Cytomegalovirus Reactivations in Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Matched and Haploidentical Donors with Post-Transplantation Cyclophosphamide.

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections. We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type. Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies.

Torque Teno Virus plasma DNA load: a novel prognostic biomarker in CAR-T therapy.

Torque Teno Virus (TTV) is a single-stranded circular DNA virus which has been identified as a surrogate marker of immune competence in transplantation. In this study we investigated the dynamics of plasma TTV DNAemia in 79 adult patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory large B-cell lymphoma, also evaluating the impact of TTV on immunotoxicities, response and survival outcomes. After lymphodepleting therapy, TTV DNA load was found to decrease slightly until reaching nadir around day 10, after which it increased steadily until reaching maximum load around day 90. TTV DNA load < 4.05 log10 copies/ml at immune effector cell-associated neurotoxicity syndrome (ICANS) onset identified patients at risk of progressing to severe forms of ICANS (OR 16.68, P = 0.048). Finally, patients who experienced falling or stable TTV DNA load between lymphodepletion and CAR-T infusion had better progression-free survival than those with ascending TTV DNA load (HR 0.31, P = 0.006). These findings suggest that TTV monitoring could serve as a surrogate marker of immune competence, enabling predictions of CAR-T efficacy and toxicity. This could pave the way for the development of TTV-guided therapeutic strategies that modulate clinical patient management based on plasma TTV load, similar to suggested strategies in solid organ transplant recipients.

Enhanced recovery after bariatric surgery (ERABS) protocol implementation in a laparoscopic center.

INTRODUCTION: Enhanced recovery after bariatric surgery (ERABS) protocols consist of a combination of several preoperative, intraoperative and postoperative methods for the management of the surgical patient. The aim of this study was to evaluate the impact of the ERABS protocol on length of hospital stay (LOS) and postoperative complications. MATERIAL AND METHODS: Retrospective study of patients who underwent elective Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between 2015 and 2018. From 2015 to 2017, patients received traditional management (pre-ERABS group). Those who underwent surgery during 2018 were managed with our ERABS protocol (ERABS group). The primary outcome was LOS. Secondary outcomes were readmission rate and 30-day postoperative complications. RESULTS: A total of 200 patients who received RYGB and SG between 2015 and 2018 were retrospectively analyzed; we included 120 patients in the pre-ERABS group and 80 in the ERABS group. The median LOS was four days [2-49] in the pre-ERABS group, as compared with two days [1-26] in the ERABS group (p < .0001). No significant differences were found in postoperative complication rates, readmissions, and mortality. CONCLUSION: Implementation of the ERABS protocol is related to a better postoperative recovery and allows an early discharge without increasing postoperative complications, readmissions or mortality.

Adjuvant Effect of Titanium Brushes in Peri-Implant Surgical Treatment: A Systematic Review.

BACKGROUND: the prognosis of peri-implant surgery can be affected by poor decontamination of the implant surface, which could be improved with the use of titanium brushes. The objectives of this systematic review were to evaluate the effectiveness of titanium brushes in the decontamination of the implant surface in terms of plaque index, probing depth, bleeding on probing and bone loss/gain; as well as its effectiveness according to the type of peri-implant bone defect. METHODS: an electronic search was carried out in the PubMed, Scopus, Cochrane and Embase databases, as well as a manual search. The search strategy included four keywords: "Peri-implantitis", "Periimplantitis", "Implant Surface Decontamination" and "Titanium Brush". Randomized controlled studies published in the last 10 years were included and systematic reviews, in vitro studies and animal studies were excluded. RESULTS: 142 references were found, from which only four articles met the inclusion criteria. All of the studies included in the present review reported beneficial results in terms of probing depth, gingival index and radiographic bone loss and gain after implant surface decontamination adjuvated by titanium brushes. CONCLUSIONS: titanium rotary brushes show improvements in the evolution and prognosis of peri-implant surgery, although more long-term studies are needed to draw more solid conclusions.

Common seasonal respiratory virus infections in allogeneic stem cell transplant recipients during the SARS-COV-2 pandemic.

