Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later.

INTRODUCTION: For decades, clinicians dealing with immunocompromised and critically ill patients have perceived a link between Candida colonization and subsequent infection. However, the pathophysiological progression from colonization to infection was clearly established only through the formal description of the colonization index (CI) in critically ill patients. Unfortunately, the literature reflects intense confusion about the pathophysiology of invasive candidiasis and specific associated risk factors. METHODS: We review the contribution of the CI in the field of Candida infection and its development in the 20 years following its original description in 1994. The development of the CI enabled an improved understanding of the pathogenesis of invasive candidiasis and the use of targeted empirical antifungal therapy in subgroups of patients at increased risk for infection. RESULTS: The recognition of specific characteristics among underlying conditions, such as neutropenia, solid organ transplantation, and surgical and nonsurgical critical illness, has enabled the description of distinct epidemiological patterns in the development of invasive candidiasis. CONCLUSIONS: Despite its limited bedside practicality and before confirmation of potentially more accurate predictors, such as specific biomarkers, the CI remains an important way to characterize the dynamics of colonization, which increases early in patients who develop invasive candidiasis.

Aesthetic Breast Augmentation Mastopexy Followed by Post-surgical Pyoderma Gangrenosum (PSPG): Clinic, Treatment, and Review of the Literature.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare autoinflammatory neutrophilic ulcerative skin disease, often developing after a trauma or surgical wounds. In the literature there are several reports of post-surgical PG (PSPG) of the breast. The authors of this article experienced an impressive case of PSPG after an aesthetic breast augmentation mastopexy. PSPG is a rare but severe complication in this elective aesthetic surgical procedure. METHOD: A systematic review of the literature was performed, focusing on PSPG after aesthetic breast surgery (augmentation mammoplasty/mastopexy). The online databases Pubmed, Medline, and Cochrane were used and additionally a Google© search was conducted. We compared the data obtained from a systematic literature review to an index case of PSPG after esthetic augmentation mammoplasty. RESULTS: The literature search identified seven articles describing eight cases of PSPG after aesthetic breast surgery. In four of these cases augmentation mammoplasty had been carried out, in two cases mastopexy and in two cases augmentation mammoplasty and mastopexy (augmentation mastopexy). The patient we treated and describe in this paper underwent an augmentation mastopexy outside our clinic. Eight patients suffered from local disease, at the site of surgical wounds, one patient had disseminated disease. Leukocytosis was present in five cases (out of nine). Eight patients had received corticosteroid treatment, one patient refused such treatment. The duration of corticosteroid treatment was on average for 41 days (range 21-60 days). In all cases, the areola had been spared. Complete healing of PSPG was observed on average after 5 months (range 1.5 months-1 year). DISCUSSION: PSPG of the breast after aesthetic breast surgery is rare, but every plastic surgeon should consider this possibility, especially if skin disease develops post-surgery, mimicking wound infection that does not respond to broad-spectrum antibiotic treatment. CONCLUSION: Although the literature does not recommend this step, implant removal is recommended by the authors because bacterial wound infection normally cannot be ruled out definitely in the early stages of disease. Additional surgical intervention should be limited to the absolute necessary and performed only under adequate systemic immunosuppressive therapy. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Surgical complications due to postnatal cytomegalovirus infection in a preterm infant with malrotation.

We report a case of an extremely preterm infant with intestinal malrotation who contracted postnatal systemic cytomegalovirus (CMV) infection with a complicated intestinal evolution requiring repeated surgical interventions and antiviral treatment. This report is to emphasize that prolonged gastrointestinal symptoms in extremely preterm infants fed with non-pasteurized breast milk should lead to suspicion of CMV infection. The importance of preventive measures when feeding very preterm infants with breast milk needs to be considered. Furthermore, the indications for antiviral treatment, in particular in preterm infants, need to be clarified.

Stent graft exclusion of a ruptured mycotic popliteal pseudoaneurysm complicating sternoclavicular joint infection.

