Human herpes virus co-infection is associated with mortality in HIV-negative patients with Pneumocystis jirovecii pneumonia

The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori–Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6?±?18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9?±?20.4. Underlying conditions included hematologic malignancies (n?=?21), vasculitis (n?=?13), and solid tumors (n?=?13). Most patients were receiving systemic corticosteroids (n?=?63) and cytotoxic drugs (n?=?51). Not a single patient received trimethoprim–sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p?=?0.0131), ARDS (p?<?0.0001), shock (p?<?0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p?=?0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5–121.9], p?<?0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.     

Transplantation of Hematopoietic Stem Cells for Primary Immunodeficiencies in Brazil: Challenges in Treating Rare Diseases in Developing Countries

The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. We included data from transplants in 221 patients, performed at 11 centers which participated in the Brazilian collaborative group, from July 1990 to December 2015. The majority of transplants were concentrated in one center (n?=?123). The median age at HSCT was 22 months, and the most common diseases were severe combined immunodeficiency (SCID) (n?=?67) and Wiskott-Aldrich syndrome (WAS) (n?=?67). Only 15 patients received unconditioned transplants. Cumulative incidence of GVHD grades II to IV was 23%, and GVHD grades III to IV was 10%. The 5-year overall survival was 71.6%. WAS patients had better survival compared to other diseases. Most deaths (n?=?53) occurred in the first year after transplantation mainly due to infection (55%) and GVHD (13%). Although transplant for PID patients in Brazil has evolved since its beginning, we still face some challenges like delayed diagnosis and referral, severe infections before transplant, a limited number of transplant centers with expertise, and resources for more advanced techniques. Measures like newborn screening for SCID may hasten the diagnosis and ameliorate patients’ conditions at the moment of transplant.     

Effect of obesity on outcomes in patients undergoing implantation of continuous-flow left ventricular assist devices

The purpose of this study was to analyze the effect of obesity on outcomes after continuous-flow left ventricular assist device (CF-LVAD) implantation. A single-center retrospective analysis was performed on 526 chronic heart failure patients who were implanted with the HeartMate II CF-LVAD (n?=?403) or HeartWare HVAD (n?=?123) between November 2003 and March 2016. Patients were stratified into 4 groups based on BMI: underweight (<?18.5 kg/m², n?=?18, 3.4%), normal-weight (18.5–25 kg/m², n?=?173, 32.9%), overweight (25–30 kg/m², n?=?182, 30.2%), and obese (>?30 kg/m², n?=?153, 33.5%). The underweight group was excluded because of its small sample size. Records were reviewed to determine the incidence of postoperative complications and survival. Survival at 1, 6, 12, and 24 months were similar among normal-weight (91.3, 84.4, 76.3, and 67.6%), overweight (90.4, 80.8, 76.5, and 69.6%), and obese patients (90.7, 74.7, 65.3, and 61.3%, p?=?0.24). Additionally, obesity was not a significant predictor of mortality in Cox proportional hazard models (hazard ratio 0.98, 95% confidence interval 0.766–1.277, p?=?0.13). These findings suggest that appropriately selected obese patients receive similar survival benefit from CF-LVADs compared to non-obese patients, and obesity should not serve as a contraindication to CF-LVAD implantation.     

Which patients should be tested for viruses on bronchoalveolar lavage fluid?