The SARS-COV-2 pandemic has led to strict and generalized transmission prevention measures that may have changed the epidemiological landscape of common seasonal respiratory virus (CSRV). Through a prospective CSRV survey program conducted from 2016 onwards in allogeneic stem cell transplant (allo-HSCT) recipients with respiratory symptoms, we aimed to analyze and compare the epidemiology and characteristics of CSRV over three consecutive periods [from February 1 to September 30 of 2018 (P1), 2019 (P2), and 2020 (P3)]. CSRV screening was performed through multiplex PCR assays during the study period. We identified 188 consecutive allo-HSCT recipients with 406 episodes screened for CSRV during the study period, of which 147 developed 300 CSRV. In P1 and P2 we diagnosed 115 (38.3%) and 145 (48.3%) CSRV episodes, respectively, whereas in P3 only 40 (13.3%) episodes were detected (p < 0.001). During P3, we observed a reduction of 80.2% in Ev/Rh, 93.3% in RSV, 80% in hIV, 96.3% HPIV, 68.4% in hMPV, 77.7% in ADV, 100% in HBoV, and 53.6% in HCoV as compared to P1 and P2. Consequently, we also observed a decline in absolute numbers of lower respiratory tract disease (68.1%), co-infections (91.7%), and hospitalizations (72.6%) during P3. We diagnosed SARS-COV-2 in nine allo-HSCT recipients, representing 23% of all CSRV detections in that period. In conclusion, we provide evidence of a significant drop in CSRV circulation during the SARS-COV-2 pandemic in our allo-HSCT recipients, indicating that prevention measures in the general population are highly effective in reducing CSRV prevalence and its complications in immunocompromised patients.

Adoptive transfer of ex vivo expanded SARS-CoV-2-specific cytotoxic lymphocytes: A viable strategy for COVID-19 immunosuppressed patients?

Cellular and humoral response to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is on focus of research. We evaluate herein the feasibility of expanding virus-specific T cells (VST) against SARS-CoV-2 ex vivo through a standard protocol proven effective for other viruses. The experiment was performed in three different donors' scenarios: (a) SARS-CoV-2 asymptomatic infection/negative serology, (b) SARS-CoV-2 symptomatic infection/positive serology, and (c) no history of SARS-CoV-2 infection/negative serology. We were able to obtain an expanded VST product from donors 1 and 2 (1.6x and 1.8x increase of baseline VST count, respectively) consisting in CD3 + cells (80.3% and 62.7%, respectively) with CD4 + dominance (60% in both donors). Higher numbers of VST were obtained from the donor 2 as compared to donor 1. T-cell clonality test showed oligoclonal reproducible peaks on a polyclonal background for both donors. In contrast, VST could be neither expanded nor primed in a donor without evidence of prior infection. This proof-of-concept study supports the feasibility of expanding ex vivo SARS-CoV-2-specific VST from blood of convalescent donors. The results raise the question of whether the selection of seropositive donors may be a strategy to obtain cell lines enriched in their SARS-CoV-2-specificity for future adoptive transfer to immunosuppressed patients.

Kinetics of Torque Teno virus DNA in stools may predict occurrence of acute intestinal graft versus host disease early after allogeneic hematopoietic stem cell transplantation.

Torque Teno virus (TTV) DNA load in blood may act as a marker of immune competence after allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). Conflicting data have been reported as to the value of this biomarker for anticipating acute Graft versus host disease (aGvHD) occurrence. Here, we hypothesized that quantitation of TTV DNA load in stool specimens early after allo-HSCT could be used to identify patients at high risk of acute intestinal graft versus host disease (aIGvHD). In this prospective two-center study, we recruited a total of 83 nonconsecutive adult patients undergoing allo-HSCT. The study period comprised the first 120 days after allo-HSCT. TTV DNA was quantitated in paired stool samples collected at a median of 2 days prior to cell infusion and at a median of 14 days after allo-HSCT by real-time PCR. Thirty-seven patients developed aGVHD, of whom 25 had aIGVHD (diagnosed at a median of 42 days after allo-HSCT). Median TTV DNA load values in posttransplant stools specimens were comparable (P = .34) in patients with or without subsequent aIGvHD; nevertheless, a falling trajectory (decrease in TTV DNA load >0.5 log10 copies/0.1 g) in paired pretransplant and posttransplant specimens was independently associated with the occurrence of aIGvHD (OR, 5.2; 95% CI, 1.3-21.3; P = .02). Notably, displaying a rising trajectory had a negative predictive value of 87.5% for aIGvHD. In summary, in this hypothesis-generating study, we suggest that the decrease in TTV DNA load from baseline in stool specimens may identify patients at risk of aIGVHD.