A mycotic pseudoaneurysm of the popliteal artery is usually a consequence of septic embolization and often a result of bacterial endocarditis. Conventional treatment is surgical and avoids the placement of foreign material in infected sites. Here we report our treatment of a 59-year-old man who presented with a rupture of a mycotic pseudoaneurysm of the popliteal artery due to septic embolism from sternoclavicular infectious arthritis. Radiological investigations are included. This is the first documented case of septic arthritis complicated by a rupture of a mycotic popliteal false aneurysm and treated using an endovascular procedure. Combining endovascular stent grafts with evacuation of the joint abscess and antibiotic therapy can offer a safe alternative for frail and unstable patients.

Agglutinating Secretory IgA Preserves Intestinal Epithelial Cell Integrity during Apical Infection by Shigella flexneri.

Shigella flexneri, by invading intestinal epithelial cells (IECs) and inducing inflammatory responses of the colonic mucosa, causes bacillary dysentery. Although M cells overlying Peyer's patches are commonly considered the primary site of entry of S. flexneri, indirect evidence suggests that bacteria can also use IECs as a portal of entry to the lamina propria. Passive delivery of secretory IgA (SIgA), the major immunoglobulin secreted at mucosal surfaces, has been shown to protect rabbits from experimental shigellosis, but no information exists as to its molecular role in maintaining luminal epithelial integrity. We have established that the interaction of virulent S. flexneri with the apical pole of a model intestinal epithelium consisting of polarized Caco-2 cell monolayers resulted in the progressive disruption of the tight junction network and actin depolymerization, eventually resulting in cell death. The lipopolysaccharide (LPS)-specific agglutinating SIgAC5 monoclonal antibody (MAb), but not monomeric IgAC5 or IgGC20 MAbs of the same specificity, achieved protective functions through combined mechanisms, including limitation of the interaction between S. flexneri and epithelial cells, maintenance of the tight junction seal, preservation of the cell morphology, reduction of NF-κB nuclear translocation, and inhibition of proinflammatory mediator secretion. Our results add to the understanding of the function of SIgA-mediated immune exclusion by identifying a mode of action whereby the formation of immune complexes translates into maintenance of the integrity of epithelial cells lining the mucosa. This novel mechanism of protection mediated by SIgA is important to extend the arsenal of effective strategies to fight against S. flexneri mucosal invasion.

Functional analysis and structural modeling of human APOBEC3G reveal the role of evolutionarily conserved elements in the inhibition of human immunodeficiency virus type 1 infection and Alu transposition.

Retroelements are important evolutionary forces but can be deleterious if left uncontrolled. Members of the human APOBEC3 family of cytidine deaminases can inhibit a wide range of endogenous, as well as exogenous, retroelements. These enzymes are structurally organized in one or two domains comprising a zinc-coordinating motif. APOBEC3G contains two such domains, only the C terminal of which is endowed with editing activity, while its N-terminal counterpart binds RNA, promotes homo-oligomerization, and is necessary for packaging into human immunodeficiency virus type 1 (HIV-1) virions. Here, we performed a large-scale mutagenesis-based analysis of the APOBEC3G N terminus, testing mutants for (i) inhibition of vif-defective HIV-1 infection and Alu retrotransposition, (ii) RNA binding, and (iii) oligomerization. Furthermore, in the absence of structural information on this domain, we used homology modeling to examine the positions of functionally important residues and of residues found to be under positive selection by phylogenetic analyses of primate APOBEC3G genes. Our results reveal the importance of a predicted RNA binding dimerization interface both for packaging into HIV-1 virions and inhibition of both HIV-1 infection and Alu transposition. We further found that the HIV-1-blocking activity of APOBEC3G N-terminal mutants defective for packaging can be almost entirely rescued if their virion incorporation is forced by fusion with Vpr, indicating that the corresponding region of APOBEC3G plays little role in other aspects of its action against this pathogen. Interestingly, residues forming the APOBEC3G dimer interface are highly conserved, contrasting with the rapid evolution of two neighboring surface-exposed amino acid patches, one targeted by the Vif protein of primate lentiviruses and the other of yet-undefined function.