Bronchoalveolar lavage (BAL) is a major diagnostic tool in lung diseases, including viral respiratory infections. We aimed to better define the situations where viral tests should be performed on BAL fluid (BALF). We retrospectively studied all cases where viral tests [immunofluorescence, immunocytochemistry, viral culture, and/or polymerase chain reaction (PCR)] were performed on BALF during a period of 1 year (2008) in our institution. We compared the characteristics of patients with virus-positive versus virus-negative BALF. Of the 636 BALF samples sent to the microbiology laboratory, 232 underwent viral tests. Of these, 70 (30 %) were positive and identified 85 viruses: herpes simplex virus (HSV)-1 (n?=?27), cytomegalovirus (CMV, n?=?23), Epstein–Barr virus (EBV, n?=?18), human herpesvirus (HHV)-6 (n?=?12), respiratory syncytial virus (RSV, n?=?3), rhinovirus (n?=?1), and adenovirus (n?=?1). The variables associated with positive viral tests on univariate analysis were immunosuppression [human immunodeficiency virus (HIV), corticosteroids >10 mg/day for ≥3 weeks, or other immunosuppressive therapy], ground-glass attenuations on computed tomography (CT) scanning, late-onset ventilator-associated pneumonia (VAP), and durations of (i) hospital stay, (ii) intensive care unit (ICU) stay, and (iii) mechanical ventilation before BAL (p?<?0.01 for each comparison). On multivariate analysis, only immunosuppression [odds ratio (OR) 6.4, 95 % confidence interval (CI) [2.8–14.3], p?<?0.0001] and ground-glass attenuations (OR 3.7, 95 % CI [1.8–7.7], p?=?0.0004) remained associated with virus-positive BAL. None of the viral tests performed on BALF for the initial assessment of diffuse infiltrative lung disease (n?=?15) was positive. PCR improved the diagnostic yield of viral tests on BALF by 50 %. Testing for viruses on BALF should be mostly restricted to immunocompromised patients with acute respiratory diseases and/or patients with unexplained ground-glass attenuations on CT scanning.     

Age-related detection and molecular characterization of Cryptosporidium suis and Cryptosporidium scrofarum in pre- and post-weaned piglets and adult pigs in Japan

We investigated the distribution of Cryptosporidium in pigs in Japan by immunofluorescence staining of fecal samples and characterization of isolates by multilocus sequencing. The 344 animals sampled on eight farms included pre-weaned piglets (<1 month old; n?=?55), weaned piglets (1–2 months old; n?=?65), finished pigs (2–4 months old, n?=?105) and of 4–6 months old (n?=?67), sows (n?=?36), and boars (n?=?16). Average prevalence of Cryptosporidium on farms was 32.6 %, ranging from 4.9 to 58.1 %, decreasing with animal age (prevalences of <1 month old, 1–2 months old, 2–4 months old, 4–6 months old, sows, and boars were 27.3, 47.7, 41.9, 22.4, 11.1, 18.8 %, respectively). Piglets (<1 and 1–2 months old) showing signs of diarrhea shed relatively more oocysts (5.28 in average log scale of oocysts per gram) in feces than piglets with normal or loose stools (those of 4.90). Thirty seven successful sequencing of the 18S ribosomal RNA gene among 62 examined samples revealed that all of the identified isolates were Cryptosporidium suis or Cryptosporidium scrofarum, which are generally specific to pigs, and that other species, such as zoonotic Cryptosporidium parvum, were absent. Interestingly, C. suis was frequently found in piglets younger than 2 months old, while C. scrofarum infection was more prevalent in older pigs which also showed increased prevalence of mixed C. suis and C. scrofarum infections. Sequencing of actin gene loci revealed the existence of variants of both Cryptosporidium species in pigs in Japan. Although the number of pigs examined in this study was relatively low, our results suggest that Cryptosporidium infection is widespread among pigs in Japan. In addition, the possibility of age-related specificity and pathogenicity in pig infections is also suggested.     

Home Care Use of Intravenous and Subcutaneous Immunoglobulin for Primary Immunodeficiency in the United States

Purpose

Utilization reports on immunoglobulin (Ig) use for immunodeficiency in the United States (U.S.) have focused on prescribing practices in hospitals. There have been no large-scale reports on Ig use for immune deficiency in the home. We investigated the use of Ig in 3,187 subjects diagnosed with primary immunodeficiency.

Methods

Cross-sectional data on 4,580 subjects in the U.S. receiving Ig in 2011 was obtained from a major home care provider. Demographics, route, dose, and frequency of Ig use by subjects with ICD-9 coded primary immunodeficiencies were analyzed.

