Long-term Infection Risk Research Articles

Treatment of a Mycotic Descending Thoracic Aortic Aneurysm Using Endovascular Stent-Graft Placement and Rifampin Infusion With Postoperative Aspiration of the Aneurysm Sac

Mycotic aortic aneurysms are rare but are associated with high morbidity and mortality due to their propensity for rupture. Traditional therapy consists of open surgical repair with resection and aortic reconstruction or extra-anatomic bypass combined with long-term antibiotic therapy. An 85-year-old male with persistent bacteremia was found to have a descending mycotic aortic aneurysm. Surgical options were discussed and endovascular treatment was recommended with stent-graft placement followed by intra-aortic rifampin infusion. This approach led to resolution of the aneurysm and eradication of bacteremia at 4-month follow-up. By combining traditional surgical strategies with a contemporary endovascular approach, the perioperative mortality and long-term risk of infection associated with mycotic thoracic aneurysms can potentially be decreased.

Information on the internet for asplenic patients: a systematic review.

Asplenic patients in general have poor knowledge about their condition. Patients are increasingly turning to the Internet for their health care information, therefore this is a resource that many asplenic patients will use. The aim of our study was to determine the quality of information on the Internet for asplenic patients. We identified websites by entering "splenectomy OR spleen removal" into 3 Internet search engines on July 28, 2008. The top 50 English-language websites from each search engine were included in our analysis. We evaluated the websites with our own 21-point content scale as well as 4 commonly used quality-assessment tools. All websites were analyzed independently by 2 reviewers. Correlations were made between the quality assessment instruments, content, readability and target audience. We included 89 websites in the study. The mean content score percentage for all websites was 49% (95% confidence interval 44%-54%). The long-term risk of infection was mentioned in 84% of websites, and the need for vaccination was mentioned in 79%. The mean quality assessment tool score was 61%, and the mean reading grade level was 11. Whereas websites on average did not cover most of the information that asplenic patients should receive, the long-term risk of serious infection and the need for vaccination was consistently mentioned. Websites were inconsistent with respect to adhering to standards advocated by the quality assessment instruments we used, and the mean reading grade level was far above what is recommended for patient literature.

Does Anti-Tumor Necrosis Factor-α Therapy Affect Risk of Serious Infection and Cancer in Patients with Rheumatoid Arthritis?: A Review of Longterm Data

Given the important role tumor necrosis factor-α (TNF-α) antagonists play in managing rheumatoid arthritis and the concern for safety during longterm therapy, we reviewed the latest evidence regarding longterm risk of infection and malignancy with TNF-α antagonists. Our objective was to provide clinicians with information that can be used to counsel and monitor patients who may be candidates for biologic therapy for rheumatoid arthritis (RA). Risk is examined in the context of background infection and malignancy rates in RA. Randomized controlled trial (RCT) data and observational studies summarizing the risk of infection and/or malignancy in RA and specific risks associated with the use of anti-TNF-α biologic agents (adalimumab, infliximab, and etanercept) were identified through a PubMed search. Overall, patients with RA appear to have an approximately 2-fold increased risk of serious infection compared to the general population and non-RA controls, irrespective of TNF-α antagonist use. Although data on infection rates with TNF-α antagonist use are contradictory, caution is merited. Recent analyses suggest that the risk of infection is highest within the first year. Regarding malignancy risk, RCT and observational data are also conflicting; how ever, caution is warranted regarding lymphoproliferative cancers in children and adolescents.