Cytomegalovirus DNA load monitoring in stool specimens for anticipating the occurrence of intestinal acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: Is it of any value?

BACKGROUND: Data have been published suggesting a bidirectional interaction between cytomegalovirus (CMV) infection and acute graft-versus-host disease (aGvHD) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Here, we hypothesized that prospective CMV DNA monitoring in stool specimens may be useful for predicting subsequent occurrence of intestinal aGvHD (IaGvHD). METHODS: This two-center study enrolled 121 consecutive adult patients undergoing any modality of allo-HSCT. A total of 1,009 stool specimens were collected (a median of 7 specimens/patient; range, 1-18). CMV DNA monitoring in stools and plasma was performed using real-time PCR assays. RESULTS: CMV DNA was detected in stools in 20 patients (cumulative incidence, 16.9%; 95% CI, 6.3%-31.8%). Median CMV DNA level in stool specimens was 1,258 IU/0.1g (range, 210-4,087 IU/0.1 g). All these patients and their donors were CMV seropositive, and 16 of the 20 patients also had CMV DNAemia, while 4 patients had CMV DNA detected in stools without CMV DNAemia. No correlation was found between CMV DNA loads in plasma and stools (P = .40). Prior CMV DNAemia, aGvHD, or IaGvHD were not associated with presence of CMV DNA in feces. IaGvHD was present in 30 patients, in 5 of whom CMV DNA was detected in stools. Neither detection of CMV DNA in feces nor in plasma was associated with subsequent IaGvHD (OR, 0.67; 95% CI, 0.18-2.52; P = .55 and OR, 0.86; 95% CI, 0.38-1.96; P = .71, respectively). No patient in this cohort had CMV end-organ disease within the study period. CONCLUSION: Our study failed to provide evidence pointing to a reciprocal interaction between GI CMV infection and IaGvHD. CMV DNA monitoring in stools seems of no value to anticipate occurrence of IaGvHD.

Assessment of immunodeficiency scoring index performance in enterovirus/rhinovirus respiratory infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT). OBJECTIVE: We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (>16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers. RESULTS: We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent factors associated with LRTD progression: Ig G < 400 mg/dL, community-acquired respiratory virus (CARV) co-infection and high-risk ISI. Inclusion of Ig G levels and CARV co-infection in the ISI improved its performance by significantly increasing the area under the receiver operator characteristic curve (AUROC) from 0.643 to 0.734 (P = .03). Likewise, the two conditions identified by multivariate analyses as associated with higher probability of mortality were high-risk ISI and EvRh infection within 6 months after transplant. CONCLUSIONS: Our findings confirm the value of high-risk ISI in predicting both probability of EvRh LRTD and 3-month overall mortality. We also demonstrate that the original ISI could be adapted to other CARV types by including additional variables to improve its performance.

Community acquired respiratory virus infections in adult patients undergoing umbilical cord blood transplantation.

Characteristics and risk factors (RFs) of community-acquired respiratory virus (CARV) infections after umbilical cord blood transplantation (UCBT) are lacking. We retrospectively analyzed CARV infections in 216 single-unit myeloablative UCBT recipients. One-hundred and fourteen episodes of CARV infections were diagnosed in 62 (29%) patients. Upper respiratory tract disease (URTD) occurred in 61 (54%) whereas lower respiratory tract disease (LRTD) in 53 (46%). The 5-year cumulative incidence of CARV infection was 29%. RFs for developing CARV infections were: prednisone-based graft-versus-host disease (GVHD) prophylaxis and grade II-IV acute GVHD. RFs analysis of CARV progression to LRTD identified 2007-2009 period and absolute lymphocyte count (ALC) < 0.5 × 109/L. ALC < 0.5 × 109/L had a negative impact on day 60 mortality in both overall CARV and those with LRTD, whereas proven LRTD was associated with higher day 60 mortality. CARV infections had a negative effect on non-relapse mortality. Overall survival at day 60 after CARV detection was significantly lower in recipients with LRTD compared with URTD (74% vs. 93%, respectively). In conclusion, CARV infections after UCBT are frequent and may have a negative effect in the outcomes, in particular in the context of lymphocytopenia.

