Prolonged hepatitis A infection in an HIV-1 seropositive patient

Hepatitis A virus (HAV) is a worldwide disease; in most cases, it causes an acute self-limited illness that does not lead to a chronic state. The course of HAV viremia in a homosexual male with human immunodeficiency virus type 1 (HIV-1) and the correlation between HIV and HAV viral load, alanine aminotranferase (ALT) level, and CD4(+) lymphocyte count were investigated during the course of the infection. HAV RNA was detected quantitatively up to 256 days after clinical onset. To our knowledge, this specific case is the first report of a prolonged infection with hepatitis A in a male with HIV-1. The ALT levels decreased gradually; however, 286 days after clinical onset of hepatitis, ALT levels were three times higher than normal values. HIV viral load was not affected by the infection with HAV and CD4(+) cell count was stable during the course of the co-infection. The duration and the high-titer viremia of hepatitis A virus in an immunodeficient patient constitute a serious risk of the spread of hepatitis A within this population. As inactivated HAV vaccine is safe in HIV-positive subjects, it would be wise to establish a strategy of preventive vaccination in this high-risk group.     

Bilateral immediate two-stage breast reconstruction in patients with unilateral breast cancer: Outcomes analysis and risk assessment

IntroductionContralateral prophylactic mastectomy has the potential to decrease the occurrence of cancer and reduce psychological burden. However, it is known that complications after bilateral mastectomy are higher compared with unilateral mastectomy. Our goal was to evaluate outcomes of immediate breast reconstruction in patients undergoing bilateral mastectomy and to compare complication rates between therapeutic and prophylactic sides.Patients and MethodsElectronic medical records of patients with unilateral breast cancer who underwent bilateral mastectomy and immediate reconstruction with expanders were reviewed. Postoperative complications were compared between therapeutic and prophylactic mastectomy sides.ResultsSixty-two patients were analyzed. The overall complication rate after both stages was 23.9% on the therapeutic side and 16.5% on the prophylactic side. Infection was the most common complication on both sides. All infections on the prophylactic mastectomy side were successfully treated with intravenous (IV) antibiotics (salvage rate of 100%), whereas 35.7% of infected tissue expander/implants on the therapeutic mastectomy side were explanted despite treatment.ConclusionCareful counselling of patients undergoing elective contralateral prophylactic mastectomy is essential as complications can develop in either breast after reconstruction.     

Short-term neurobehavioural effects in anaesthetists with low exposure to nitrous oxide

The aim of this study was to assess whether a sample of 37 anaesthetists occupationally exposed only to N2O showed any deterioration in vigilance and/or mood. The anaesthetists were examined with three neurobehavioural tests (Simple Reaction Time and Colour Word Vigilance to measure the vigilance and Mood Rating Scale to evaluate the level of stress and arousal) and underwent N2O biological monitoring (to correlate the test results with the N2O exposure) on the first and on the last day of the work week, before and after work in the operating room. No significant relationship was found between the biological monitoring and the test results. The only significant statistical difference was found between the beginning and the end of each workday in the arousal level, regardless of the result of the biological monitoring.     

Skin and osteoarticular bacterial infections of the diabetic foot. Treatment

MULTIDISCIPLINARY CARE: A multidisciplinary approach is essential. General measures include immobilization of the focus, controlling blood glucose, anticoagulation, and anti-tetanus vaccination. Topical application of growth factors is currently under evaluation. ANTIBIOTIC THERAPY: The antibiotics chosen should diffuse well into bone tissue. Combinations with synergetic or additive effects against Staphylococcus aureus are best. Treatment duration depends on the depth of the ulceration. Two weeks is generally advised for superficial ulcers. For deep ulcers, treatment duration depends on the presence or not of osteitis and the quality of surgical debridement. In case of osteitis, after amputation with a healthy margin, antibiotics can generally be discontinued 2 weeks after surgery. Six weeks are required if the amputation margins do not lie in healthy zones. Finally, if no surgery is attempted, the antibiotic regimen should be continued for 3 months, or even longer, with a risk of failure greater than 50%. The best criterion for successful treatment is the absence of late recurrence. SURGERY: Surgery is an indispensable element in the overall treatment of deep infections and/or osteitis. The operation should be performed as early as possible to improve prognosis. Well-conducted early surgical debridement can prevent the infection from spreading and avoid the need for much more mutilating "salvage" procedures. Vascular surgery can help maintain sufficient blood supply for wound healing and antibacterial defense. Plastic surgery can be very helpful. PREVENTION: A certain number of simple measures help reduce the risk of diabetic foot ulcers. However, many patients, and practitioners, are insufficiently aware of their effectiveness. Prevention and treatment can best be accomplished by a multidisciplinary approach calling upon the endocrinologist and the vascular and orthopedic surgery teams. A carefully planned rehabilitation program using adapted soles, orthesis, orthopedic shoes or prostheses as needed can considerably reduce the frequency of recurrence. The risk of recurrence in a patient wearing adapted footwear is only 26% at 5 years compared with 83% in other cases.     

Nematode ascarosides attenuate mammalian type 2 inflammatory responses

Mounting evidence suggests that nematode infection can protect against disorders of immune dysregulation. Administration of live parasites or their excretory/secretory (ES) products has shown therapeutic effects across a wide range of animal models for immune disorders, including asthma. Human clinical trials of live parasite ingestion for the treatment of immune disorders have produced promising results, yet concerns persist regarding the ingestion of pathogenic organisms and the immunogenicity of protein components. Despite extensive efforts to define the active components of ES products, no small molecules with immune regulatory activity have been identified from nematodes. Here we show that an evolutionarily conserved family of nematode pheromones called ascarosides strongly modulates the pulmonary immune response and reduces asthma severity in mice. Screening the inhibitory effects of ascarosides produced by animal-parasitic nematodes on the development of asthma in an ovalbumin (OVA) murine model, we found that administration of nanogram quantities of ascr#7 prevented the development of lung eosinophilia, goblet cell metaplasia, and airway hyperreactivity. Ascr#7 suppressed the production of IL-33 from lung epithelial cells and reduced the number of memory-type pathogenic Th2 cells and ILC2s in the lung, both key drivers of the pathology of asthma. Our findings suggest that the mammalian immune system recognizes ascarosides as an evolutionarily conserved molecular signature of parasitic nematodes. The identification of a nematode-produced small molecule underlying the well-documented immunomodulatory effects of ES products may enable the development of treatment strategies for allergic diseases.