Long term risk of infections in Hodgkin lymphoma long‐term survivors

Background Long-term side effects associated with the treatment of Hodgkin’s lymphoma (HL) have frequently been reported during the last decades. Studies have shown increased mortality in HL survivors. Following Hodgkin’s lymphoma, second malignancies (SM) and cardiovascular disease (CVD) are the most common causes of death in individuals treated for HL. This study investigates the incidence of side effects such as SM, CVD and infections in a cohort diagnosed with HL in Sweden between 1965 and 1995. In addition, this study identifies covariate risk factors for late side effects in order to develop strategies that prevent morbidity and mortality in HL survivors. Methods Using the Swedish Cancer Registry (SCR) at the National Board of Health and Welfare and the Multi-Generation Registry at Statistics (MGR) Sweden, we identified 6946 individuals diagnosed with HL between the years 1965 and 1995, and their first degree relatives (FDR) (n=17 858). In addition we identified the malignancies and inpatient care for CVD and infections for the HL cohort and their FDR. The standard incidence ratio (SIR) was calculated for the risk of SM, CVD and infections. For SM and CVD the risk also was stratified and calculated for family history of disease. The Swedish Hodgkin Intervention and Prevention study (SHIP), a prospective study, invited 702 individuals treated for HL at the age of 45 years or younger and who were treated in the region of Skane, Uppsala or Umea. The participants completed a questionnaire and were invited to an out-patient visit to an oncologist with clinical examination and blood tests. Any pathological findings were referred for further investigation. Results An increased risk for SM in HL long-term survivors was observed and seems to increase with the number of FDRs with cancer. There was also an increased risk for inpatient care due to congestive heart failure (CHF) and coronary artery disease (CAD). A family history of CHF and CAD further increased the risk for these diseases. The risk for inpatient care due to infections was increased and remained increased after 20 years or longer. The risk for infections was associated with splenectomy and hypothyroidism. Radiotherapy was an independent risk factor for cardiovascular disease in the cohort of the prospective study. ConclusionLong-term survivors from HL have an increased risk for developing late side effects such as SM, CVD and infections. Since many HL patients are young and the cure rate from the disease is high, it is of great importance to offer focused surveillance programs to selected individuals who are at high risk, e.g. individuals who received radiotherapy as part of their treatment and who have other known risk factors for cardiovascular disease such as hypertension, hypercholesterolemia, family history and smoking.

Long-term clinical outcomes of patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study

AbstractFew data exist on the long-term prognosis of patients with chronic primary chronic immune thrombocytopenia (ITP). We examined the risk of infections, hemorrhage resulting in hospitalization, hematologic malignancies, and total and cause-specific mortality among patients with ITP compared with the general population. We used population-based medical databases to identify 407 patients with primary chronic ITP diagnosed during 1996 to 2007 and 4069 general population members individually matched on age, sex, and comorbidity level. We used Cox regression analysis to estimate rate ratios (RRs) adjusted for age (≤ 60 or > 60 years), sex, calendar year, and level of comorbidity. The adjusted 1-year RR of infection was 4.5 (95% confidence interval [CI], 3.3-6.1) for patients with chronic ITP compared with the general population cohort. The adjusted RR decreased to 1.8 (95% CI, 1.3-2.5) for the second to fifth year of follow-up. The adjusted 5-year RR was 3.2 (95% CI, 1.2-9.0) for hospitalized intracranial hemorrhage, 4.4 (95% CI, 2.3-8.3) for other hospitalized hemorrhages, and 4.7 (95% CI, 1.7-12.7) for hematologic malignancy. The 5-year all-cause mortality RR was 2.3 (95% CI, 1.8-3.0). In summary, primary chronic ITP was associated with substantially increased long-term risk of infections, hemorrhagic episodes requiring hospitalization, hematologic malignancies, and mortality.

Short- and Long-term Risk of Infections as a Function of Group Child Care Attendance

To determine whether the frequency of infections during the first 8 years of life varies according to age at initiation and type of group child care (GCC). Eight-year (1998-2006) prospective cohort study. Families with a newborn living in Quebec in 1998. A representative sample of families (n = 1238) selected through birth registries. Home care compared with small or large GCC during the early (ie, before 2½ years old) or late (3½-4½ years old) preschool period. Maternal reports of children's respiratory tract, ear, and gastrointestinal tract infections during the early preschool, late preschool, and early elementary school (5-8 years old) periods. Compared with children cared for at home, those who started large GCC in the early preschool period had higher rates of respiratory tract infections (incidence rate ratio [IRR], 1.61; 95% confidence interval [CI], 1.27-2.03) and ear infections (IRR, 1.62; 95% CI, 1.19-2.20) during that period but lower rates of respiratory tract infections (IRR, 0.79; 95% CI, 0.66-0.96) and ear infections (IRR, 0.57; 95% CI, 0.37-0.88) during the elementary school years. Children contract infections around the time they initiate large structured group activities. Participation in large GCC before 2½ years old, although associated with increased infections at that time, seems to protect against infections during the elementary school years. Physicians may reassure parents that infections during the first child care years do not lead to a higher overall burden of infections.

