contributed to a better appreciation of the asthmatic phenotype in children.

Malignant melanoma in African-Americans.

Although relatively uncommon, malignant melanoma in African-Americans and other minority ethnic populations represents an aggressive disease highly associated with invasive lesions and a more advanced stage of disease at diagnosis, and consequently with a decreased survival compared with Caucasians. Data on biology of melanoma in African-Americans is very limited, which complicates the analysis of epidemiological information, as well as identification of accurate prognostic variables. This review article explores critical features of melanoma in African-Americans that distinguish it from disease seen in Caucasians, including the clinical presentation, histological patterns, prognostic indicators, and etiology. Emerging data from biologic and genetic studies will also be discussed, raising the possibility that melanoma in pigmented skin may represent molecular distinct cancers that are inherently more aggressive. Improved understanding of the unique manifestations of melanoma in African-Americans, and its underlying tumor biology, will help improve clinical detection, optimize preventative measures through public health education, and potentially lead to the development of novel targeted therapeutic approaches.

The cutaneous epidermal growth factor network: Can it be translated clinically to stimulate hair growth?

The influences exerted by the epidermal growth factor receptor (EGFR) on the skin act at multiple levels, which involve compartments that normally express EGFR. These include the basal and suprabasal layers of the epidermis, sebaceous glands, and the outer root sheath of the hair follicles. The physiological roles of EGFR ensure epidermal renewal and integrity, along with a gatekeeping and function and hair growth stimulation functions. Important cellular functions that are altered during EGF receptor blocking therapy consist of epidermal differentiation, proliferation, apoptosis, and migration, with an overall dominating effect of inducing growth arrest and terminal differentiation of the keratinocytes in the basal layers. The effects of EGFR blockage on the hair cycle include terminal differentiation of the hair follicle, which in certain cases may be associated with trichomegaly. Trichomegaly of the eyelashes may occur as an isolated occurrence or, frequently, as part of a generalized phenomenon that may be associated with the use of the EGFR inhibitors. Molecular changes associated with EGFR blockage are discussed, relevant to their association with hair growth. Modulation of Akt, AP2alpha, CDK4, Notch-1, p27KIP1, and Hedgehog expression are involved in the initiation of the hair cycle and inducement of the anagen phase, followed by proliferation and differentiation of the hair follicles. Epidermal growth factor receptor inhibitors have been developed as therapeutic molecules directed against cancer; in these regimens the knowledge of EGF receptor signaling functions has been translated into significant clinical results. However, among their various collateral effects on the skin, hair growth is observed to occur in certain patients. A particular "wavy" hair phenotype is observed during the pharmacological EGFR receptor blockade, just as in murine transgenic models that carry loss of function of TGF-alpha or EGFR genes. A better characterization of the individual roles pertaining to the EGF family ligands and receptors, has the potential provide new strategies for the management of hair loss.

Persistent hair growth during treatment with the EGFR inhibitor erlotinib.

Medications belonging to the group of epidermal growth factor (EGFR) inhibitors are currently in widespread use for the treatment of epithelial malignancies. Many cutaneous side effects are known to develop as a result of the use of these agents. Trichomegaly is a newly described side effect, consisting of premature maturation (terminal differentiation) of the hair of the eyelashes and the scalp, which is characterized by a hairy phenotype. Although occurrence of the acneiform skin rash is clearly associated with favorable tumor responses and improvement in patient survival during the use of EGFR inhibitors for the treatment of cancer, the significance of trichomegaly is less clear. A review of all published cases is provided, leading to the observation that trichomegaly also developed in patients whose tumors had a positive response to anti-EGFR therapy. The apparent lack of the development of tolerance to this medication effect and, therefore, the continued clinical sign of trichomegaly is in contrast to the time-limited nature of other cutaneous side effects of EGFR inhibitors, such as the classical papulo-pustular rash. The persistence of trichomegaly in some patients brings into question the precise mechanism of this phenomenon and suggests the possibility of using EGFR inhibition therapeutically to stimulate hair growth.

Outcomes of antifungal prophylaxis in high-risk liver transplant recipients.

Antifungal prophylaxis for liver transplant recipients (LTRs) is common among patients considered at high risk of infection, but optimal prophylaxis duration and drug has not been defined. This study aimed to assess the effects of 14 days of antifungal therapy prophylaxis in reducing proven invasive fungal infections (IFI) in high-risk subjects. Eligible subjects who met 2 or more risk criteria were randomized 1:1 to the treatment arms (liposomal amphotericin B or fluconazole) and were followed for 100 days post transplantation for evidence of IFI. The study was designed to enroll 300 subjects, but was closed early for insufficient enrollment. A total of 71 subjects were enrolled and randomized. Two-thirds of subjects completed 14 days of study therapy. Ten subjects developed proven or probable IFI with Candida species (9 subjects) and Cryptococcus neoformans (1 subject); rates were similar in the 2 treatment arms. Eleven subjects died, but no death was attributed to study drug or IFI. In summary, high-risk LTRs tolerated antifungal prophylaxis well, and rates of IFI were lower than previously reported in untreated high-risk LTRs.