Parasitic nematodes are associated with almost all groups of vertebrates, and nearly one-third of the human population is infected with these helminths (1). Their omnipresence is in part due to their ability to modulate host immune responses to prevent immune attack and expulsion (2). The elimination of nematode infections has been proposed as a possible cause of the increased incidence of autoimmune disorders and allergic diseases in developed countries (3), based on epidemiological data showing a correlation between the decline in helminth infection and the rise in allergic and autoimmune diseases, including asthma, multiple sclerosis (MS), type 1 diabetes, and inflammatory bowel diseases (IBDs) (4).The administration of live nematodes or their excretory/secretory (ES) products has shown therapeutic effects across a wide range of animal models for these immune disorders (5–8). The US Food and Drug Administration recently approved live helminth administration as an investigational drug for the treatment of immune disorders, and relevant human clinical trials are ongoing (9). Despite mounting evidence that helminths have significant therapeutic potential, we do not yet have a comprehensive understanding of the molecules that underlie their immunomodulatory effects; and, in particular, the possible relevance of low-molecular-weight components of ES products has remained largely unexplored.A wide range of nematodes, including many parasitic species, produce ascarosides, a family of small-molecule signals based on glycosides of the dideoxysugar ascarylose (10). Ascarosides have not yet been identified in any other animal phylum, suggesting that they may be a nematode-specific class of small molecules (SI Appendix, Fig. S1A). The first ascaroside-based signaling molecules were identified in the free-living model nematode Caenorhabditis elegans (11, 12). Ascarosides regulate almost every aspect of C. elegans life history, including diapause (dauer) induction, aging, mate finding, and aggregation (11, 12). Subsequently, ascarosides have been shown to be detected by organisms other than nematodes, such as nematophagous fungi that set traps to capture and digest nematodes (13). The perception of ascarosides is sufficient to trigger trap formation in these fungi, demonstrating their longstanding evolutionary association with nematodes. Furthermore, ascarosides produced by plant-pathogenic nematodes have been shown to trigger innate immune responses in monocot and dicot plants (14). Cumulatively, these findings suggest that ascarosides represent a nematode-specific molecular signature that is recognized and interpreted by nematode predators and hosts across multiple kingdoms.In this study, we collected ES products from the gut-resident, rodent-parasitic nematode Nippostrongylus brasiliensis. Previous studies showed that the administration of N. brasiliensis ES (NES) products fully inhibits the development of airway hyperresponsiveness (AHR) in the ovalbumin (OVA) murine model of asthma (15). Specifically, NES products substantially prevented lung eosinophilia, mucus production, and resistance to airflow. Notably, it was found that heat-treated or proteinase K–treated NES mimicked the full effect of untreated NES products in reducing lung eosinophilia and OVA-specific IgG in serum. Therefore, we hypothesized that the therapeutic effect of NES products may be due to the presence of specific small molecules that may in part be bound to secreted proteins, explaining the activity of heat- or proteinase K–treated NES. To test this hypothesis, we isolated the small molecule fraction of heat-treated NES (small molecule ES [smES]) products via filtration through a 3-kDa filter and found that smES products strongly suppresses OVA-induced allergic immune responses. Parallel chemical analyses of several other mammalian parasitic nematodes confirmed the presence of specific ascarosides in smES products of all tested species. Next, we tested synthetic samples of ascarosides and found that ascr#7, a compound produced by N. brasiliensis and other parasitic species, markedly inhibited the development of allergic airway inflammation, comparable to the full effect of smES products. Mechanistically, we found that ascr#7 administration attenuated IL-33 production from lung epithelial cells and suppressed the proliferation of memory-type IL-5–producing pathogenic T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in the lung, both key drivers for the pathology of asthma. We thus demonstrate that ascarosides have an immunomodulatory role that attenuates OVA-induced allergic inflammation in a murine model.     

Factors associated with mortality in human immunodeficiency virus type 1-infected adults initiating protease inhibitor-containing therapy: role of education level and of early transaminase level elevation (APROCO-ANRS EP11 study). The Antiprotéases Cohorte Agence Nationale de Recherches sur le SIDA EP 11 study

This study attempted to identify factors associated with mortality among human immunodeficiency virus (HIV)-infected adults starting a protease inhibitor (PI)-containing therapy. Among 1155 patients consecutively enrolled in the APROCO study between May 1997 and June 1998, clinical characteristics were as follows: median age, 36 years; median baseline CD4 cell count, 288 cells/mm(3); and median baseline plasma HIV RNA load, 4.4 log(10) copies/mL. After a median follow-up of 27 months, 48 deaths had occurred, of which 44% were related to acquired immune deficiency syndrome. The mortality rate was 2.9% at 12 months. When both data at baseline and data at 4 months after the start of PI therapy were considered, factors independently associated with mortality were (Cox model) low baseline plasma creatinine level, low school education level, low CD4 cell count at 4 months, low hemoglobin level, and elevated hepatic transaminase levels. Thus, social context plus clinical and biologic data, including the 4-month response to treatment, must be considered in treatment of HIV-infected patients.