Management of HIV-infected patients in the intensive care unit

The widespread use of combination antiretroviral therapies (cART) has converted the prognosis of HIV infection from a rapidly progressive and ultimately fatal disease to a chronic condition with limited impact on life expectancy. Yet, HIV-infected patients remain at high risk for critical illness due to the occurrence of severe opportunistic infections in those with advanced immunosuppression (i.e., inaugural admissions or limited access to cART), a pronounced susceptibility to bacterial sepsis and tuberculosis at every stage of HIV infection, and a rising prevalence of underlying comorbidities such as chronic obstructive pulmonary diseases, atherosclerosis or non-AIDS-defining neoplasms in cART-treated patients aging with controlled viral replication. Several patterns of intensive care have markedly evolved in this patient population over the late cART era, including a steady decline in AIDS-related admissions, an opposite trend in admissions for exacerbated comorbidities, the emergence of additional drivers of immunosuppression (e.g., anti-neoplastic chemotherapy or solid organ transplantation), the management of cART in the acute phase of critical illness, and a dramatic progress in short-term survival that mainly results from general advances in intensive care practices. Besides, there is a lack of data regarding other features of ICU and post-ICU care in these patients, especially on the impact of sociological factors on clinical presentation and prognosis, the optimal timing of cART introduction in AIDS-related admissions, determinants of end-of-life decisions, long-term survival, and functional outcomes. In this narrative review, we sought to depict the current evidence regarding the management of HIV-infected patients admitted to the intensive care unit

