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Estudio descriptivo retrospectivo de enero de 1995 – febrero de 2011 de pacientes intervenidos de cirugía de preservación de válvula aórtica. Material y métodos: Se han intervenido un total de 30 pacientes, con anuloectasia o aneurisma de senos de Valsalva, 18 según la técnica de David y 12 pacientes con técnica de Yacoub. La media de edad fue de 50 años (intervalo entre 22–77 años). De los pacientes del estudio 80% fueron hombres y 20% mujeres. La mortalidad hospitalaria fue de 2 pacientes (6,6%), 1 paciente en postoperatorio por accidente cerebrovascular (ACV) hemorrágico y otro que hubo de ser reintervenido por insuficiencia aórtica aguda; 1 paciente se reintervino en postoperatorio inmediato por sangrado sin ninguna otra complicación posterior a destacar. En el ecocardiograma previo al alta los pacientes presentaron correcto funcionamiento de la válvula, y en el seguimiento a largo plazo, 3 pacientes (10,7%) se reintervinieron y se les implantó una prótesis mecánica (2 previa intervención de David y 1 paciente previa intervención de Yacoub). No hubo complicaciones hemorrágicas ni tromboembólicas durante el seguimiento. Conclusión: En nuestra experiencia, la preservación de la válvula aórtica con reimplante valvular o remodelación de la raíz aórtica ha mostrado unos resultados excelentes. Evita las complicaciones tromboembólicas y hemorrágicas derivadas de las prótesis y de la anticoagulación crónica, proporcionando unos resultados hemodinámicos y una calidad de vida excelentes.

Objective: To evaluate the effect of a daily nutritionist consultation on rectal volume, gas, and prostate displacement during Stereotactic Body Radiation Treatment (SBRT) with an endorectal spacer., Methods: Twenty-six consecutive patients receiving 5 fraction SBRT with endorectal spacing were prospectively enrolled for an intensive daily nutritionist intervention utilizing biofeedback based on image guidance from each fraction. A retrospective control cohort receiving a standard bowel preparation was compared. Rectal volume, rectal gas, and prostate displacement were assessed by analysis of cone beam computed tomography. Data was analyzed using the SPSS statistics software., Results: Intense dietary intervention with biofeedback led to a consistently lower rectal gas score over 5 fractions (P<0.001) and less variability in rectal volume during prostate SBRT indicating a nonsignificant trend for superior preparation in the intervention group compared with controls, particularly for the first 2 fractions. However, there was no significant impact on prostate displacement as measured by couch correction., Conclusions: Intense dietary consultations effectively reduce rectal gas and variation of rectal volume during prostate SBRT with endorectal spacing. However, there was no advantage in reducing prostate displacement. Thus, labor-intensive daily nutritionist intervention with biofeedback is not cost-effective in reducing organ motion in patients with endorectal spacers compared with standard pretreatment dietary advice and is not recommended., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. In this retrospective international case-control study, we evaluated 41 listeriosis episodes occurring between 2000 and 2021 in HCT recipients (111 transplant centers in 30 countries) and assessed risk factors for listeriosis by comparisons with matched controls. The 41 listeriosis episodes (all due to Listeria monocytogenes [LM]) occurred in 30 allogeneic (allo)-HCT recipients and 11 autologous (auto)-HCT recipients at a median of 6.2 months (interquartile range [IQR], 1.6 to 19.3 months) post-HCT. The estimated incidence was 49.8/100,000 allo-HCT recipients and 13.7/100,000 auto-HCT recipients. The most common manifestations in our cohort were fever (n = 39; 95%), headache (n = 9; 22%), diarrhea, and impaired consciousness (n = 8 each; 20%). Four patients (10%) presented with septic shock, and 19 of 38 (50%) were severely lymphocytopenic. Thirty-seven patients (90%) had LM bacteremia. Eleven patients (27%) had neurolisteriosis, of whom 4 presented with nonspecific signs and 5 had normal brain imaging findings. Cerebrospinal fluid analysis revealed high protein and pleocytosis (mainly neutrophilic). Three-month mortality was 17% overall (n = 7), including 27% (n = 3 of 11) in patients with neurolisteriosis and 13% (n = 4 of 30) in those without neurolisteriosis. In the multivariate analysis comparing cases with 74 controls, non-first HCT (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.10 to 30.82; P = .038); and