The clinical benefit of instituting a prospective clinical community-acquired respiratory virus surveillance program in allogeneic hematopoietic stem cell transplantation.

BACKGROUND: There is a lack of studies comparing clinical outcomes among retrospective versus prospective cohorts of allogeneic stem cell transplant (allo-HCT) recipients with community acquired respiratory virus (CARV) infections. METHODS: We compare outcomes in two consecutive cohorts of allo-HCT recipients with CARV infections. The retrospective cohort included 63 allo-HCT recipients with 108 CARV infections from January 2013 to April 2016 who were screened and managed following standard clinical practice based on influenza and respiratory syncytial virus rapid antigen detection methods. The prospective cohort was comprised of 144 consecutive recipients with 297 CARV episodes included in a prospective interventional clinical surveillance program (ProClinCarvSur-P) based on syndromic multiplex PCR as first-line test from May 2016 to December 2018 at a single transplant center. RESULTS: CARV infections in the retrospective cohort showed more severe clinical features at the time of diagnosis compared to the prospective cohort (fever 83% vs. 57%, hospital admission 69% vs. 28% and lower respiratory tract 58% vs. 31%, respectively, p ≤ 0.002 for all comparisons). Antiviral therapy was more commonly prescribed in the prospective cohort (69 vs. 43 treated CARV episodes), particularly at the upper respiratory tract disease stage (34 vs. 12 treated CARV episodes). Three-month all-cause mortality was significantly higher in the retrospective cohort (n = 23, 37% vs. n = 10, 7%, p < 0.0001). Multivariate logistic regression analysis showed that recipients included in ProClinCarvSur-P had lower mortality rate [odds ratio 0.31, 95% confidence interval 0.12-0.7, p = 0.01]. CONCLUSION: This study report on outcome differences when reporting retrospective vs. prospective CARV infections after allo-HCT. Recipients included in a ProClinCarvSur-P had lower mortality.

The effect of timing on community acquired respiratory virus infection mortality during the first year after allogeneic hematopoietic stem cell transplantation: a prospective epidemiological survey.

The effect of timing of community acquired respiratory virus (CARV) infection after allogeneic hematopoietic stem cell transplant (allo-HCT) is an as yet unsettled issue. We evaluate this issue by including all consecutive allo-HCT recipients with molecularly-documented CARV infection during the first year after transplant. The study cohort was drawn from a prospective longitudinal survey of CARV in allo-HCT recipient having respiratory symptoms conducted from December 2013 to December 2018 at two Spanish transplant centers. Respiratory viruses in upper and/or lower respiratory specimens were tested using multiplex PCR panel assays. The study cohort comprised 233 allo-HCT recipients with 376 CARV infection episodes diagnosed during the first year after allo-HCT. Overall, 60% of CARV episodes occurred within the first 6 months (227 out of 376). Thirty patients (13%) had died at 3 months after CARV detection, of which 25 (83%) were recipients developing CARV within the first 6 months after transplant. Multivariate analysis identified four risk factors for mortality: ATG used as part of conditioning regimen [odds ratio (OR) 2.8, 95% confidence interval (C.I.) 1.21-6.4, p = 0.01], CARV lower respiratory tract disease (OR 3.4, 95% C.I. 1.4-8.4, p = 0.007), CARV infection within the first 6 months of transplant (OR 3.04, 95% C.I. 1.1-8.7, p = 0.03), and absolute lymphocyte count <0.2 × 109/L (OR 2.4, 95% C.I. 1-5.3, p = 0.04). Developing CARV infection within the first 6 months was associated with higher mortality. Our data supports that the timing of CARV development after allo-HCT could be of major interest.

Incidence, risk factors, and outcome of pulmonary invasive fungal disease after respiratory virus infection in allogeneic hematopoietic stem cell transplantation recipients.