Evaluation of the anti-arenaviral activity of the subtilisin kexin isozyme-1/site-1 protease inhibitor PF-429242.

The cellular protease subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in the proteolytic processing of the viral envelope glycoprotein precursor (GPC) of arenaviruses, a step strictly required for production of infectious progeny. The small molecule SKI-1/S1P inhibitor PF-429242 was shown to have anti-viral activity against Old World arenaviruses. Here we extended these studies and show that PF-429242 also inhibits GPC processing and productive infection of New World arenaviruses, making PF-429242 a broadly active anti-arenaviral drug. In combination therapy, PF-429242 potentiated the anti-viral activity of ribavirin, indicating a synergism between the two drugs. A hallmark of arenaviruses is their ability to establish persistent infection in vitro and in vivo. Notably, PF-429242 was able to efficiently and rapidly clear persistent infection by arenaviruses. Interruption of drug treatment did not result in re-emergence of infection, indicating that PF-429242 treatment leads to virus extinction.

Neutrophil-derived CCL3 is essential for the rapid recruitment of dendritic cells to the site of Leishmania major inoculation in resistant mice.

Neutrophils are rapidly and massively recruited to sites of microbial infection, where they can influence the recruitment of dendritic cells. Here, we have analyzed the role of neutrophil released chemokines in the early recruitment of dendritic cells (DCs) in an experimental model of Leishmania major infection. We show in vitro, as well as during infection, that the parasite induced the expression of CCL3 selectively in neutrophils from L. major resistant mice. Neutrophil-secreted CCL3 was critical in chemotaxis of immature DCs, an effect lost upon CCL3 neutralisation. Depletion of neutrophils prior to infection, as well as pharmacological or genetic inhibition of CCL3, resulted in a significant decrease in DC recruitment at the site of parasite inoculation. Decreased DC recruitment in CCL3(-/-) mice was corrected by the transfer of wild type neutrophils at the time of infection. The early release of CCL3 by neutrophils was further shown to have a transient impact on the development of a protective immune response. Altogether, we identified a novel role for neutrophil-secreted CCL3 in the first wave of DC recruitment to the site of infection with L. major, suggesting that the selective release of neutrophil-secreted chemokines may regulate the development of immune response to pathogens.

Surgical treatment of ingrown toenail without matricectomy.

BACKGROUND: Partial excision of the nail matrix (matricectomy) is generally considered necessary in the surgical treatment of ingrown toenail. Recurrences may occur, however, and poor cosmetic results are frequently observed. OBJECTIVE: The objective is to present a new surgical procedure for ingrown toenail with complete preservation of the nail matrix. METHODS: Twenty-three patients with ingrown toenail were included in this study. The surgical excision was performed 1 week after the completion of treatment of the initial infection. A large volume of soft tissue surrounding the nail plate was removed under local anesthesia. No matrix excision was performed. RESULTS: Short-term results were excellent. No recurrences or severe complications were observed during the minimum 12-months follow-up period. Cosmetic results were remarkable. CONCLUSIONS: Ingrown toenail results from the compression of the lateral nail folds on the nail plate. This study shows that ingrown toenail can be surgically treated without matricectomy. A large volume of soft tissue surrounding the nail plate should be removed to decompress the nail and reduce inflammation. Cosmetic results are excellent and superior to the classical Emmert plasty. Postoperative nail dystrophies and spicule formation are not observed. The main advantage of this surgical approach is the complete preservation of the anatomy and function of the nail to improve both therapeutic and cosmetic results.

Squamous cell carcinoma in 6 patients with chronic discharging osteomyelitis: Is it really rare?