lymphocytopenia <500 cells/mm 3 (OR, 7.54; 95% CI, 1.50 to 37.83; P = .014) were significantly associated with listeriosis. There were no statistically significant differences in background characteristics, immunosuppression, and cotrimoxazole prophylaxis between cases and controls. HCT recipients are at increased risk for listeriosis compared to the general population. Listeriosis cause severe disease with septic shock and mortality. Neurolisteriosis can present with nonspecific signs and normal imaging. Lymphocytopenia and non-first HCT are associated with an increased risk of listeriosis, and cotrimoxazole was not protective., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Helicobacter cinaedi is known to cause invasive infections in immunocompromised adults. Here we report the first case of H. cinaedi bacteremia in a child with nephrotic syndrome. The patient presented with a mild transient febrile illness that resolved spontaneously. We discuss the diagnostic challenges associated with this case and the microbiologic approach, including genomic analysis. Furthermore, we review the current case together with all previous pediatric cases (n = 6). Notably, all cases involved neonates or otherwise immunocompromised individuals and were characterized by severe disease with complicated infections (eg, meningitis, cholangitis and arthritis). H. cinaedi bacteremia in children is associated with a wide spectrum of clinical presentations ranging from mild to life-threatening conditions. This bacterium may be difficult to diagnose and require specialized methods., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration., Methods: This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (<96 h of treatment start) composed the modified intent-to-treat (mITT) population. Primary efficacy endpoint was treatment success at the end of study treatment (EOST) as determined by the Data Review Committee. Success was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at the EOST., Results: Treatment success was 80% (16/20, mITT; EOST) and Day 30 survival was 85% (17/20; 3 deaths unrelated to fosmanogepix). Ten of 21 (48%) were switched to oral fosmanogepix. Fosmanogepix was well tolerated with no treatment-related serious adverse events/discontinuations. Fosmanogepix had potent in vitro activity against baseline isolates of Candida spp. (MICrange: CLSI, 0.002-0.03 mg/L)., Conclusions: Results from this single-arm Phase 2 trial suggest that fosmanogepix may be a safe, well-tolerated, and efficacious treatment for non-neutropenic patients with candidaemia, including those with renal impairment., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objective: Ophthalmological pathologies such as glaucoma, diabetic retinopathy and age-related macular degeneration are major causes of blindness and vision impairment. There is a need for novel decision support tools that can simplify and speed up the diagnosis of these pathologies. A key step in this process is to automatically estimate the quality of the fundus images to make sure these are interpretable by a human operator or a machine learning model. We present a novel fundus image quality scale and deep learning (DL) model that can estimate fundus image quality relative to this new scale., Methods: A total of 1245 images were graded for quality by two ophthalmologists within the range 1-10, with a resolution of 0.5. A DL regression model was trained for fundus image quality assessment. The architecture used was Inception-V3. The model was developed using a total of 89,947 images from 6 databases, of which 1245 were labeled by the specialists and the remaining 88,702 images were used for pre-training and semi-supervised learning. The final DL model was evaluated on an internal test set (n=209) as well as an external test set (n=194)., Results: The final DL model, denoted FundusQ-Net, achieved a mean absolute error of 0.61 (0.54-0.68) on the internal test set. When evaluated as a binary classification model on the public DRIMDB database as an external test set the model obtained an accuracy of 99%., Significance: the proposed algorithm provides a new robust tool for automated quality grading of fundus images., Competing Interests: Declaration of Competing Interest Prof. Ingeborg Stalmans holds equities in MONA a spin off from the Catholic University of Leuven and the Belgian research institute VITO. MONA develops a solution to diagnose eye diseases from retinal pictures with artificial intelligence. The other authors have no conflicts of interests to declare., (Copyright © 2023. Published by Elsevier B.V.)