Campylobacter infection in adult patients with primary antibody deficiency

International audiencePrimary antibody deficiency (PAD) is characterized by a defective immunoglobulin production and recurrent infections, mostly involving respiratory and gastrointestinal tracts. Chronic or recurrent diarrhea is reported in up to 23%. Campylobacter infection is a common cause of infectious diarrhea, reported in 1.2% to 7.5% of patients with common variable immunodefi-ciency (CVID), the most frequent PAD. The aim of this study was to describe Campylobacter infection in patients with PAD included in a large nationwide study and analyze factors associ-ated with susceptibility to this pathogen. The DEFI (DEFicit Immunitaire) study is an ongoing large cross-sectional French multicentric study of adults with PAD, with retrospective collection of clinical data. All patients with a history of bacteriologically documented Campylobacter infection were identified, and clinical data were collected for each episode. Factors associated with recurrent infection were assessed as oddsratio (OR) and 95% confidence interval (CI), calculated by means of simple regression analysis. In patients with available material, strains of each episode were characterized using molecular analysis and compared (Table E1, available in this article’s Online Repository at www.jaci-inpractice.org). A com-parison of immunodeficiency-related characteristics of patients with and without Campylobacter infection was performed in the homogeneous group of patients with CVID. The control group included patients with CVID from DEFI centers who confirmed that patients did not develop Campylobacter infection after enrollment (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). After correction for multiple comparisons, P<.016 was considered significant. Since 2004, 790 patients with PAD were included in the DEFI study, and 51 presented with Campylobacter infection (6.5%). Medical chart was available for review in 45 patients. Characteristics of these patients at the time of enrollment in the DEFI study are detailed in Table E2 (available in this article’s Online Repository at www.jaci-inpractice.org). A total of 97 episodes were recorded (Table I). The overall distribution of Campylobacter species was unremarkable. Antimicrobial susceptibility testing revealed a higher resistance rate than in the general population for each antibiotic tested (see Figure E2, available in this article’s Online Repository at www.jaci-inpractice.org). A comorbidity was present in 55% of Campylobacter episodes, and a coinfection by other enteropathogens in 10%. Most patients were receiving concomitant therapy at the time of episode. One patient with end-stage cirrhosis died with Campylobacter bacteremia. Overall, bacteremia was observed in 24 episodes (13 patients) and was associated with extraintestinal complication in 10 episodes. Nineteen patients (42%) presented with recurrent (2-11) episodes. Factors associated with recurrent episodes were the presence of comorbidity (OR, 3.7 [95% CI, 1.1-13.1]) and undetectable serum IgA (OR, 8.6 [95% CI, 1.1-21.2]). None of these factors remain significant in multivariate analysis. A mo- lecular study of a subset of 18 strains from 5 patients with recurrent infections demonstrated that all strains were different, even when the antimicrobial susceptibility testing was similar and when the episodes occurred closely over time (Figure E3, available in this article’s Online Repository at www.jaci-inpractice.org). Compared with 288 patients with CVID without Campylobacter infection, patients with CVID with Campylo-bacter infection presented a higher prevalence of consanguinity and a more severe CVID phenotype, with more frequent disease- related complications, lower serum immunoglobulin levels, lower B and natural killer (NK) cells, and a trend for lower naive CD4þT cell at the time of enrollment in the DEFI study (Table II). This study is the first description of a large series of patients with PAD and Campylobacter infection. The 6.5% prevalence was probably underestimated because of the retrospective nature of the clinical data collection. In this population, symptoms were mostly restricted to an isolated, frequently severe, chronic watery diarrhea, with associated malnutrition, leading to repeated hospitalizations and impaired quality of life. Other digestive symptoms and fever were less frequent than those observed in the general population. In contrast, bacteremia and extra- digestive localizations were more frequent (25% vs 0.15% to 2%, and 22% vs 7%, respectively). Despite frequent hospitalizations, the overall prognosis was good. Recurrence rate was high (42%) compared with 1.2% in the general population, and was associated with extraintestinal comorbidity and unde- tectable IgA level in univariate analysis. Although limited by the number of available strains, molecular profiles of strains from patients with recurrent infections were all different. Thus, we could hypothesize that reinfection is more likely than persistent colonization, although colonization with multiple strains cannot be excluded. Conditions associated with the occurrence of Campylobacter infection were described in an analysis restricted to a large ho- mogeneous group of 325 patients with CVID. The present data suggest that hypochlorhydria, either proton pump inhibitor (PPI)-induced or associated with autoimmune gastritis, might play an important role in the pathogenesis of this infection. Almost all CVID-associated complications, particularly liver and gastrointestinal disease, were more frequent in patients with Campylobacter infection. A more severe immune deficiency at CVID diagnosis, with a lower serum immunoglobulin level, was also observed. Even in patients with immunoglobulin replacement therapy, IgM and IgA levels remain very low. IgA and IgM, almost absent in immunoglobulin batches, are more important than IgG in Campylobacter immunity. B-cell and specifically switch memory B-cell deficiency was also more severe in patients with CVID with Campylobacter infection than in patients without Campylobacter infection. This is in line with the high prevalence of Campylobacter infection observed in Good syndrome and X-linked agammaglobulinemia, 2 conditions associated with no circulating B cells (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). B cells are also known to be important for the dialogue between the immune system and gut microbiota, whose composition is important for Campylobacter immunity. T cells may also play an important role, with a trend for decreased naive T cells. Indeed, 15 patients (40%) presented with a severe associated T-cell defect and could be considered as late-onset combined im-munodeficiency (data not shown). In patients with PAD, Campylobacter infection is quite frequent and seems to be related to various factors adding up together: severity of the immune deficiency, PAD complication, and associated antibiotics, immunosuppressive therapies, and PPI. It is characterized by a high frequency of recurrence and bacteremia. Recurrence is associated with the presence of comorbidity and IgA defect, and turned out to be due to rein- fection more than to persistent colonization, suggesting a specific susceptibility despite immunoglobulin substitution