BACKGROUND: There is growing evidence that community-acquired respiratory virus (CARV) increases the risk of pulmonary invasive fungal disease (IFD) in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) setting. To date, there is a lack of knowledge regarding the risk factors (RFs), as well as the most critical period for subsequent onset of IFD after CARV infections in allo-HSCT recipients. METHODS: In this prospective longitudinal observational CARV survey, we analyzed the effect of CARV on subsequent IFD development in 287 adult allo-HSCT recipients diagnosed with 597 CARV episodes from December 2013 to December 2018. Multiplex PCR panel assays were used to test CARVs in respiratory specimens. FINDINGS: Twenty-nine out of 287 allo-HSCT recipients (10%) developed IFD after a CARV episode. The median time of IFD onset was 21 days (range, 0-158 days) from day of the first CARV detection. Generalized estimating equation model identified 4 risk factors for IFD: ATG-based conditioning regimen [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.05-5.2, P = .038], CARV lower respiratory tract disease (OR 10.6, 95% CI 3.7-30.8, P < .0001), CARV infection during the first year after transplant (OR 5.34, 95% CI 1.3-21.8, P = .014), and corticosteroids during CARV (OR 2.6, 95% CI 1.1-6.3, P = .03). CONCLUSION: Allo-HSCT recipients conditioned with ATG and under corticosteroid therapy at the time of CARV LRTD during the first year after transplant may require close monitoring for subsequent IFD.

Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia.

OBJECTIVES: To date no definitive cut-off value for cytomegalovirus (CMV) DNA load in bronchoalveolar lavage (BAL) fluid specimens has been established to discriminate between CMV pneumonia and pulmonary CMV DNA shedding in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. METHODS: The current retrospective study is aimed at assessing the range of CMV DNA loads quantified in BAL fluid specimens from allo-HSCT patients with pneumonia in which different microorganisms were causally involved. RESULTS: A total of 144 BAL specimens from 123 patients were included. CMV DNA was detected in 56 out of 144 BAL fluid specimens and the median CMV DNA load from patients in whom CMV pneumonia was unlikely or could be tentatively ruled out was 1210 (31-68, 920) IU/ml. The frequency of CMV DNA detection and median CMV DNA loads were comparable, irrespective of the attributable cause of pneumonia. Detection of CMV DNA loads in BAL fluid specimens >500 IU/ml was independently associated with pneumonia-attributable mortality. CONCLUSIONS: The current study highlights the difficulty in establishing universal CMV DNA load thresholds in BAL fluid specimens for distinguishing between CMV pneumonia and pulmonary CMV DNA shedding, and suggests that the presence of CMV DNA in BAL fluid specimens beyond a certain level may have a deleterious impact on patient outcome.

Clinical Effectiveness of Influenza Vaccination After Allogeneic Hematopoietic Stem Cell Transplantation: A Cross-sectional, Prospective, Observational Study.

BACKGROUND: Vaccination is the primary method for preventing influenza respiratory virus infection (RVI). Although the influenza vaccine is able to achieve serological responses in some allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, its clinical benefits are still uncertain. METHODS: In this prospective, cross-sectional study, we retrospectively analyzed the effect of inactivated trivalent influenza vaccination on the prevalence of influenza RVI in a consecutive cohort of 136 allo-HSCT adult recipients who developed 161 RVI over 5 flu seasons (from 2013 to 2018). Respiratory viruses in upper- and/or lower-respiratory tract specimens were tested using multiplex polymerase chain reaction panel assays. RESULTS: Overall, we diagnosed 74 episodes (46%) of influenza RVI in 70 allo-HSCT recipients. Influenza RVI occurred in 51% of the non-vaccinated compared to 36% of the vaccinated recipients (P = .036). A multivariate analysis showed that influenza vaccination was associated with a lower prevalence of influenza RVI (odds ratio [OR] 0.39, P = .01). A multivariate risk factor analysis of lower-respiratory tract disease (LRTD) identified 2 conditions associated with the probability of influenza RVI progression: influenza vaccination (OR 0.12, 95% confidence interval [CI] 0.014-1, P = .05) and a high-risk immunodeficiency score (OR 36, 95% CI 2.26-575, P = .011). Influenza vaccination was also associated with a lower likelihood of an influenza-related hospital admission (14% vs 2%, P = .04). CONCLUSIONS: This study shows that influenza vaccination may have a clinical benefit in allo-HSCT recipients with virologically-confirmed RVI, in terms of a lower influenza RVI prevalence, slower LRTD progression, and lower likelihood of hospital admission.

Community-acquired respiratory virus lower respiratory tract disease in allogeneic stem cell transplantation recipient: Risk factors and mortality from pulmonary virus-bacterial mixed infections.