In order to characterize pneumococcal endovascular infection in the post-vaccination era, a retrospective nationwide study based on the Israeli Adult IPD database was conducted. Between 2010 and 2019, 0.6% (23 cases) of IPD cases were of endovascular type, occurring mainly in males (72.3%) with underlying medical conditions (78.2%). Additional pneumococcal source (10 patients) and concomitant infections were not uncommon. Penicillin and ceftriaxone susceptibility rates were 65.2% and 91.3%, respectively; 60.9% of the isolates were not covered by the pneumococcal conjugate vaccine. 21.7% of patients died during hospitalization. In conclusion, pneumococcal endovascular infections still carry significant morbidity and mortality., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A significant amount of the carbon (C) assimilated in photosynthesis by trees is re-emitted to the atmosphere via the respiratory CO2 flux of roots. Because of technical constraints, we have little understanding of the extent and dynamics of the respiratory CO2 flux of roots at the total root system scale (RCF). This study aimed to fill this gap and to quantify the daily C budget of entire trees. We used aeroponics as a novel approach to measure directly and simultaneously RCF and the net CO2 flux of the entire shoot (SCF), to estimate their night- and day-time contributions to daily tree CO2 budget and to estimate the relative contribution of different root categories to RCF in large saplings of the tropical tree species Ceiba pentandra (L.) Gaertn. By maintaining root temperature within a narrow range (24-27.5 °C), we controlled for its effect on RCF, thus allowing the potential relationship between RCF and SCF to be tested. The carbon gain of the fast-growing saplings was 0.79 ± 0.10 g C sapling-1 day-1, with day-time shoot CO2 uptake outweighing night-time shoot and day- and night-time root CO2 losses by a factor of two. Other than a slight rise in the morning hours, RCF was relatively stable and not coupled to the daily dynamics of SCF. Albeit having lower specific respiration rates compared with fine-roots, the relative contributions of coarse-roots (diameter >2 mm) to RCF were substantial because of their large biomass and were estimated to range from 43 to 63% of RCF at midday of different days during the growing season. The results of this study suggest that (i) the entire root system needs to be monitored for its impact on the tree CO2 budget, (ii) RCF cannot be derived from SCF and (iii) the importance of coarse-root respiration to RCF may be greater than appreciated., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Immune reconstitution inflammatory syndrome (IRIS) is increasingly reported in various HIV negative patients with immunosuppression, but the relationship with hematopoietic cell transplantation (HCT) is not well defined. We report a case of IRIS in a patient infected with pulmonary and CNS Nocardiosis following HCT due to primary myelofibrosis., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Advances in treatment for multiple myeloma (MM) patients entail a high risk for opportunistic infections such as invasive pulmonary aspergillosis (IPA)., Objectives: This study was conducted to describe the patient's profile, clinical manifestations, diagnosis and outcome of MM patients with IPA, in our large haemato-oncology centre., Patients/methods: We retrospectively analysed patients with MM who underwent Broncho alveolar lavage for pneumonia at Rambam Hospital during a 13-year period from July 2005 to February 2018. We focused on those with Aspergillus pneumonia., Results: Of the 669 patients with multiple myeloma, mean age 62.6 (±7.6) years, forty-two patients (6.2%) were diagnosed with IPA. Among them, 60% had a probable diagnosis and 40% possible. Clinical presentation was similar for IPA and other pulmonary infections. Compared to those with other pulmonary infections, IPA was more commonly diagnosed in patients with long-standing disease (p = .00012) and among patients receiving 3 or more lines of myeloma therapies (p = .04). Thirty-day mortality rates following diagnostic bronchoscopy did not differ between IPA and non-IPA patients. (p = .85)., Conclusions: Multiple myeloma patients had an increased risk for IPA, most notably in patients with 3 or more lines of anti-myeloma treatment and more advanced disease. This clearly emphasises the vigilance needed for IPA in these patients., (© 2021 Wiley-VCH GmbH.)

The early detection of blood in urine (hematuria) can play a crucial role in the treatment of serious diseases ( e . g ., infections, kidney disease, schistosomiasis, and cancer). Therefore, the development of low-cost portable biosensors for blood detection in urine has become necessary. Here, we designed an ultrasensitive whole-cell bacterial biosensor interfaced with an optoelectronic measurement module for heme detection in urine. Heme is a red blood cells (RBCs) component that is liberated from lysed cells. The bacterial biosensor includes Escherichia coli cells carrying a heme-sensitive synthetic promoter integrated with a luciferase reporter ( luxCDABE ) from Photorhabdus luminescens . To improve the bacterial biosensor performance, we re-engineered the genetic structure of luxCDABE operon by splitting it into two parts ( luxCDE and luxAB ). The luxCDE genes were regulated by the heme-sensitive promoter, and the luxAB genes were regulated by either constitutive or inducible promoters. We examined the genetic circuit's performance in synthetic urine diluent supplied with heme and in human urine supplied with lysed blood. Finally, we interfaced the bacterial biosensor with a light detection setup based on a commercial optical measurement single-photon avalanche photodiode (SPAD). The whole-cell biosensor was tested in human urine with lysed blood, demonstrating a low-cost, portable, and easy-to-use hematuria detection with an ON-to-OFF ratio of 6.5-fold for blood levels from 5 × 10 4 to 5 × 10 5 RBC per mL of human urine.