Introduction: Development of a squamous cell carcinoma (Marjolin's ulcer) is a rare but well-known complication of chronic discharging osteomyelitis. A high index of suspicion and highquality of histopathological examination are paramount in order to make the correct diagnosis. Methods: During a 15-year period (1993 and 2008), patients with long-standing chronic osteomyelitis with clinical symptoms of >1 year of duration, were retrospectively reviewed. Included were patients with histologically confirmed squamous-cell carcinoma associated with chronic wound overlying the site of chronic osteomyelitis. Clinical features and treatment approaches of these patients were analyzed. Results: During the study period, 6 patients were identified (2 women and 4 men) aged 52 to 67 years (mean 59 years). All patients had a long history of chronic discharging osteomyelitis (12, 19, 21, 30, 39 and 40 years), localized in the lower (5 patients) or upper extremitiy (1 patient). All tumors were histologically highly-differentiated squamous-cell carcinomas involving the deep soft tissues and the bone. 5 of 6 patients were initially misdiagnosed as chronic bone infection since bacteria were isolated in wound swabs, including Staphylococcus aureus (n = 3), Escherichia coli (n = 1) and Staphylococcus epidermidis (n = 1). Treatment consisted of major amputation in 4 patients and radical surgical excision in 2 patients refusing amputation. 4 patients were lost to follow-up due to return to their country of origin, the remaining 2 patients were without signs of tumor recurrence (both after major amputation). Conclusion: Malignant transformation of is a rare, but serious complication of long-standing discharging chronic osteomyelitis. All 6 patients were diagnosed after >10 years of persistent or recurrent wounds. It should be particularly suspected in case of a pathological fracture, development of exophytic mass and changes in local pattern of the ulcers itself. Multiple biopsies, including deep soft tissues and bone, are recommended to distinguish between chronic osteomyelitis, pseudoepitheliomatous hyperplasia and highly-differentiated squamous cell carcinoma. Early diagnosis and a team approach (orthopaedic and plastic surgeon) are crucial for optimal management of the patient

Analyse UBM du site de filtration après sclérectomie profonde postérieure modifiée utillisant un tube Ex-PRESS? X-50