Results

Of 4,580 subjects, 3,187 had ICD-9 codes suggesting primary immunodeficiencies; 1,939 (60.8 %) were females and 1,248 (39.2 %) were males, with age ranging from 0 to 95 years. The predominant diagnoses were: common variable immunodeficiency (279.06; n?=?1,764; 55.3 %), hypogammaglobulinemia (279.00; n?=?635; 19.9 %), unspecified immunity deficiency (279.3; n?=?286; 9 %), other selective Ig deficiencies (279.03; n?=?171; 5.4 %), and agammaglobulinemia (279.04; n?=?127; 4 %). 54 % of subjects received Ig by the subcutaneous (SC) route, and 46 % by intravenous (IV) route, with more SC use by older subjects. The mean dose prescribed was 483 mg/kg/month, but less Ig was ordered for subjects on SCIg (409 mg/kg/month), as compared to subjects on IVIg (568 mg/kg/month). A highly significant inverse correlation between increasing age and dosage of Ig ordered was found (P?=?<.0001).

Conclusion

Analysis of home care use of Ig in primary immune deficiency revealed that the SC route was prescribed more than the IV route, especially for older patients. By either method of administration, less immunoglobulin was prescribed for older subjects.     

The Complex Relationship between Human Herpesvirus 6 and Acute Graft-versus-Host Disease

The most frequent manifestation of human herpesvirus 6 (HHV-6) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) is febrile rash, raising the question of its relationship with graft-versus-host disease (GVHD). In this retrospective analysis of 365 patients who underwent allogeneic HSCT, HHV-6 reactivation was significantly associated with cord blood transplantation (hazard ratio [HR], 3.20; P < .0001) and the use of unrelated donors (HR, 2.02; P = .008). On multivariate analysis, previous GVHD was a predictive factor for HHV-6 reactivation (HR, 1.80; P = .01), and previous HHV-6 reactivation was a predictive factor for acute GVHD (HR, 1.66; P = .03). Nineteen patients with no pathological evidence of GVHD later developed severe clinical GVHD (grade III-IV), suggesting the role of HHV-6 as a trigger for severe GVHD. Furthermore, 17 patients without histopathological GVHD demonstrated a significant lymphoid infiltrate suggesting “pure” HHV-6–related manifestations, and these patients could have been spared steroid therapy.     

Acute exercise increases circulating inflammatory markers in overweight and obese compared with lean subjects

The primary aim of the present study was to investigate if overweight and obese compared to lean individuals displayed differences in levels of inflammatory markers in circulation, skeletal muscle (SM) and adipose tissue (AT) after acute exercise. Fifteen lean (BMI: 22.4 ± 2 kg/m²) and 16 overweight or obese (BMI 31.8 ± 3 kg/m²) individuals were included in the study. They completed 120 min of ergometer bicycling at 55–60 % of maximal heart rate. Blood samples were obtained at baseline (T = 0), after 60 (T = 60) and 120 min of exercise (T = 120), and analyzed using an ELISA method. SM and AT biopsies were obtained at T0 and T120, and mRNA expression was investigated using a Real-time RT-PCR method. Circulating IL-6, TNF-α, IL-8, and IL-15 all increased at T = 120 min (p < 0.01). Circulating IL-6 and IL-15 increased in all subjects at T = 120 min (p < 0.01), but only the increase of IL-6 was significantly higher in overweight and obese subjects (p < 0.05), and was positively correlated with body fat percentage (p < 0.01). Circulating IL-8 and TNF-α were increased in overweight and obese (p < 0.05) but not in lean subjects. Acute exercise induced an increase in IL-6 mRNA expression in SM biopsies (p < 0.05). IL-6 as well as adiponectin mRNA expression was increased in AT biopsies (p < 0.05); however, no effect of body weight was found. The findings suggest that the systemic inflammatory response to acute exercise is different in lean compared to overweight and obese subjects, with a more pronounced increase in inflammatory markers (e.g., IL-6, IL-8, and TNF-α) in overweight and obese individuals.     