One of the key knowledge gaps in the field of Alzheimer's disease research is the lack of understanding of how amyloid beta and tau cooperate to cause neurodegeneration. We recently generated a mouse model (APP/PS1 + Tau) that develops amyloid plaque pathology and expresses human tau in the absence of endogenous murine tau. These mice exhibit an age-related behavioural hyperactivity phenotype and transcriptional deficits which are ameliorated by tau transgene suppression. We hypothesized that these mice would also display memory and hippocampal synaptic plasticity deficits as has been reported for many plaque bearing mouse models which express endogenous mouse tau. We observed that our APP/PS1 + Tau model does not exhibit novel object memory or robust long-term potentiation deficits with age, whereas the parent APP/PS1 line with mouse tau did develop the expected deficits. These data are important as they highlight potential functional differences between mouse and human tau and the need to use multiple models to fully understand Alzheimer's disease pathogenesis and develop effective therapeutic strategies., (© 2020 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Patients with hematological malignancies and allogeneic hematopoietic stem-cell transplant recipients carry a high risk of rare (non-Aspergillus molds and non-Candida yeasts) invasive fungal infections (IFI)., Methods: We retrospectively evaluated and described the patient profile, clinical manifestations, isolated species, treatment and outcome of patients with hematological malignancies diagnosed with these rare IFIs during 15 years in a large single hemato-oncology center., Results: Eighty-seven patients with hematological malignancies treated in our center had at least one positive culture or molecular identification of a rare fungus. Ninety-three isolates were considered the etiological agents of the infection. The most common underlying hematological malignancy was acute myeloid leukemia, 36 patients (41.4%). Eighty patients (91%) received chemotherapy less than 30 days prior to IFI diagnosis. The most frequent site of infection was the respiratory tract: 34 patients (39%) had pulmonary and 19 patients (22%) had a sinusal or nasopharyngeal infections. Disseminated infection, defined as positive blood cultures or parallel infection in multiple organ systems, was documented in 20 patients (23%). The most common fungal species were Fusarium (35%) and Zygomycetes (25%). Coinfection with more than one fungus was noted in 20 patients (23%). Forty-seven of 87 patients (54%) in this study died within 90 days of IFI diagnosis., Conclusions: Rare IFIs in patients with hematological malignancy become increasingly frequent. Early identification with traditional and molecular methods is important in management of these patients.

Despite the important role of tropical forest ecosystems in the uptake and storage of atmospheric carbon dioxide (CO2), the carbon (C) dynamics of tropical tree species remains poorly understood, especially regarding belowground roots. This study assessed the allocation of newly assimilated C in the fast-growing pioneer tropical tree species Ceiba pentandra (L.), with a special focus on different root categories. During a 5-day pulse-labelling experiment, 9-month-old (~3.5-m-tall) saplings were labelled with 13CO2 in a large-scale aeroponic facility, which allowed tracing the label in bulk biomass and in non-structural carbohydrates (sugars and starch) as well as respiratory CO2 from the canopy to the root system, including both woody and non-woody roots. A combined logistic and exponential model was used to evaluate 13C mean transfer time and mean residence time (MRT) to the root systems. We found 13C in the root phloem as early as 2 h after the labelling, indicating a mean C transfer velocity of 2.4 ± 0.1 m h-1. Five days after pulse labelling, 27% of the tracers taken up by the trees were found in the leaves and 13% were recovered in the woody tissue of the trunk, 6% in the bark and 2% in the root systems, while 52% were lost, most likely by respiration and exudation. Larger amounts of 13C were found in root sugars than in starch, the former also demonstrating shorter MRT than starch. Of all investigated root categories, non-woody white roots (NRW) showed the largest 13C enrichment and peaked in the deepest NRW (2-3.5 m) as early as 24 ± 2 h after labelling. In contrast to coarse woody brown roots, the sink strength of NRW increased with root depth. The findings of this study improve the understanding of C allocation in young tropical trees and provide unique insights into the changing contributions of woody and non-woody roots to C sink strengths with depth., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Carbon (C) dynamics in canopy and roots influence whole-tree carbon fluxes, but little is known about canopy regulation of tree-root activity. Here, the patterns and dynamics of canopy-root C coupling are assessed in tropical trees. Large aeroponics facility was used to study the root systems of Ceiba pentandra and Khaya anthotheca saplings directly at different light intensities. In Ceiba, root respiration (R r ) co-varied with photosynthesis (A n ) in large saplings (3-to-7-m canopy-root axis) at high-light, but showed no consistent pattern at low-light. At medium-light and in small saplings (c. 1-m axis), R r tended to decrease transiently towards midday. Proximal roots had higher R r and nonstructural carbohydrate concentrations than distal roots, but canopy-root coupling was unaffected by root location. In medium-sized Khaya, no R r pattern was observed, and in both species, R r was unrelated to temperature. The early-afternoon increase in R r suggests that canopy-root coupling is based on mass flow of newly fixed C in the phloem, whereas the early-morning rise in R r with A n indicates an additional coupling signal that travels faster than the phloem sap. In large saplings and potentially also in higher trees, light and possibly additional environmental factors control the diurnal patterns of canopy-root coupling, irrespective of root location., (© 2019 The Authors. New Phytologist © 2019 New Phytologist Trust.)