Purpose: To study the filtering site using ultrasound biomicroscopy. (UBM) after posterior deep sclerectomy with Ex-PRESS? X-50 implant in patients undergoing filtering surgery.¦Methods: Twenty-six patients that participated in this prospective, non comparative study underwent a posterior deep sclerectomy and an Ex- PRESS? X-50 tube implantation. Clinical outcome factors recorded include: intraocular pressure, number of antiglaucoma medications, best corrected visual acuity (BCVA), frequency and types of complications. Six months postoperatively, an ultrasound biomicroscopy examination was performed.¦Results: Mean follow up was 12.0±3.4 months. Mean IOP decreased from 21 ±5.7 mmHg to 12.4±3 mmHg. At last follow-up examination, 65% of eyes had a complete success and 30% a qualified success. The mean number of antiglaucoma medications decreased from 2.5±1.2 preoperatively to 0.7±1 at the last follow-up postoperatively. BCVA was not changed. 27 complications were observed. On the UBM images, the mean intrascleral space volume was 0.25±0.27 mm3 and no relationship was found between volume and intraocular pressure reduction. We noted in 5/26 (19%) eyes a suprachoroïdal hypoechoic. Low-reflective blebs (L-type) were the most common: 15/26 (58%). No correlation between UBM findings and surgical success was evident.¦Conclusions: Deep sclerectomy with Ex-PRESS? X-50 tube implantation seems an efficient glaucoma surgery. It allows satisfactory IOP reduction with a low number of post operative complications. The advantages of deep sclerectomy with collagen implant are maintained with this modified technique. In both, the same reflective types of filtering blebs are present (high, low, encapsulated and flat). The UBM underlines the three mechanisms of aqueous humor resorption previously identified but no correlation with surgical success can be proved.¦-¦Ce travail de thèse est une analyse par ultrasonographic biomicroscopique (UBM) du site de filtration après sclérectomie profonde postérieure modifiée avec implantation d'un tube Ex- PRESS? X-50.¦Vingt six patients atteints d'un glaucome à angle ouvert, ont participé à cette étude prospective et non-comparative. Le critère d'inclusion est un glaucome à angle ouvert non contrôlé malgré un traitement topique maximal.¦Différents types de chirurgie filtrante sont effectués dans la chirurgie du glaucome dont la trabéculectomie et la sclérectomie profonde.¦L'intervention chirurgicale pratiquée dans cette étude consiste en l'implantation d'un tube Ex-PRESS? X-50 de format défini (3 mm de longueur et 50 μπι de diamètre interne) dans la chambre antérieure,au niveau du trabeculum, sous un volet scléral, ce qui permet le drainage de l'humeur aqueuse vers les espaces sous-conjonctivaux, avec diminution de la pression intraoculaire.¦Cette technique implique uniquement une dissection d'un volet scléral superficiel , sans volet scléral profond comme d'une sclérectomie profonde classique.¦Les modes de fonctionnement de cette sclérectomie profonde modifiée sont explorés par UBM, qui donne des images à haute résolution, semblables à des coupes anatomiques. Le volume de l'espace intrascléral créé artificiellement peut en effet être mesuré et mis en corrélation avec la pression intraoculaire et donc avec le taux de succès. Les différents types d'échogénécité de la bulle de filtration sous-conjonctivale provoquée par la dérivation de l'humeur aqueuse sont également observés. La présence éventuelle d'une filtration supplémentaire au niveau choroïdien est aussi détectée.¦De février 2007 à juin 2008, nous avons suivi chez les vingt six yeux des vingt six patients le volume intrascléral, la filtration sous-conjonctivale et la filtration choroïdienne le cas échéant, de même que l'acuité visuelle, la pression intraoculaire, le nombre de traitement antihypertenseur topique et les complications.¦Les résultats démontrent une réduction de 41 % par rapport à la pression intraoculaire préopératoire, ce qui est statistiquement significatif (p<0.0005). En ce qui concerne l'acuité visuelle, les valeurs demeurent stables. Par ailleurs, le nombre de médicaments antiglaucomateux diminue de façon significative de 2.5 ± 1.2 en préopératoire à 0.7 ± 1.0 au dernier examen (p<0.0005). Le volume de l'espace intrascléral, apparaissant toujours en échographie d'aspect fusiforme, n'est pas corrélé de façon significative avec un meilleur succès chirurgical bien que l'on aperçoive une tendance à une corrélation entre un plus grand volume et une pression intraoculaire plus basse.¦La classification la bulle de filtration se fait selon les 4 catégories de bulle de filtration décrites dans la littérature. La répartition révèle une majorité de type L soit hypoéchogène: 15/26 (58%) et une proportion identique, soit, 4/26 (16%), de bulles hyperéchogènes (type H) et encapsulées (type E); les bulles de filtration plates et hyperéchogènes (type F) sont les moins nombreuses 3/26 (11 %).¦La ligne hyporéflective visible dans 19 % des cas entre la sclère et la choroïde représentant potentiellement un drainage suprachoroïdien, n'est pas associée statistiquement à une meilleure filtration et une pression intraoculaire plus basse mais demeure une troisième voie de filtration, en plus de la filtration sous-conjonctivale et intrasclérale.¦En conclusion, cette technique différente, offrant une plus grande sécurité et des résultats satisfaisants sur l'abaissement de la pression intraoculaire, peut être, dans certains cas, une alternative à la sclérectomie profonde classique ,dont elle partage les mécanismes de filtration objectivés par ultrasonographic biomicrioscopique.

Closure of large intrathoracic airway defects using extrathoracic muscle flaps.