Differences in Graft-versus-Host Disease Characteristics between Haploidentical Transplantation Using Post-Transplantation Cyclophosphamide and Matched Unrelated Donor Transplantation Using Calcineurin Inhibitors

We assessed differences in presentation and response to therapy in 394 consecutive patients who developed acute or chronic graft-versus-host disease (GVHD) after receiving their first allogeneic transplantation (HSCT) from a 10/10 HLA allele-matched unrelated donor (MUD; n = 179) using calcineurin inhibitors or a T cell-replete haploidentical donor (haplo; n = 215) and post-transplantation cyclophosphamide at our center between 2005 and 2017. The median duration of follow-up for survivors was 52.5 months. The cumulative incidences for grade II-IV and grade III-IV acute GVHD at day 180 post HCT were similar, at 39% and 14%, respectively, for haplo-HSCT compared with 50% and 16% for MUD HSCT (P not significant). Haplo-HSCT recipients had a lower cumulative incidence of moderate to severe chronic GVHD, at 22% (severe, 19%), compared with 31% (severe, 29%) for MUD HSCT recipients (P = .026). The time to onset of moderate to severe chronic GVHD was faster for haplo-HSCT recipients (213 days versus 280 days; P = .011). Among patients with grade II-IV acute GVHD, there was no significant between-group difference in organ involvement, with skin the most affected (75% for haplo-HSCT versus 70% for MUD HSCT), followed by the gastrointestinal tract (71% versus 69%) and liver (14% versus 17% MUD). For chronic GVHD, haplo-HSCT recipients had less involvement of the eyes (46% versus 75% for MUD; P < .001) and of the joints/fascia (12% versus 36%; P = .001). Also for cGVHD patients, haplo-HSCT recipients and MUD HSCT recipients had similar all-cause mortality (22% versus 18%; P = .89), but the former were more likely to be off immunosuppression at 2 years post-HCT (63% versus 43%; P = .03) compared with MUD.     

The healthcare and societal burden associated with influenza in vaccinated and unvaccinated European and Israeli children

Few data exist regarding the healthcare and societal burden of culture-confirmed influenza illness in European and Israeli children. The current analysis describes this burden in vaccinated and unvaccinated children 2–17 years of age. Healthcare and societal burden outcomes were prospectively collected for culture-confirmed influenza illness in three previous randomized studies: a study of live attenuated influenza vaccine (LAIV) versus placebo in children aged <48 months attending day care (N?=?846–973), and studies of LAIV versus inactivated influenza vaccine (IIV) in children aged <72 months with recurrent respiratory infections (N?=?1,609) and in children aged 6–17 years with asthma (N?=?2,211). The incidence of each endpoint among enrolled subjects and subjects with influenza was determined by treatment group and by country. Among subjects with influenza, 57–91 % missed school or day care, 45–90 % used non-antibiotic medications, 29–55 % of parents missed work, 17–55 % used antibiotics, 11–62 % had additional provider visits, and 9–20 % had acute otitis media. Where evaluated, rates of outcomes were generally similar between countries. Among all children enrolled, LAIV recipients missed 324–902 and 150 fewer days of day care per 1,000 children than those of placebo and IIV recipients, respectively; parents of LAIV recipients missed 197–340 and 76 fewer days of work per 1,000 children than those of placebo and IIV recipients, respectively. Influenza illness in European and Israeli children 2–17 years of age resulted in a considerable absenteeism and healthcare utilization that was similar across the countries studied. These data underscore the potential benefits of annual vaccination of children against influenza.     

A retrospective biochemical,molecular, and neurocognitive review of Saudi patients with argininosuccinic aciduria

A retrospective review was compiled of 54 patients with argininosuccinic aciduria who were either identified through the Saudi National Newborn Screening Program or diagnosed clinically from January 2000 to December 2015. The duration of follow-up is from 2 to 19 years. The majority of patients (65%) originated from the central province of Saudi Arabia. The mean patient age at review was 10 years (2–19 years), 92% received an early diagnosis (<28 days of age) and most were symptomatic at the time of the diagnosis (n?=?34). Normal ammonia at diagnosis was reported in 30% of patients, who were detected under the newborn metabolic screen (n?=?5/16). A very high rate of consanguinity was observed in our cohort (98%). Developmental delay was the most detectable long term neurocognitive consequence followed by seizure disorder; 90.7% (n?=?49) and 62.9% (n = 34) respectively. As expected, the severe neonatal form was the major presentation. The most common variant identified in this cohort was the previously reported founder c.1060C > T; p.(Gln354*) nonsense mutation in the ASL gene. In addition, the frequency of hyperammonemia was higher in patients homozygous for c.1060C > T; p.(Gln354*) compared to the other mutations. Interestingly, frequent thrombocytosis with the mean level of 717 × 10⁹/L (range?=?457–1169?×?10⁹/L) was observed in 96% of the patients with no clear explanation.     