Periareolar Mastopexy with FortaPerm

Recurrent ptosis is a common sequel of mastopexy. The use of mesh as an adjunct to the double-skin technique was developed to reduce the incidence of recurrent ptosis. The optimal mesh needs to strike the right balance between persistence, inflammation, biocompatibility, and incorporation without interfering with mammography or presenting a long-term infection risk. This study investigated the ability of a biologic tissue matrix, FortaPerm, to achieve these goals. Women undergoing mastopexy were enrolled in this prospective observational study. The study participants were evaluated at multiple time points for 5 years. Efficacy was assessed primarily by photographic evaluation and secondarily by mammography, patient and physician global assessments, and patient pain assessments. Five women ages 17-41 years were enrolled in this study. At 12 months, 80% of the patients (4/5), and at 5 years, 66% of the patients (2/3) had no asymmetry or ptosis. Mammographic evaluation of the breasts was not affected by the presence of the FortaPerm, and there were no abnormal findings. In two patients, FortaPerm was associated with bilateral seromas associated with extrusion of small amounts of the FortaPerm material in the absence of surrounding inflammation. FortaPerm achieved excellent initial aesthetic outcomes and long-term maintenance of the breast position with no evidence of ptosis 5 years postoperatively for a majority of the patients. FortaPerm did not interfere with mammography, presented no long-term safety concerns, and produced satisfactory results for all patients relative to appearance of the scar as well as shape and firmness of the breasts.

Neurocognitive outcome after endoscopic third ventriculocisterostomy in patients with obstructive hydrocephalus

Obstructive hydrocephalus can be treated with an extracranial shunting system or, when the obstruction is between the posterior third ventricle and the fourth ventricular outflow tracts, by an endoscopic third ventriculocisternostomy (ETV). The placement of an extracranial shunting device entails significant long-term risk of infection and malfunction. This risk has led to the concept that ETV is preferable to shunting. While the long-term cognitive performance of shunted hydrocephalus patients has been extensively examined, the outcome of patients undergoing ETV has been studied only sparsely. Ten adults who had undergone ETV were entered into the study under institutional review board approval. Each patient underwent a neuropsychological testing battery that included testing within the domains of basic attention, verbal memory, visual memory, language, and executive functioning. Aggregate test scores showed a decrease in performance in the domains of memory and executive functioning when compared to normative data. The present study revealed persistent cognitive inefficiencies in memory and executive domains in patients post-ETV intervention. A larger longitudinal study considering the impact of prior shunting, presence of headaches, emotional status, and surgical complications will assist in elucidating the etiology and eventual treatment of these deficits.

Infectious Complications Associated with Alemtuzumab Use for Lymphoproliferative Disorders

Alemtuzumab is an emerging therapy for refractory lymphoproliferative disorders. The associated long-term risks of infection remain poorly defined. From July 2001 through December 2003, all patients who received alemtuzumab for the treatment of lymphoproliferative disorders at 1 institution underwent a retrospective evaluation to document infectious complications until death or end of follow-up in October 2004. Alemtuzumab recipients who underwent allogeneic hematopoietic stem cell transplantation were compared with a concurrent cohort who also underwent allogeneic hematopoietic stem cell transplantation but did not receive alemtuzumab. Twenty-seven patients were identified (21 with chronic lymphocytic leukemia and 6 with plasma cell disorders). The overall mortality was 37%, with 7 of 10 deaths being related to infection. Significant opportunistic infections occurred in 9 patients (43%) with chronic lymphocytic leukemia, including cytomegalovirus, progressive multifocal leukoencephalopathy, adenovirus, toxoplasmosis, and acanthamaebiasis. Thirty nonopportunistic infections in 22 patients (82%) were also identified. The 3 deaths related to nonopportunistic infections all involved Enterococcus species bacteremia. When compared with a concurrent chronic lymphocytic leukemia cohort that underwent allogeneic hematopoietic stem cell transplantation, alemtuzumab recipients had an incidence of cytomegalovirus reactivation of 66.7% (6 of 9 patients), compared with 37% in the non-alemtuzumab group (10 of 27 patients; P = .15), and an incidence of post-transplant opportunistic infections (excluding herpesviruses) of 44.4% (compared with 29.6% in the non-alemtuzumab group; P = .41). Despite the use of herpesvirus and Pneumocystis pneumonia prophylaxis, serious infectious complications occur in patients receiving alemtuzumab for lymphoproliferative disorders. Infectious complications are more varied and diverse in patients receiving alemtuzumab than has been reported in trials to date.