BACKGROUND: Prospective assessment of pedicled extrathoracic muscle flaps for the closure of large intrathoracic airway defects after noncircumferential resection in situations where an end-to-end reconstruction seemed risky (defects of > 4-cm length, desmoplastic reactions after previous infection or radiochemotherapy). METHODS: From 1996 to 2001, 13 intrathoracic muscle transpositions (6 latissimus dorsi and 7 serratus anterior muscle flaps) were performed to close defects of the intrathoracic airways after noncircumferential resection for tumor (n = 5), large tracheoesophageal fistula (n = 2), delayed tracheal injury (n = 1) and bronchopleural fistula (n = 5). In 2 patients, the extent of the tracheal defect required reinforcement of the reconstruction by use of a rib segment embedded into the muscle flap followed by temporary tracheal stenting. Patient follow-up was by clinical examination bronchoscopy and biopsy, pulmonary function tests, and dynamic virtual bronchoscopy by computed tomographic (CT) scan during inspiration and expiration. RESULTS: The airway defects ranged from 2 x 1 cm to 8 x 4 cm and involved up to 50% of the airway circumference. They were all successfully closed using muscle flaps with no mortality and all patients were extubated within 24 hours. Bronchoscopy revealed epithelialization of the reconstructions without dehiscence, stenosis, or recurrence of fistulas. The flow-volume loop was preserved in all patients and dynamic virtual bronchoscopy revealed no significant difference in the endoluminal cross surface areas of the airway between inspiration and expiration above (45 +/- 21 mm(2)), at the site (76 +/- 23 mm(2)) and below the reconstruction (65 +/- 40 mm(2)). CONCLUSIONS: Intrathoracic airway defects of up to 50% of the circumference may be repaired using extrathoracic muscle flaps when an end-to-end reconstruction is not feasible.

Surgical procedure in immunoglobulin G4-related ascending aortitis?

Immunoglobulin G4 (IgG4)-related fibroinflammatory systemic disease accounts for 7% of all noninfectious aneurysms of the thoracic aorta. A patient was admitted with a symptomatic ascending aortic aneurysm and thickened aortic wall (outer/inner diameter 55/45 mm), which was replaced. Probes revealed IgG4-related aortitis associated with a primary tuberculosis infection. Corticosteroid and antituberculosis therapies were used, and the patient's clinical evolution was favorable. The optimal treatment strategy of IgG4-related aortitis, a new entity, remains vague. Inner aortic diameter alone does not justify aortic replacement, but wall thickening may mimic intramural hematoma. In this particular case of IgG4-related aortitis, immunosuppressive treatment alone, as an alternative to a surgical procedure, may be debatable.

Role of the host cell's unfolded protein response in arenavirus infection.

Arenaviruses are enveloped RNA viruses with a nonlytic life cycle that cause acute and persistent infections. Here, we investigated the role of the host cell's unfolded protein response (UPR) in infection of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). In mammalian cells, the endoplasmic reticulum (ER) chaperone protein GRP78/BiP functions as the principal sensor for the induction of the UPR and interacts with three mediators: kinase/endonuclease inositol-requiring protein 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Acute infection with LCMV resulted in a selective induction of the ATF6-regulated branch of the UPR, whereas pathways controlled by PERK and IRE1 were neither activated nor blocked. Expression of individual LCMV proteins revealed that the viral glycoprotein precursor (GPC), but not that of other viral proteins, was responsible for the induction of ATF6. Rapid downregulation of the viral GPC during transition from acute to persistent LCMV infection restored basal levels of UPR signaling. To address a possible role of ATF6 signaling in LCMV infection, we used cells deficient in site 2 protease (S2P), a metalloprotease required for the activation of ATF6. Cells deficient in S2P showed significantly lower levels of production of infectious virus during acute but not persistent infection, indicating a requirement for ATF6-mediated signaling for optimal virus multiplication. In summary, acute LCMV infection seems to selectively induce the ATF6-regulated branch of the UPR that is likely beneficial for virus replication and cell viability, but it avoids induction of PERK and IRE1, whose activation may be detrimental for virus and the host cell.