Ribotype 027 Clostridium difficile infections with measurable stool toxin have increased lactoferrin and are associated with a higher mortality

We evaluated clinical and diagnostic indicators of severe C. difficile infection (CDI) and their association with poor clinical outcome. A total of 210 patients positive according to PCR (toxin B: tcdB) were included, with patients having a median age of 62 years and a Charlson co-morbidity index (CI) score of 5. Ninety-one percent (n?=?191) were positive by toxigenic culture and 61 % (n?=?129) had stool toxin. Toxin-positive patients had significantly higher fecal lactoferrin (mean 316 μg/g versus 106 μg/g stool; p?<?0.0001). Forty percent of patients (n?=?85) were infected with ribotype 027 and significantly more of these patients had measurable stool toxin (79 % vs. 50 %; p?<?0.0001). The mean fecal lactoferrin was significantly higher for toxin-positive 027 CDI compared with the 027 toxin-negative group (317 vs 60 μg/g; p?=?0.0014). Ribotype 027 CDI with stool toxin showed a higher all-cause, 100-day mortality compared with non-027 with stool toxin (36 % vs 18 %; p?=?0.017). Logistic regression univariate analysis for odds ratio (OR) and p values revealed that age (OR?=?1.1), intensive care unit treatment (OR?=?2.7), CI (OR?=?1.2), 027 CDI (OR?=?2.1), white blood cell count (OR?=?1.0), albumin level (OR?=?0.1), and stool toxin-positive 027 CDI (OR?=?2.5) were significantly associated with 100-day mortality (p?<?0.05). In conclusion, CDI PCR-positive patients with 027 infection and stool toxin have increased lactoferrin and are at an increased risk of death.     

Asthma and Hypogammaglobulinemia: an Asthma Phenotype with Low Type 2 Inflammation

Purpose

Little is known about hypogammaglobulinemia (HGG) in asthma patients. No data are available on the characteristics of adult patients with asthma and HGG.

Methods

We conducted a retrospective monocentric study between January 2006 and December 2012. Asthma patients with a serum immunoglobulin (Ig) quantitative analysis were included and classified into two groups depending on their serum IgG concentration: presence or absence of HGG. Clinical, biological, functional, and radiologic characteristics were compared in univariate and multivariate analysis, using a logistic regression model.

Results

In univariate analysis, asthma patients with HGG (n?=?25) were older (58 years old?±?18 vs 49?±?18, p?=?0.04) and more frequently active or former smokers as compared to patients with normoglobulinemia (n?=?80) (56.0 vs 35.0 %, p?=?0.01). Total IgE?<?30 kUI/L was more frequently observed in patients with HGG (53.0 vs 18.3 %, p?=?0.01). HGG asthma patients had lower fraction of exhaled nitric oxide (p?=?0.02), blood eosinophilia (p?=?0.0009), and presented with more severe composite score for bronchiectasis (p?=?0.01). In multivariate analysis, asthma patients with HGG had increased risk of being smokers [OR?=?6.11 (IC 95 %?=?1.16–32.04)], having total IgE concentration?<?30 kUI/L [OR?=?12.87 (IC 95 %?=?2.30–72.15)], and a more severe composite score of bronchiectasis [OR?=?20.65 (IC 95 %?=?2.13–199.74)].

Conclusion

Asthma patients with HGG are older and more often tobacco smoker than asthma patients without HGG. These patients have low type-2 inflammation markers.