ATG induction therapy: long-term effects on Th1 but not on Th2 responses

Antithymocyte globulin (ATG) induction therapy is associated with an increased long-term risk of infection- and cancer-related death. To analyze long-term effects of ATG induction on lymphocyte function, we prospectively assessed CD4 helper function, B-cell/monocyte and cytokine responses in 84 renal transplant recipients (ATG, n = 44) up to 1 year post-transplant. A PWM-driven allogeneic coculture system was used to assess helper function of CD4+ T cells and T-cell-dependent B-cell responses. SAC I was used for T-cell-independent stimulation of B-cell cultures. In vitro cytokine secretion and serum soluble CD30 (sCD30) were determined by enzyme-linked immunosorbent assay (ELISA). ATG induced a persistent decrease of peripheral blood lymphocyte counts compared with non-ATG treatment because of a predominant decrease of CD4+ T cells (4 months, 1 year; P < 0.0005) which was associated with a decreased CD28 expression (1 year, P = 0.02) and CD4 cell interleukin 2 (IL-2) response (4 months, P < 0.0005). However, Th2 responses (CD4 help, CD4 cell IL-4 and IL-10 responses, sCD30), which proved to be predictive of graft outcome, were not affected, and neither was the secretion of the lymphoma growth factors IL-6 and IL-10 by B cells and monocytes. Our data show that ATG induction therapy in immunological high-risk patients induces a profound long-term decrease in cell counts and Th1 but not Th2 responses of CD4+ T cells which may explain long-term effects on infection and post-transplant lymphoproliferative disease (PTLD) incidence because of inadequate T-cell control.

The Infection Risk of Intrathecal Drug Infusion Pumps after Multiple Refill Procedures

The objective of this study was to evaluate the long-term infection risk from refilling intrathecal drug delivery devices. We studied 25 patients (14 females and 11 males) with intrathecal infusion pumps placed for spasticity (23 patients) and chronic pain (two patients). In this study group there were 890 refill procedures (mean 35.6±20.5; range 8-72 times) performed on an outpatient basis by four different physicians. All refill procedures were performed in a sterile and standardized fashion as suggested by the manufacturer, using manufacturer's approved kits for the refills. During the study period, five patients had recurrent infection of the urinary tract and three patients had recurrent infections of the respiratory tract. At the last pump refill of each patient, residual drug, extracted from the pump reservoir, was sent to a laboratory for aerobic and anaerobic cultures. All cultures, in all pumps, were negative for aerobic and anaerobic bacteria. We conclude that periodic refills of intrathecal implanted pumps do not seem to be a risk factor for infection if standard sterile refill procedures are performed. In this study, it was clear that comorbid infections from other parts of the body do not present as a risk for device contamination.

Thrombotic complications of central venous catheters in cancer patients.

Central venous catheters (CVCs), such as the tunneled catheters and the totally implanted ports, play a major role in general medicine and oncology. Aside from the complications (pneumothorax, hemorrhage) associated with their initial insertion, all of these CVCs are associated with the long-term risks of infection and thrombosis. Despite routine flushing with heparin or saline, 41% of CVCs result in thrombosis of the blood vessel, and this markedly increases the risk of infection. Only one-third of these clots are symptomatic. Within days of insertion, almost all CVCs are coated with a fibrin sheath, and within 30 days, most CVC-related thrombi arise. Aside from reducing the function of the catheter, these CVC-related thrombi can cause postphlebitic syndrome in 15%-30% of cases and pulmonary embolism in 11% (only half of which are symptomatic). Risk factors for CVC thrombosis include the type of malignancy, type of chemotherapy, type of CVC, and locations of insertion site and catheter tip, but not inherited thrombophilic risk factors. Efforts to reduce CVC thrombosis with systemic prophylactic anticoagulation with low-molecular-weight heparin have failed. Low-dose warfarin prophylaxis remains controversial; all studies are flawed, with older studies, but not newer ones, showing benefit. Currently, less than 10% of patients with CVCs receive any systemic prophylaxis. Although its general use cannot be recommended, low-dose warfarin may be a low-risk treatment in patients with good nutrition and adequate hepatic function. Clearly, additional studies are required to substantiate the prophylactic use of low-dose warfarin. Newer anticoagulant treatments, such as pentasaccharide and direct thrombin inhibitors, need to be explored to address this major medical problem.

Local drug delivery to composite tissue allografts.