Risk factors (RFs) and mortality data of community-acquired respiratory virus (CARVs) lower respiratory tract disease (LRTD) with concurrent pulmonary co-infections in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is scarce. From January 2011 to December 2017, we retrospectively compared the outcome of allo-HSCT recipients diagnosed of CARVs LRTD mono-infection (n = 52, group 1), to those with viral, bacterial, or fungal pulmonary CARVs LRTD co-infections (n = 15, group 2; n = 20, group 3, and n = 11, group 4, respectively), and with those having bacterial pneumonia mono-infection (n = 19, group 5). Overall survival (OS) at day 60 after bronchoalveolar lavage (BAL) was significantly higher in group 1, 2, and 4 compared to group 3 (77%, 67%, and 73% vs 35%, respectively, P = .012). Recipients of group 5 showed a trend to better OS compared to those of group 3 (62% vs 35%, P = .1). Multivariate analyses showed bacterial co-infection as a RF for mortality (hazard ratio[HR] 2.65, 95% C.I. 1.2-6.9, P = .017). We identified other 3 RFs for mortality: lymphocyte count <0.5 × 109 /L (HR 2.6, 95% 1.1-6.2, P = .026), the occurrence of and CMV DNAemia requiring antiviral therapy (CMV-DNAemia-RAT) at the time of BAL (HR 2.32, 95% C.I. 1.1-4.9, P = .03), and the need of oxygen support (HR 8.3, 95% C.I. 2.9-35.3, P = .004). CARV LRTD co-infections are frequent and may have a negative effect in the outcome, in particular in the context of bacterial co-infections.

Role of 3-dimensional power Doppler sonography in differentiating pregnant women with threatened preterm labor from those with an asymptomatic short cervix.

OBJECTIVES: To compare cervical volumes and vascularization indices using 3-dimensional power Doppler sonography among singleton pregnancies with threatened preterm labor and an asymptomatic short cervix. METHODS: Three hundred asymptomatic healthy pregnant women between 24 and 34.6 gestational weeks were prospectively scanned for cervical length. If cervical length was short, defined as below the 10th percentile for gestational age, the cervical volume and vascularization indices (vascularization index [VI], vascularization-flow index [VFI], and flow index [FI]) were measured. Women receiving any treatment for preterm delivery prevention were excluded. During this period, the same sonographic parameters were measured among patients with threatened preterm labor admitted to our institution during the first 24 hours after admission. Multiple pregnancies and fetal or maternal pathologic conditions, were exclusion criteria. Data on body mass index, maternal age, smoking, parity, family history of preterm birth, mother who was born preterm, and previous preterm birth among the pregnant women were recorded. Sonographic and medical history parameters were compared between the two groups. RESULTS: Twenty-nine asymptomatic healthy women (9.6%) had a short cervix. Additionally, 71 pregnancies with threatened preterm labor were scanned. There were no statistically significant differences between the groups in medical history parameters or cervical length. The cervical volume was smaller in threatened preterm cases (12.90 versus 17.168 cm(3); P = .005). The VI and VFI were lower in women with an asymptomatic short cervix (VI, 4.369% versus 15.939%; P < .001; VFI, 1.514 versus 4.878; P < .001). The FI was higher in the short cervix group (33.581 versus 30.311; P = .006). CONCLUSIONS: Three-dimensional transvaginal sonography reveals differences in cervical volume and vascularization indices between pregnancies with an asymptomatic short cervix and cases with threatened preterm labor, although cervical length is similar in both groups.

Genetic characterization of the Spanish Trotter horse breed using microsatellite markers

To assist in selection schemes we carried out the first genetic characterization of the Spanish Trotter horse (Trotador Español). We used 16 microsatellite markers to genotype 40 unrelated Spanish trotters, 25 native Balearic horses (11 Menorquina and 14 Mallorquina horses) and 32 Andalusian horses. The observed heterozygosity for the Spanish Trotters was 0.647 ± 0.037 and the expected heterozygosity was 0.696 ± 0.026 while the average number of alleles per locus was 6.0 ± 0.341, these values being similar to the data published for other horse breeds. We also tried to establish the importance of the Mallorquina and Menorquina breeds in the present Spanish Trotter population. Only 9 percent of the total genetic variability could be attributed to differences between breeds (mean F ST = 0.09 ± 0.010). Recent migration rates were confirmed the low recent genetic relationship between the Balearic breeds and Spanish Trotters, indicating that the genetic background of the present Spanish Trotter population is not based on the native Balearic horse population.