Campylobacter infection in adult patients with primary antibody deficiency

International audienceNo abstract availabl

Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study

Background Activated phosphoinositide 3-kinase δ syndrome (APDS) 2 (p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency [PASLI]–R1), a recently described primary immunodeficiency, results from autosomal dominant mutations in PIK3R1, the gene encoding the regulatory subunit (p85α, p55α, and p50α) of class IA phosphoinositide 3-kinases. Objectives We sought to review the clinical, immunologic, and histopathologic phenotypes of APDS2 in a genetically defined international patient cohort. Methods The medical and biological records of 36 patients with genetically diagnosed APDS2 were collected and reviewed. Results Mutations within splice acceptor and donor sites of exon 11 of the PIK3R1 gene lead to APDS2. Recurrent upper respiratory tract infections (100%), pneumonitis (71%), and chronic lymphoproliferation (89%, including adenopathy [75%], splenomegaly [43%], and upper respiratory tract lymphoid hyperplasia [48%]) were the most common features. Growth retardation was frequently noticed (45%). Other complications were mild neurodevelopmental delay (31%); malignant diseases (28%), most of them being B-cell lymphomas; autoimmunity (17%); bronchiectasis (18%); and chronic diarrhea (24%). Decreased serum IgA and IgG levels (87%), increased IgM levels (58%), B-cell lymphopenia (88%) associated with an increased frequency of transitional B cells (93%), and decreased numbers of naive CD4 and naive CD8 cells but increased numbers of CD8 effector/memory T cells were predominant immunologic features. The majority of patients (89%) received immunoglobulin replacement; 3 patients were treated with rituximab, and 6 were treated with rapamycin initiated after diagnosis of APDS2. Five patients died from APDS2-related complications. Conclusion APDS2 is a combined immunodeficiency with a variable clinical phenotype. Complications are frequent, such as severe bacterial and viral infections, lymphoproliferation, and lymphoma similar to APDS1/PASLI-CD. Immunoglobulin replacement therapy, rapamycin, and, likely in the near future, selective phosphoinositide 3-kinase δ inhibitors are possible treatment options

Splenectomy and/or cyclophosphamide as salvage therapies in thrombotic thrombocytopenic purpura: the French TMA Reference Center experience: SALVAGE THERAPIES IN SEVERE TTP

BACKGROUND: The objective was to assess the efficacy and safety of splenectomy and cyclophosphamide as salvage therapies in severe thrombotic thrombocytopenic purpura (TTP).STUDY DESIGN AND METHODS: During a 10-year period, patients who did not improve with plasma exchanges, steroids, vincristine, and/or rituximab were considered for splenectomy or cyclophosphamide. Patients with a documented severe (&lt;10% of normal value) acquired ADAMTS13 deficiency are reported here. RESULTS: Eighteen patients with a severe acquired ADAMTS13 deficiency required a salvage therapy. Thirteen patients had a splenectomy 19 (interquartile range [IQR], 10-51) days after TTP diagnosis. One patient died the day after splenectomy. The remaining patients improved platelets (PLTs) until Day 6, along with a rapid and major lactate dehydrogenase improvement. Six patients, however, subsequently experienced a transient worsening. Durable PLT count recovery in survivors was observed within 13 (IQR, 11.5-25.5) days. Postoperative complications included thromboembolic events (two cases) and infections (five cases). Five patients received pulses of cyclophosphamide 12 (IQR, 12-15) days after TTP diagnosis. All patients recovered PLTs 10 (IQR, 9-24) days after the first pulse and two experienced a transient worsening. Three patients experienced infections. Three relapses occurred 5 months, 2.5 years, and 4.5 years after splenectomy and one relapse occurred 3.5 years after cyclophosphamide. After a 2.5 (IQR, 0.75-6.2)-year follow-up, the overall survival was 94%. CONCLUSION: Cyclophosphamide and splenectomy provide comparable high remission rates in severe TTP with acceptable side effects and should be considered in the more severe patients who do not improve with other therapies

A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode

Persistent risk of adult T-cell leukemia/lymphoma after neonatal HTLV-1 infection through exchange transfusion

A 36-year-old Caucasian male presented with adult T-cell leukemia/lymphoma (ATL). HTLV-1 contamination was attributed to a neonatal exchange transfusion. Remission was achieved but 11 years later he presented with symptoms suggesting ATL relapse. Molecular studies of T-cell clonality and virus integration sites revealed a clonal disease, distinct from the first tumor