     

Vanishing Bile Ducts in the Long Term after Pediatric Hematopoietic Stem Cell Transplantation

There are no structured studies on liver histology after hematopoietic stem cell transplantation (HSCT). We aimed to prospectively describe the clinicopathologic features of liver disease in the long term after HSCT in an observational, longitudinal study of liver histology in a consecutive cohort of children undergoing allogeneic HSCT. First liver biopsy was performed in presence of abnormal liver function tests and repeated per protocol thereafter. A previously reported semiquantitative score evaluating inflammation, cholestasis, and ductopenia (bile ducts-to-portal tracts ratio ≤ .5) was adopted. Graft-versus-host disease (GVHD) was diagnosed according to standard criteria. We evaluated 131 biopsies taken in 50 HSCTs performed in 47 children (mean age, 9.7 ± 5.2 years). Pre-HSCT chemotherapy was administered in 36 of 50 (72%). GVHD was diagnosed in 17 of 50 (34%). Over time the overall score decreased from a mean of 6 ± 2.7 to 3.25 ± .96 (P < .01), inflammation from 1.22 ± 1.19 to 1 ± 0 (not significant), and cholestasis from 3.9 ± 2.08 to 1.5 ± .58 (P < .01). Ductopenia, found in 113 of 131 biopsies (93%), worsened from .63 ± .35 to .16 ± .14 (P < .01). On multivariate analysis severe ductopenia (ratio ≤ .2) was associated with previous chemotherapy (P?=?.04), in particular with thiotepa, but not with history of GVHD.Vanishing bile duct syndrome after HSCT may be due to drug-induced liver disease. Longer follow-up will reveal whether these patients are prone to late liver-related morbidity and mortality.     

Adenovirus Viremia and Disease: Comparison of T Cell–Depleted and Conventional Hematopoietic Stem Cell Transplantation Recipients from a Single Institution

Adenovirus (ADV) is an important cause of viral mortality in hematopoietic stem cell transplantation (HSCT). Recipients of T cell–depleted (TCD) HSCT are at increased risk for viral infections. We compared the rates and outcomes of ADV viremia and disease between TCD and conventional (CONV) HSCT at our institution. This was an observational study of 624 adult and pediatric recipients of myeloablative HSCT at Memorial Sloan-Kettering Cancer Center between January 1, 2006, and March 11, 2011. Viral cultures and ADV PCR were ordered as clinically indicated. ADV viremia by quantitative PCR assay was defined as 1 or more positive values ≥1,000 copies/mL or 2 or more consecutive positive values. Competing-risk regression analyses were used to identify predictors for ADV viremia. ADV viremia at 1 year after HSCT occurred in 8% of TCD HSCT recipients and in 4.0% of CONV HSCT recipients (P = .041). Among the TCD recipients, ADV viremia was seen in 15% of children, compared with 5% of adults (P = .008). Young age (hazard ratio [HR], 3.0; P < .001) and acute graft-versus-host disease (GVHD) (HR, 3.2; P = .001) were identified as risk factors for ADV viremia. ADV viremia was predictive of mortality (HR, 6.0; P < .001). ADV disease developed in 3.5% of TCD HSCT recipients and in 0.4% of CONV HSCT recipients (P = .022), with an attributable mortality of 27%. Among TCD HSCY recipients, grade II to IV GVHD was a risk factor for ADV disease (HR, 13; P < .001), but age was not. More than 90% of the cases of ADV disease involved a viral load of ≥10,000 copies/mL. Rates of ADV disease were 10-fold greater in TCD HSCT recipients compared with CONV HSCT recipients, predominantly in patients who developed acute GVHD. The benefit of preemptive therapy for an ADV viral load ≥10,000 copies/mL for preventing ADV disease in TCD HSCT recipients should be evaluated in prospective clinical trials.     