Acute scurvy during treatment with interleukin-2.

The association of vitamin C deficiency with nutritional factors is commonly recognized. However, an acute form of scurvy can occur in patients with an acute systemic inflammatory response, which is produced by sepsis, medications, cancer or acute inflammation. The frequency of acute hypovitaminosis C in hospitalized patients is higher than previously recognized. We report the occurrence of acute signs and symptoms of scurvy (perifollicular petechiae, erythema, gingivitis and bleeding) in a patient hospitalized for treatment of metastatic renal-cell carcinoma with high-dose interleukin-2. Concomitantly, serum vitamin C levels decreased to below normal. Better diets and longer lifespan may result a lower frequency of acute scurvy and a higher frequency of scurvy associated with systemic inflammatory responses. Therefore, increased awareness of this condition can lead to early recognition of the cutaneous signs of acute scurvy in hospitalized patients with acute illnesses or in receipt of biological agents, and prevent subsequent morbidity such as bleeding, anaemia, impaired immune defences, oedema or neurological symptoms.

Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease.

Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.

Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting.

The study presented here was performed in order to create a rule that identifies subjects at high risk for invasive candidiasis in the intensive care setting. Retrospective review and statistical modelling were carried out on 2,890 patients who stayed at least 4 days in nine hospitals in the USA and Brazil; the overall incidence of invasive candidiasis in this group was 3% (88 cases). The best performing rule was as follows: Any systemic antibiotic (days 1-3) OR presence of a central venous catheter (days 1-3) AND at least TWO of the following-total parenteral nutrition (days 1-3), any dialysis (days 1-3), any major surgery (days -7-0), pancreatitis (days -7-0), any use of steroids (days -7-3), or use of other immunosuppressive agents (days -7-0). The rate of invasive candidiasis among patients meeting the rule was 9.9%, capturing 34% of cases in the units, with the following performance: relative risk 4.36, sensitivity 0.34, specificity 0.90, positive predictive value 0.01, and negative predictive value 0.97. The rule may identify patients at high risk of invasive candidiasis.

Cardiobacterium hominis endocarditis: Two cases and a review of the literature.

Cardiobacterium hominis, a member of the HACEK group (Haemophilus parainfluenzae, Haemophilus aphrophilus, and Haemophilus paraphrophilus, Actinobacillus actinomycetemcomitans, C. hominis, Eikenella corrodens, and Kingella species), is a rare cause of endocarditis. There are 61 reported cases of C. hominis infective endocarditis in the English-language literature, 15 of which involved prosthetic valve endocarditis. There is one reported case of C. hominis after upper endoscopy and none reported after colonoscopy. Presented here are two cases of C. hominis prosthetic valve endocarditis following colonoscopy and a review of the microbiological and clinical features of C. hominis endocarditis. Patients with C. hominis infection have a long duration of symptoms preceding diagnosis (138+/-128 days). The most common symptoms were fever (74%), fatigue/malaise (53%), weight loss/anorexia (40%), night sweats (24%), and arthralgia/myalgia (21%). The most common risk factors were pre-existing cardiac disease (61%), the presence of a prosthetic valve (28%), and history of rheumatic fever (20%). Of the 61 cases reviewed here, the aortic valve was infected in 24 (39%) and the mitral valve in 19 (31%) patients. The average duration of blood culture incubation before growth was detected was 6.3 days (range, 2-21 days). Complications were congestive heart failure (40%), central nervous system (CNS) emboli (21%), arrhythmia (16%), and mycotic aneurysm (9%). C. hominis is almost always susceptible to beta-lactam antibiotics. Ceftriaxone is recommended by the recently published American Heart Association guidelines. The prognosis of C. hominis native valve and prosthetic valve endocarditis is favorable. The cure rate among 60 patients reviewed was 93% (56/60). For prosthetic valve endocarditis, the cure rate was 16/17 (94%). Valve replacement was required in 27 (45%) cases.

Keloid pathogenesis and treatment.

BACKGROUND: Keloid management can be difficult and frustrating, and the mechanisms underlying keloid formation are only partially understood. METHODS: Using original and current literature in this field, this comprehensive review presents the major concepts of keloid pathogenesis and the treatment options stemming from them. RESULTS: Mechanisms for keloid formation include alterations in growth factors, collagen turnover, tension alignment, and genetic and immunologic contributions. Treatment strategies for keloids include established (e.g., surgery, steroid, radiation) and experimental (e.g., interferon, 5-fluorouracil, retinoid) regimens. CONCLUSION: The scientific basis and empiric evidence supporting the use of various agents is presented. Combination therapy, using surgical excision followed by intradermal steroid or other adjuvant therapy, currently appears to be the most efficacious and safe current regimen for keloid management.