Unlike visceral solid-organ transplants, composite tissue allografts (CTA) are modules composed of various tissues, each with differing antigenicity, and therefore differing potential for rejection.1 Skin and muscle (and perhaps synovium) are the most antigenic and appear to be most susceptible to rejection, while bone, tendon, cartilage, and neurovascular tissue appear to be less immunogenic and evoke rejection responses of lower magnitude. Although CTA have tremendous potential clinical application for functional and structural reconstruction of major congenital and acquired peripheral tissue defects, these transplants, until recently, have remained one of the last frontiers in clinical organ transplantation because of concerns regarding their risk/benefit ratio.2,3 Two questions address the key issues involved: (1) Can rejection of these highly antigenic tissues be prevented using currently available immunosuppressive regimens with acceptable drug-specific and generalized toxicity? and (2) Will function be restored to a significant degree so as to justify the surgical and immunosuppressive risks involved? The information presented at the Second International Symposium on Composite Tissue Allotransplantation (Louisville, May, 18–19, 2000) has begun to shed some light on the answers to these questions. The recipients of hand transplants in Lyon (two patients), Louisville (one patient), and Guangzhou (two patients) all received a form of antilymphocyte antibody for induction (antithymocyte globulin and/or an interleukin-2 receptor [IL-2R] antagonist), and tacrolimus (FK506), mycophenolate mofetil, and prednisone therapy for maintenance immunosuppression. Despite this clinically acceptable but nonetheless intensive immunosuppressive regimen, akin to that currently utilized for rejection-prone, nonuremic, insulin-dependent diabetics who receive a pancreas transplant,4 the first Lyon patient sustained an episode of acute rejection at 8 weeks and the Louisville recipient developed moderate acute cellular rejection at 6, 20, and 27 weeks posttransplant.5,6 Although all these episodes resolved completely after combination systemic pulse steroid and topical FK506-clobetasol treatment, the transient increase in oral with or without intravenous (IV) prednisone and FK506 doses during and after each rejection episode further increased the already elevated immunosuppressive burden in these patients. Along these lines, the Louisville recipient developed tissue-invasive cytomegalovirus disease at 15 weeks posttransplant, requiring subsequent long-term ganciclovir prophylaxis. These preliminary results suggest that clinical application of CTA is more likely to gain widespread acceptance if the systemic immunosuppressive burden and its attendant long-term risks of infection, malignancy, and drug-specific side effects could be reduced while simultaneously preventing rejection and maintaining function.

Compound anterior cranial base fractures: classification using computerized tomography scanning as a basis for selection of patients for dural repair.

A classification is proposed to organize anterior cranial base fractures systematically according to their location and size. The goal of this study was to determine whether these two variables, irrespective of cerebrospinal fluid (CSF) rhinorrhea, are related to the long-term risk of posttraumatic meningitis and, hence, to standardize decision making concerning surgical repair of associated CSF fistulas. With the aid of high-resolution thin-section coronal computerized tomography (CT) scanning, anterior cranial base fractures were classified into the following four major types: I, cribriform; II, frontoethmoidal; III, lateral frontal; and IV, complex (any combination of the other three types). Fractures with a maximum bone displacement that extended farther than 1 cm in any plane were classified as "large" and those less than 1 cm as "small." The authors used this classification in a study of 48 patients who were treated by conservative (20 patients) or surgical (28 patients) means. The results showed a gradation of risk: the fracture most likely to develop infection was a large cribriform (Type I) and the least likely was a small lateral frontal (Type II). Statistical analysis showed that the trend for an increased infection rate was related to the cumulative effect of three variables in the following order: 1) prolonged duration of rhinorrhea (analysis of variance [ANOVA], p = 0.017); 2) large size of fracture displacement (ANOVA, p = 0.079); and 3) fracture's proximity to the midline (ANOVA, p = 0.015). In this series, microsurgical repair was accompanied by a minimum complication rate. Hence, the authors recommend that patients with fractures that combine the aforementioned variables should be considered to have a high long-term risk of infection and their injury should be surgically repaired as soon as the posttraumatic edema has subsided. This applies to the following fractures: large cribriform (Type I) with transient rhinorrhea lasting 5 to 8 days and large frontoethmoidal (Type II) with prolonged rhinorrhea lasting longer than 8 days. Furthermore, the authors conclude that this classification can improve the management of posttraumatic CSF fistulas of the anterior cranial base and may provide insights into the mechanisms underlying their spontaneous repair and susceptibility to meningitis.

Renal transplantation: current status, complications and prevention.

Renal transplantation is the ideal mode of renal replacement therapy. One-, 5- and 10-year graft survival rates are currently > 85%, 60-70% and 40-50%, respectively. Graft loss in the first year is predominantly due to vascular complications, acute rejection, and death with a functioning graft. Other significant causes of early graft dysfunction are urological complications, delayed graft function and drug-induced nephrotoxicity. Subsequently, graft loss is due to chronic rejection or death with a functioning graft secondary to cardiovascular disease, malignancy and infection. Renal artery stenosis, chronic cyclosporin nephrotoxicity and recurrent disease also contribute to late graft dysfunction. The immunosuppressed renal transplant recipient is at long term risk of infection and neoplasia.