Expression of CXCL2 in the Serum and Cerebrospinal Fluid of Patients with HIV and Syphilis or Neurosyphilis

The potential mechanisms for blood–brain barrier damage and the diagnosis of neurosyphilis in HIV patients co-infected with syphilis (HIV-S) are unclear. The aim of the study was to determine the expression of CXCL2 in the serum and cerebrospinal fluid (CSF) of HIV-S patients. A total of 34 HIV patients and 7 controls were enrolled in a HIV clinical cohort for diagnosis of neurosyphilis in Taiwan. Serum and CSF concentrations of CXCL2 were determined by ELISA. Neurosyphilis was defined as a CSF white blood cell count of ≧20 cells/μl or a reactive CSF Venereal Disease Research Laboratory (VDRL). Demographics and medical histories were collected. All the patients with HIV-S were males. Most (80 %) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ≧1:32. The medium age was 37 (range 21–68)?years. The medium CD4 T cell counts at the time of the diagnosis of syphilis were 299 (range 92–434)?cells/μl. Eight patients (24 %) had neurosyphilis based on a reactive CSF VDRL test (n?=?5) or increased CSF white blood cell counts of ≧20 cells/μl (n?=?3). The concentrations of CSF CXCL2 were significantly higher in patients with HIV and neurosyphilis as compared to HIV with syphilis, HIV, and controls (p?=?0.012). There were no significant differences in serum concentrations between the four groups. There was a correlation between CSF CXCL2 concentrations with neurosyphilis (p?=?0.017), CSF white blood cell count (p?=?0.001), and CSF protein levels (p?=?0.005). The CSF level of CXCL2 can be used to distinguish those with or without neurosyphilis in HIV infected patients.     

The Natural History of Children with Severe Combined Immunodeficiency: Baseline Features of the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium Prospective Study 6901

The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n?=?37) and atypical forms (n?=?13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P?=?<0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P?=?<0.0001). Most patients (92 %) were treated with HCT within 1–2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes.     

Thirteen years of antibiotic susceptibility surveillance of Pseudomonas aeruginosa from intensive care units and urology services in the Netherlands

The purpose of this study was the evaluation of trends in the antimicrobial resistance of Pseudomonas aeruginosa from intensive care unit (ICU) patients and urology patients in the Netherlands. From 1998 to 2010, 1,927 consecutive P. aeruginosa isolates from ICU (n?=?1,393) and urology service patients (n?=?534) of 14 university and referral hospitals all over the Netherlands were collected and their susceptibility to relevant antibiotics was determined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Over time, a significant upward trend in the resistance of P. aeruginosa strains collected from ICUs to piperacillin (1.2 % to 10.6 %, p?=?0.0175), piperacillin–tazobactam (1.2 % to 12.1 %, p?=?0.0008), ceftazidime (1.2 % to 7.8 %, p?=?0.0064), cefepime (4.8 % to 6.4 %, p?=?0.0166), imipenem (6 % to 19.1 %, p?<?0.0001), meropenem (8.3 % to 17 %, p?=?0.0022) and ciprofloxacin (13.1 % to 31.2 %, p?=?0.0024) was observed, as was the prevalence of multi-resistance (1.2 % to 8.5 %, p?=?0.0002). For P. aeruginosa isolates from the urology services, the resistance to imipenem increased (4.1 % to 7.8 %, p?=?0.0006) and to ciprofloxacin it decreased (22.4 % to 18.8 %, p?=?0.025). Like in other countries, in the Netherlands, an increase in multi-resistant Gram-negatives is observed, suggesting the presence and dissemination of several mechanisms of resistance. Our findings emphasise the importance of local surveillance for the setting up of local antibiotic guidelines and to support optimal empiric therapy. With the observed increase in multi-resistance, the direct testing of alternative antibiotics like polymyxins and fosfomycin is essential. Our data also illustrate the importance of adequate outbreak control measures.     

Hyperferritinemia is Associated with Serologic Antiphospholipid Syndrome in SLE Patients

Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM)?>?2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)?>?4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6?±?7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p?=?0.003) and lupus anticoagulant (11.3% vs. 29.0%, p?=?0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7?±?369 vs. 30.9?±?17.3 GPI, p?=?0.02) and aCL IgM antibody levels (75.3?±?357.4 vs. 9.3?±?10.3 GPI, p?=?0.02), and marginally lower aCL IgG antibody levels (9.2?±?4.9 vs. 9.7?±?3.9 GPI, p?=?0.096). While the ECLAM score significantly correlated with hyperferritinemia (p?=?0.04), the SLEDAI score was marginally associated with hyperferritinemia (p?=?0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients.