A Low Incidence of Cytomegalo Virus Infection Following Allogeneic Hematopoietic Stem Cell Transplantation Despite a High Seroprevalence

Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality following allogeneic stem cell transplantation (SCT). We wanted to study if the high sero-prevalence seen in our population translated into a high incidence of CMV infection following SCT. This is a retrospective analysis of patients who underwent allogeneic SCT between January 2008 and December 2012 at our centre. 475 patients underwent allogeneic SCT for malignant (46.5%) and non-malignant (53.5%) haematological disorders. 463 (97.4%) SCT recipients and 403 (84.8%) SCT donors were IgG seropositive for CMV. CMV reactivation within 100 days post SCT was seen in 174 (36.6%) at a median of 41 days (range 10–100) post SCT. Ganciclovir was used in 166 patients (95.4%) for a mean duration of 16 days (range 5–32). 157 patients (90%) responded to therapy. Sixty-six patients (42.3%) had secondary reactivation of the virus. Use of a male donor (p?=?0.000), donor and recipient age?>?15 (p?=?0.005 and 0.000), unrelated donor (p?=?0.000), degree of HLA mismatch (p?=?0.000), occurrence of acute GVHD (p?=?0.000) and steroid refractory acute GVHD (p?=?0.026) were identified as risk factors for CMV reactivation while early neutrophil recovery (<?15 days) was found to be protective (p?=?0.004). On multivariate analysis, male donor (p?=?0.042), degree of HLA mismatch (p?=?0.006), the occurrence of acute GVHD (p?=?0.000) and steroid refractory acute GVHD (p?=?0.031) continued to remain significant. 5-year overall survival was significantly better in patients without CMV reactivation compared to those who developed reactivation of CMV (68.9?±?3.7 vs 58.2?±?4.9% p?=?0.004). The incidence of CMV infection does not seem to be higher despite a high sero-prevalence of CMV. However, patients who developed CMV infection post SCT had inferior outcomes.     

Temporal trajectory of quality of life and its predictors in recipients of hematopoietic stem cell transplantation

This prospective longitudinal study evaluated the temporal trajectory of health-related quality of life (HRQOL) and its associated factors in patients who received hematopoietic stem cell transplantation (SCT) 6 months after transplantation. Eighty-nine adult patients who were admitted to Seoul National University Hospital for SCT were consecutively included in the study. The participants completed three standardized questionnaires: Insomnia Severity Index, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The participants completed the study questionnaires at three time points: before SCT (T1), immediately after SCT (T1), and 6 months after SCT (T3). Immediately after SCT, HRQOL decreased significantly (p?<?0.001), followed by recovery over 6 months. The conditioning regimen for SCT showed no correlation with HRQOL at T2 (p?=?0.283) or T3 (p?=?0.799), with no significant difference in HRQOL between allogeneic and autologous SCT recipients at T2 (p?=?0.829) or T3 (p?=?0.824). Depression (p?=?0.042), pain (p?=?0.023), and appetite loss (p?=?0.004) negatively influenced HRQOL at T1, whereas only pain (p?=?0.048) remained an important factor at T2. Six months after SCT, the two most frequent symptoms, fatigue and financial problems, became major factors (p?=?0.004 and p?=?0.005, respectively). Depression began to play an important role in HRQOL again at T3 (p?=?0.040). These findings demonstrate that SCT recipients need both psychological and medical support to achieve a better HRQOL after SCT.     

Impact of non-transferrin-bound iron (NTBI) in comparison to serum ferritin on outcome after allogeneic stem cell transplantation (ASCT)

The optimal parameters and time points for the measurement of iron overload (IO) in allogeneic stem cell transplantation (ASCT) patients are still under discussion. Hyperferritinemia and IO are poor prognostic factors in ASCT. We hypothesize that non-transferrin-bound iron (NBTI) is possibly a better marker to predict the effect of IO on the outcome than serum ferritin (SF), which however is not specific for IO. The aim of this prospective observational trial was to evaluate the influence of NBTI in comparison to SF on the outcome of ASCT patients [overall survival, bloodstream infections (BSIs), and invasive fungal infections (IFIs)]. We analyzed daily transferrin saturation (TSAT), SF, and NTBI (if TSAT exceeded 70%) in 100 patients who received ASCT during conditioning, and on day 0, +7, and +14 post-ASCT. After a median NTBI level of 0 μmol/l at baseline, the median of the area under the curve (AUC) of NTBI between conditioning and ASCT (d0) increased to 17 μmol*d/l, and between ASCT and day +14 to 56.3 μmol*d/l. Higher NTBI-AUC d0 resulted in a higher risk of BSI (HR 1.042, p = 0.009) and IFI (HR 1.070, p = 0.001) and showed a trend of inferior 1-year survival (65 vs. 76%, p = 0.09). Baseline SF did not influence BSI, but higher levels resulted in more IFI (HR 1.26, p < 0.001). In conclusion, NTBI possibly better predict for a higher risk of bloodstream infections than SF and needs further investigation.     

RABBIT risk score and ICU admission due to infection in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) patients are at increased risk of infection. Aim of the present study was to investigate whether RA patients admitted to an intensive care unit (ICU) due to infection have higher Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk scores compared to control RA patients. Seventy-four RA patients (32.4% male) admitted to an ICU due to infection (from January 2002 to December 2013) and 74 frequency-matched control RA patients (16.2% male) were included in this cross-sectional study. There was strong evidence for a higher RABBIT risk score in ICU patients (median 2.0; IQR 1.3–3.2) as compared to controls (1.3; IQR 0.8–2.0; p < 0.0001). Traditional disease-modifying anti-rheumatic drugs (DMARDs) (82.4 vs 64.9%; p = 0.015) and biological DMARDs (28.4 vs 14.9%; p = 0.012) were more frequently given to RA patients without ICU admission. Glucocorticoid users were more frequently found in the ICU group (51.4 vs 31.1%; p = 0.012). In a multivariable analysis tDMARD use was associated with lower (OR 0.38; 95% CI 0.15–0.93; p = 0.034) and glucocorticoid use with borderline higher odds of ICU admission (OR 2.05; 95% CI 0.92–4.58; p = 0.078). Chronic obstructive pulmonary disease (OR 2.89; 95% CI 1.10–7.54; p = 0.03), chronic kidney disease (OR 16.08; 95% CI 2.00–129.48; p = 0.009), and age category (OR 2.67; 95% CI 1.46–4.87; p = 0.001) were strongly associated with ICU admission. There was a strong trend towards higher odds of ICU admission with increasing RABBIT risk score. Use of tDMARDs was associated with lower odds of ICU admission. In an adjusted analysis, bDMARDs were not associated with ICU admission. COPD, CKD, and age were strong risk factors for ICU admission.     

Enlarged spleen is associated with low neutrophil and platelet engraftment rates and poor survival after allogeneic stem cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome

Primary graft failure can be a cause of early morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), as it leads to a high risk of severe infections and bleeding. Splenomegaly is associated with primary graft failure in patients of myelofibrosis, but the association between splenomegaly and outcomes after HSCT in patients with myeloid malignancies has not been previously evaluated. The aim of this study was to investigate the effect of spleen volume on engraftment kinetics in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We enrolled 85 patients. The median spleen volume was 146 cm³ (quartile 88–201 cm³). The adjusted hazard ratios for neutrophil and platelet engraftments were 0.17 (0.07–0.40, p?<?0.001) and 0.19 (0.05–0.69, p?=?0.011), respectively, for the high-risk group, at a cutoff splenic volume of 320 cm³. Overall survival at 3 years after HSCT was significantly poor in the high-risk group with an adjusted hazard ratio of 13.8 (2.61–72.4, p?=?0.002). Enlarged spleen was associated with low neutrophil and platelet engraftment rates and poor survival after allogeneic HSCT in patients of AML and MDS.     

Bacteremia During Early Post-allogeneic Hematopoietic Stem Cell Transplantation Period: A Single Center Experience

Bacteremia is a significant complication of allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to study bacteremia occurring during early post-transplant period at Bone Marrow Transplantation Unit of Ain Shams University regarding its risk factors and impact on survival. Patients performing allogeneic HSCT were followed up for occurrence of bacteremia. Survival status was assessed at 180 days post-transplant. Bacteremia occurred in 53.3 % of patients. On univariate analysis, CD34 +ve cell dose (P = 0.004), duration of neutropenia (P = 0.018), time interval between day of stem cell infusion and day of neutrophil engraftment (P = 0.043) and > 1 apheresis days (P = 0.040) were associated with higher rates of bacteremia. On multivariate analysis, CD34 +ve cell dose (P = 0.002) and apheresis day number (P = 0.038) remained significant. There was significant difference between patients who developed bacteremia and those who did not regarding overall survival (OS) (P = 0.042). Patients developing bacteremia caused by Gram negative bacteria (GNB) had lower OS than Gram positive bacteria (GPB) (P < 0.001). In conclusion, stem cell dose and apheresis day number influence bacteremia risk. Also, Gram negative bacteremia has negative impact on allogeneic transplant recipient survival rates.     

Independent risk factors for mortality in critically ill patients with candidemia on Italian Internal Medicine Wards

Candida is an increasing cause of bloodstream infection and is associated with significant morbidity and mortality. The aim of our study is to analyze risk factors for short-term mortality in patients with bloodstream Candida spp. infections admitted to Internal Medicine Wards (IMWs). This was a retrospective case–control study between January 2012 and December 2014 from four University Hospitals in Italy, where patients with candidemia dying within 30 days from diagnosis were matched to control cases with candidemia who survived in the same period of time. Two-hundred and fifty cases of candidemia were registered during the 36 months of enrollment. Among these, 112 patients died (45%) within 30 days from the first blood culture’s positivity for Candida spp. At multivariate analysis, septic shock [odds ratio (95% CI) = 2.919 (1.62–5.35), p < 0.001] and concomitant chronic kidney failure [odds ratio (95% CI) = 2.296 (1.07–5.12), p = 0.036] were independent predictors of mortality. Low-dose chronic steroid therapy was protective [odds ratio (95% CI) = 0.461 (0.25–0.83), p = 0.011).     

Infections in patients with aplastic Anemia in Chiang Mai University

Background

Infection is a major complication in aplastic anemia (AA) patients. Primary objectives of this study were to determine the prevalence of infections and to determine types of pathogens associated with infections in patients with AA. Secondary objectives were to evaluate overall survival after infections as well as risk factors of infections in patients with AA.

Methods

The authors retrospectively evaluated the infectious episodes (IEs), type of infections, associated pathogens, and outcomes of infections in patients with AA who were diagnosed and treated at Chiang Mai University between January 2010 and December 2015.

Results

Sixty-seven patients with a median age of 51 years (range, 15–87 years) were enrolled. Forty two patients (62.6%) were severe AA. Median absolute neutrophil count (ANC) was 984 /mm³ (range, 120–5500/mm³). Twenty five patients (37.3%) received antithymocyte globulin plus cyclosporine A, 41 patients (61.1%) received anabolic hormone, and 2 patients (2.9%) underwent allogeneic hematopoietic stem cell transplantation. Overall, 31 IEs were documented in 22 patients (32.8%). The most common microbiologically documented site of infection was bloodstream infection (23.4%) followed by pulmonary infection (14.9%). Culture-negative febrile neutropenia occurred in 12.7%. Common pathogens identified were bacteria (73.9%), mainly gram-negative (52.9%) including Acinetobacter baumannii (23.5%) and Pseudomonas aeruginosa (17.6%). Fungal infections were diagnosed in 21.7% and all were Aspergillus spp. Six patients (9%) died during the study period. All of them died from infection which gram-negative bacteria were most common pathogens (66.7%). Patients with infections had 5-year overall survival of 72% that is significantly less than patients without infection (100%) (p?=?0.0002). Only risk factor that correlates with high probability of infection was ANC?<?500/mm³. (HR 2.29, 95%CI 1.03–7.72, p?=?0.043).

Conclusions

Prevalence of infections in AA patients in Chiang Mai University was 32.8% Bacterial infections especially gram-negative bacteria were the major pathogens. Patients with ANC?<?500/mm³ had higher risk of infections. Infection was the most important cause of death in AA.

     

Prevalence of asymptomatic sexually transmitted infections in HIV-positive men who have sex with men in Germany: results of a multicentre cross-sectional study

Purpose

Sexually transmitted infections (STIs) occur frequently in risk populations. Hereby, the role of screening-programmes remains controversial. Our study aimed to determine the prevalence of STI infections in HIV-positive men-who-have-sex-with-men (MSM).

Methods

We enrolled asymptomatic, HIV-MSM in a prospective cross-sectional study from February to August 2016 at seven German HIV-centres. All subjects were screened for Treponema-pallidum (TP) and hepatitis-B/C-infection. HIV RNA and screening for oral, rectal and urethral colonisation by Chlamydia-trachomatis (CT) and/or Neisseria-gonorrhoeae (NG) was performed. All subjects were asked to complete a sexual-risk-behaviour-questionnaire.

Results

In total, 296 subjects with a median age of 43.2 (36.2–49.5) years were enrolled; 99.3% were on ART for 5.5 (2.3–11.2) years. HIV RNA was < 50 copies/mL in 93.6%. Active syphilis infection was found in 5.0% of all patients, whereas 55.4% had history of infection. HCV seropositivity was found in 33 patients (13.2%) and positive HCV RNA was available in 39.4%. 66/294 (22.5%) showed negative anti-HBs-antibodies, indicating lack of immunity. Overall, 40/296 (13.5%) had positive CT/NG swabs (CT in 8.8%; 7.3% anorectal, 1.7% oropharyngeal, 1.0% urethral and NG in 6.8%; 4.5% anal, 2.0% oropharyngeal, 1.4% urethral). Time since HIV infection < 7 years (OR 2.6 (1.2–5.5); p = 0.012), the use of inhalative nitrites (“poppers”) (OR 2.8 (1.3–5.9; p = 0.008) and reporting unprotected intercourse with > 20 partners within the last 6 months [OR 3.0 (1.2–7.8); p = 0.003] were significantly associated in multivariate analysis.

Conclusion

We found high numbers of asymptomatic syphilis, hepatitis-C and CT/NG infections in HIV-MSM, remarkably in patients with shorter duration of HIV-infection with more sexual partners within last 6 months.

     

Impact of age and comorbidities on the efficacy of FC and FCR regimens in chronic lymphocytic leukemia

CLL is an aging-associated neoplasm with median age at diagnosis >?65 years. Little is known about safety and efficacy of FC/FCR regimens in elderly CLL patients with multiple comorbidities. We retrospectively revised medical records of 90 patients treated with FC/FCR regimens in our clinic. Data on demographic and biological characteristics, comorbidities, response to therapy, and treatment-associated adverse events were analyzed. Compared to FC, FCR yielded higher rates of OR (93.6 vs. 81.4%, p?=?.109) and CR (72.3 vs. 46.5%, p?=?.018). This translated in longer EFS (median 52 vs. 19 months, p?=?<.001) and OS (median 89 vs. 45 months, p?=?.001). Elderly patients (≥?65 years) had more comorbidities and higher median CIRS-G score (7 vs. 4, p?<?.001). However, no association was found between CIRS-G score and survival. Decreased renal function was associated with dismal prognosis in patients treated with FCR.     

Fibrinolysis in patients with a mild-to-moderate bleeding tendency of unknown cause

In more than 50% of patients with a mild-to-moderate bleeding tendency, no underlying cause can be identified (bleeding of unknown cause, BUC). Data on parameters of fibrinolysis in BUC are scarce in the literature and reveal discrepant results. It was the aim of this study to investigate increased fibrinolysis as a possible mechanism of BUC. We included 270 patients (227 females, median age 44 years, 25–75^th percentile 32–58) with BUC and 98 healthy controls (65 females, median age 47 years, 25–75^thpercentile 39–55). Tissue plasminogen activator (tPA-) antigen and activity, plasminogen activator inhibitor type-1 (PAI-1), tPA-PAI-1 complexes, thrombin activatable fibrinolysis inhibitor (TAFI), α2-antiplasmin, and D-dimer were determined. While PAI-1 deficiency was equally frequent in patients with BUC and controls (91/270, 34%, and 33/98, 34%, p = 0.996), tPA activity levels were more often above the detection limit in patients than in controls (103/213, 48%, and 23/98, 23%, p < 0.0001). We found lower levels of tPA-PAI-1 complexes (6.86 (3.99–10.00) and 9.11 (7.17–13.12), p < 0.001) and higher activity of TAFI (18.61 (15.80–22.58) and 17.03 (14.02–20.02), p < 0.001) and α2-antiplasmin (102 (94–109) and 98 (90–106], p = 0.003) in patients compared to controls. Detectable tPA activity (OR 3.02, 95%CI 1.75–5.23, p < 0.0001), higher levels of TAFI (OR 2.57, 95%CI 1.48–4.46, p = 0.0008) and α2-antiplasmin (OR 1.03, 95%CI 1.01–1.05, p = 0.011), and lower levels of tPA-PAI-1 complexes (OR 0.90, 95%CI 0.86–0.95, p < 0.0001) were independently associated with BUC in sex-adjusted logistic regression analyses. We conclude that the fibrinolytic system can play an etiological role for bleeding in patients with BUC.     

Outcomes in patients infected with carbapenem-resistant <Emphasis Type="Italic">Acinetobacter baumannii</Emphasis> and treated with tigecycline alone or in combination therapy

Purpose

Acinetobacter baumannii is a non-fermenting aerobic gram-negative bacteria and one of the important nosocomial pathogens, especially in intensive care units (ICUs). In recent years, multidrug-resistant (MDR) isolates have been an emerging problem, with limited therapeutic options. Tigecycline is a novel antimicrobial, with its in vitro activity against most gram-positive and gram-negative pathogens.

Methods

This is a retrospective study that was conducted in a tertiary care hospital with 550 beds in Ankara, Turkey, from January 2009 to July 2010. Thirty-three patients who had carbapenem-resistant Acinetobacter spp. infections and received tigecycline alone or in combination with other antibiotics for at least 3 days were included.

Results

The median age of the patients was 62 (18–87) years. All of the patients were diagnosed and treated in the ICU. Clinical responses were observed in 23 patients (69.7%). Ten patients (30%) had clinical failure. There was no significant difference between ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) in terms of clinical or microbiological outcome (p > 0.05). The microbiological response rate was 50%. Superinfection was detected in 13 patients (43.3%) and Pseudomonas aeruginosa was the most frequently isolated pathogen. The 30-day overall mortality rate and attributable mortality rates were 57.6 and 24.2%, respectively. The attributable mortality rate was higher in the group in which microbiological eradication was not provided.

Conclusions

Although it is approved by the Food and Drug Administration (FDA) for the treatment of complicated intra-abdominal infections, complicated skin and soft tissue infections, and community-acquired bacterial pneumonia, emerged resistance of Acinetobacter spp. and limited therapeutic options left physicians no choice but to use tigecycline for off-label indications.

     

Significantly elevated foetal haemoglobin levels in individuals with glucose 6-phosphate dehydrogenase disease and/or sickle cell trait: a cross-sectional study in Cape Coast,Ghana

Background

Previously published data have demonstrated that sickle red blood cells produce twice as much reactive oxygen species (ROS) suggesting that co-inheritance of sickle cell disease (SCD) and glucose 6-phosphate dehydrogenase (G6PD) enzymopathy could lead to more severe anaemia during sickling crises. Elevated foetal haemoglobin (Hb F) levels have been shown to have positive modulatory effects on sickling crises and disease outcomes. This study sought to assess how inheritance of G6PD enzymopathy affects the level of Hb F and haemoglobin concentration in adults in steady state.

Methods

This cross-sectional study selected 100 out-patients (41 males and 59 females) visiting the University of Cape Coast hospital, between January, 2016 and May, 2016. Cellulose acetate electrophoresis (pH 8.2–8.6), methaemoglobin reductase test, modified Betke alkaline denaturation methods were used to investigate haemoglobin variants, qualitative G6PD status, and %Hb F levels in venous blood samples drawn from these participants. Data was analysed with GraphPad Prism 6 and SPSS and significance set at p < 0.05.

Results

Forty one percent of the participants demonstrated qualitative G6PD enzymopathy whereas only 10% demonstrated Hb AS type (Sickle cell trait, SCT). 5% of the participants co-inherited SCT and G6PD enzymopathy. %Hb F levels in G6PD deficient males was significantly higher than in G6PD deficient females [(p = 0.0003, 2.696% (males) vs 1.975% (females)], although the %Hb F levels was comparable in non-G6PD deficient individuals. %Hb F levels were significantly elevated in males with SCT only (p < 0.05), or G6PD enzymopathy only (p < 0.0001), or SCT + G6PD enzymopathy (p < 0.0001) compared to males with none of these pathologies even though their respective haemoglobin levels were comparable. Male participants with G6PD enzymopathy + SCT co-inheritance had significantly elevated %Hb F when compared to their counterparts with only G6PD enzymopathy (p < 0.001). Male gender [(p = 0.001, OR: 6.912 (2.277–20.984)] partial defective G6PD enzyme [(p = 0.00, OR: 7.567E8 (8.443E7–6.782E9)] SCT [(p = 0.026, OR: 4.625 (1.196–17.881)] were factors associated with raised %Hb F levels ≥2.5.

Conclusion

The inheritance of G6PD defect and/or SCT significantly elevate %Hb F levels in the steady state even though haemoglobin levels are not affected.

     

Toxicity and efficacy of autologous hematopoietic cell transplantation in elderly patients with aggressive lymphoma: a historical prospective study

High-dose therapy followed by autologous hematopoietic cell transplantation (HCT) prolongs overall survival in patients under 65 years old with relapsed aggressive lymphoma. We aimed to explore the toxicity and efficacy of HCT in patients over 65 years with aggressive lymphoma compared with younger patients. We compared the transplantation outcomes between patients ≥?65 years (n?=?58) and 55–64 years (n?=?44) with chemosensitive aggressive lymphoma (DLBCL, MCL and TCL) that underwent HCT between 1999 and 2016 in the Tel-Aviv Medical Center. The median age was 68 (range, 65–74) and 61 (range, 55–64) years, respectively. There were no differences in the incidences of grade 3–4 mucositis, documented infections and pulmonary complications between the two groups. There was no difference in the incidences of secondary malignancies, relapse (p?=?.26), non-relapse mortality, (p?=?.77) and overall survival (p?=?.53). Multivariate analysis revealed that smoking was a risk factor for non-relapse mortality, while partial remission and >?2 lines of treatment prior HCT were associated with higher risk for relapse. Psycho-socioeconomic score was associated with prolonged hospitalization after HCT and recurrent hospitalizations. We conclude that patients ≥?65 years old with aggressive lymphoma, compared to younger counterparts, have similar transplantation outcome. Improving habits and psychosocial factors may further improve outcomes in these patients.     

Predicting risk factors for varicella zoster virus infection and postherpetic neuralgia after hematopoietic cell transplantation using ordered logistic regression analysis

To identify risk factors for varicella zoster virus (VZV) infection and postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT), we conducted a retrospective chart review of 163 consecutive patients who underwent HCT between November 2004 and July 2014. Overall, the male/female (M/F) ratio was 80/83, median age at HCT was 54 (range 15–69) years, and autologous/allogeneic HCT (auto/allo-HCT) ratio was 71/92. Forty-four patients [M/F, 25/19; median age, 57 (range: 16–68) years; auto/allo-HCT, 26/18] developed VZV infection after HCT. All cases were successfully treated with acyclovir (ACV) or valacyclovir, and there was no VZV-related death. Nine (20%) of the 44 patients [M/F, 5/4; median age, 58 (range: 21–63) years; auto/allo-HCT, 7/2] developed PHN after resolution of zoster. Multivariate ordered logistic analysis identified receiving immunosuppressive therapy at the cessation of ACV [odds ratio (OR) = 74.53; 95% confidence interval (CI) = 6.99–794.32; P = 0.0004] as a risk factor for VZV infection and PHN in allo-HCT recipients. However, in auto-HCT recipients, only advanced age was identified as a risk factor (OR = 1.06, 95% CI = 1.002–1.127, P = 0.0429). Our findings indicate receiving immunosuppressive therapy at the cessation of ACV is a significant risk factor for allo-HCT recipients, while advanced age is a significant risk factor for auto-HCT recipients.     

Dual treatment of acute HCV infection in HIV co-infection: influence of HCV genotype upon treatment outcome

Purpose

With DAAs still only being licensed for chronic HCV infection, the ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal HCV treatment outcome.

Methods

303 HIV-infected patients from 4 European countries with diagnosed acute HCV infection were treated early with pegylated interferon (pegIFN) and ribavirin (RBV) (n = 273) or pegylated interferon alone (n = 30).

Results

All patients were male, median age was 39 years. Main routes of transmission were MSM (95 %) and IVDU (3 %). 69 % of patients were infected with HCV GT 1, 4.3 % with GT 2, 10.6 % with GT 3, 16.1 % with GT 4. Overall SVR rate was 69.3 % (210/303). RVR (p ≤ 0.001), 48-w treatment duration (p ≤ 0.001) and GT 2/3 (p = 0.024) were significantly associated with SVR. SVR rates were significantly higher in HCV GT 2/3 receiving pegIFN and RBV (33/35) when compared with pegIFN mono-therapy (6/10) (94 % vs. 60 % respectively; p = 0.016). In multivariate analysis, pegIFN/RBV combination therapy (p = 0.017) and rapid virological response (RVR) (p = 0.022) were significantly associated with SVR in HCV GT 2/3. In HCV GT 1/4, RVR (p ≤ 0.001) and 48-w treatment duration (p ≤ 0.001) were significantly associated with SVR.

Conclusions

Treatment of AHC GT 2 and 3 infections with pegIFN/RBV is associated with higher SVR rates suggesting different cure rates depending on HCV genotype similar to the genotype effects seen previously in chronic HCV under pegIFN/RBV. With pegIFN/RBV still being the gold standard of AHC treatment and in light of cost issues around DAAs and very limited licensed interferon-free DAA treatment options for chronic HCV GT 3 infection AHC GT 3 patients might benefit most from early interferon-containing treatment.

     

Efficacy and safety of autologous hematopoietic cell transplantation in elderly patients with multiple myeloma: a retrospective national multi-site cohort study

We aimed to test the efficacy and toxicity of autologous hematopoietic cell transplant (HCT) in Multiple Myeloma (MM) patients aged ≥65 years compared to patients aged 60–64. Two hundred twenty consecutive patients (age ≥65, n = 87) with MM aged 60 and above, who underwent HCT as part of an upfront MM treatment, at four Israeli centers between 2000 and 2014 were included. A melphalan dose of 200 mg/m² was more frequent in the 60–64 age group vs. the ≥65 age group (77 vs. 57%, p = 0.002). There were no differences between groups in median day of neutrophil engraftment, incidence of infections, grades 3–4 mucositis, cardiovascular events, or non-relapse mortality at 100 days post HCT (4.7, vs. 5%, p = 0.9). A similar rate of improvement in response level was observed (36, vs. 35%, p = 0.87). At 3 years post HCT progression-free survival (PFS) was higher in the 60–64 age group (42 vs. 29%, p = 0.04); however, it was no longer so after adjustment for disease status prior to HCT (p = 0.49). In a Multivariate analysis, melphalan doses and age did not predict PFS. There was no difference in overall survival (OS) between age groups (p = 0.2). We conclude that toxicity profile, response, PFS, and OS of HCT in aged ≥65 patients with myeloma is similar to patients aged 60–64.     

Gastrointestinal comorbidities in patients with psoriatic arthritis

Comorbidities associated with psoriatic arthritis (PsA) include cardiovascular diseases, diabetes mellitus, and obesity. This study evaluated the association between PsA and common gastrointestinal (GI) diseases. A retrospective study was performed in Israel’s largest health care provider database between 2002 and 2013. 3161 PsA patients were matched for age and sex with 31610 randomly selected patients. We searched these patients’ records for the presence of peptic ulcer disease (PUD), reflux esophagitis, Crohn’s disease, ulcerative colitis, irritable bowel syndrome (IBS) and celiac disease. T-test was used to compare continuous variables and a Chi-square test was used for categorical variables. Multivariate logistic regression models were used to assess the association between PsA and GI comorbidities. PsA was associated with Crohn’s disease (OR 2.4, 95 %CI: 1.75–3.32, p < 0.0001), ulcerative colitis (OR 2.1, 95 %CI: 1.33–3.26, p = 0.001), reflux esophagitis (OR 1.6, 95 %CI: 1.44–1.78, p < 0.0001), PUD (OR 1.5, 95 %CI: 1.31–1.63, p < 0.0001) and IBS (OR 1.4, 95 %CI: 1.01–1.86, p = 0.045). After controlling for known risk factors, the association remained significant between PsA and Crohn’s disease (OR 2.2, 95 %CI: 1.59–3.03, p < 0.0001), ulcerative colitis (OR 1.9, 95 %CI: 1.21–3.00, p = 0.005), reflux esophagitis (OR 1.5, 95 %CI: 1.31–1.63, p < 0.0001), and PUD (OR 1.3, 95 %CI: 1.12–1.47, p < 0.0001). No significant association was found between PsA and celiac disease. In the current study PsA was associated with gastrointestinal morbidities including Crohn’s disease, ulcerative colitis, PUD and IBS. Physicians treating patients with PsA should be aware of these associations.     

A meta-analysis of the clinicopathological characteristics and survival outcomes of inflammatory bowel disease associated colorectal cancer

Purpose

The current study aims to use meta-analytical techniques to compare the clinicopathological characteristics and survival outcomes of inflammatory bowel disease (IBD) associated and sporadic colorectal carcinoma (CRC). Patients with IBD have an established increased risk of developing CRC. There is no consensus, however, on the clinicopathological characteristics and survival outcomes of IBD associated CRC when compared to sporadic CRC.

Methods

A comprehensive search for published studies comparing IBD associated and sporadic CRC was performed. Random effect methods were used to combine data. This study adhered to the recommendations of the MOOSE guidelines.

Results

Data were retrieved from 20 studies describing 571,278 patients. IBD associated CRC had an increased rate of synchronous tumors (OR 4.403, 95% CI 2.320–8.359; p < 0.001), poor differentiation (OR 1.875, 95% CI 1.425–2.466; p < 0.001), and a reduced rate of rectal cancer (OR 0.827, 95% CI 0.735–0.930; p = 0.002). IBD associated CRC however did not affect the frequency of T3/T4 tumors (OR 0.931, 95% CI 0.782–1.108; p = 0.421), lymph node positivity (OR 1.061, 95% CI 0.929–1.213; p = 0.381), metastasis at presentation (OR 0.970, 95% CI 0.776–1.211; p = 0.786), sex distribution (OR 0.978, 95% CI 0.890–1.074; p = 0.640), or 5-year overall survival (OR 1.105, 95% CI 0.414–2.949; p = 0.842).

Conclusions

In this large analysis of available data, IBD associated CRC was characterized by less rectal tumors and more synchronous and poorly differentiated tumors compared with sporadic cancers, but no discernable difference in sex distribution, stage at presentation, or survival could be identified.

     

<Emphasis Type="Italic">C-reactive protein</Emphasis> +1444CT (rs1130864) genetic polymorphism is associated with the susceptibility to systemic lupus erythematosus and C-reactive protein levels

The T rare allele of +1444CT (rs1130864) polymorphism of C-reactive protein (CRP) has been associated with increased CRP levels in some inflammatory conditions, but its role on systemic lupus erythematosus (SLE) susceptibility and on CRP levels in SLE patients remains uncertain. The objective of the study was to evaluate the association between the rs1130864 CRP polymorphism with SLE susceptibility, disease activity, and CRP levels in SLE Brazilian patients. The study enrolled 176 SLE patients and 137 controls. SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI). The rs1130864 CRP polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. SLE patients presented higher body mass index (p = 0.046) and CRP levels (p = 0.017) than controls. The genotype and allele frequencies of patients differed from controls [CC vs. CT = odds ratio (OR) 1.730, 95% confidence interval (CI) 1.068–2.803, p = 0.035; CC vs. TT = OR 3.667, 95% CI 1.410–9.533, p = 0.009; C vs. T = OR 1.883, 95% CI 1.299–2.728, p = 0.001)]. Patients carrying the T allele presented higher CRP levels (p = 0.009), were more frequent Caucasians (p = 0.018), and with no use of immunosuppressive treatment (p = 0.004) than those carrying the C allele. However, the SLEDAI and anti-double-stranded DNA positivity did not differ from those carrying T vs. C allele (p = 0.595 and p = 0.243, respectively). The rs1130864 CRP polymorphism was associated with SLE susceptibility and CRP levels, but not with disease activity, suggesting that this polymorphism may play a role in the pathophysiology of SLE through increasing the CRP that, probably, plays an inflammatory role in SLE pathophysiology.