A key knowledge gap blocking development of effective therapeutics for Alzheimer's disease (AD) is the lack of understanding of how amyloid beta (Aβ) peptide and pathological forms of the tau protein cooperate in causing disease phenotypes. Within a mouse tau-deficient background, we probed the molecular, cellular, and behavioral disruption triggered by the influence of wild-type human tau on human Aβ-induced pathology. We find that Aβ and tau work cooperatively to cause a hyperactivity behavioral phenotype and to cause downregulation of transcription of genes involved in synaptic function. In both our mouse model and human postmortem tissue, we observe accumulation of pathological tau in synapses, supporting the potential importance of synaptic tau. Importantly, tau reduction in the mice initiated after behavioral deficits emerge corrects behavioral deficits, reduces synaptic tau levels, and substantially reverses transcriptional perturbations, suggesting that lowering synaptic tau levels may be beneficial in AD., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Invasive pulmonary aspergillosis (IPA) has dire consequences in hemato-oncological patients. We report our experience with performing routine baseline chest computed tomography for early diagnosis of IPA. We found high rates of proven or probable IPA diagnosed on admission among patients with newly diagnosed acute myeloid leukemia., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: This study aimed to evaluate the diagnostic role of PCR detection of Aspergillus DNA in the broncho-alveolar lavage (BAL) fluid in a large cohort of patients suspected to have invasive pulmonary aspergillosis (IPA)., Methods: Consecutive immunocompromised patients who underwent bronchoscopy with BAL sampling and PCR detection of Aspergillus DNA for the diagnosis of pulmonary infiltrates were included in the study. Galactomannan (GM) antigen testing in BAL and serum and BAL fungal culture were also performed. Patients were classified as having IPA (proven/probable/possible) or no-IPA according to the EORTC/MSG diagnostic criteria., Results: During 12 years (2005-2016), 1248 bronchoscopies were performed for 1072 patients. 77% had hematological malignancy, of them 40% had AML and 35.6% underwent HSCT. IPA was diagnosed in 531 patients (42.5%), 7-proven, 280-probable and 244-possible. PCR was positive in 266 cases, of them 213 had IPA, indicating a true positive rate of 80% (213/266) and a false positive rate of 20% (53/266). These results establish the diagnostic performance of PCR to have sensitivity of 40%, specificity of 93%, PPV- 80% and NPV-68%. Of 244 patients with possible IPA, 80 had positive PCR. Including PCR in the diagnostic criteria would move 80 cases from the possible group to the probable one. A combination of positive PCR and/or BAL-GM increases sensitivity to 74%, while positivity of both tests elevates PPV to 99.4%., Conclusions: Inclusion PCR for the detection of Aspergillus-DNA in BAL in the mycological criteria of the EORTC/MSG definitions increases the rate and the certainty of IPA diagnosis., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited and CRE infections remain associated with high clinical failure and mortality rates, particularly in vulnerable patient populations. A Phase 3, multinational, open-label, randomized controlled trial (TANGO II) was conducted from 2014 to 2017 to evaluate the efficacy/safety of meropenem-vaborbactam monotherapy versus best available therapy (BAT) for CRE., Methods: A total of 77 patients with confirmed/suspected CRE infection (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, complicated urinary tract infection/acute pyelonephritis) were randomized, and 47 with confirmed CRE infection formed the primary analysis population (microbiologic-CRE-modified intent-to-treat, mCRE-MITT). Eligible patients were randomized 2:1 to meropenem-vaborbactam (2 g/2 g over 3 h, q8h for 7-14 days) or BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, tigecycline; or ceftazidime-avibactam alone). Efficacy endpoints included clinical cure, Day-28 all-cause mortality, microbiologic cure, and overall success (clinical cure + microbiologic eradication). Safety endpoints included adverse events (AEs) and laboratory findings., Results: Within the mCRE-MITT population, cure rates were 65.6% (21/32) and 33.3% (5/15) [95% confidence interval (CI) of difference, 3.3% to 61.3%; P = 0.03)] at End of Treatment and 59.4% (19/32) and 26.7% (4/15) (95% CI of difference, 4.6% to 60.8%; P = 0.02) at Test of Cure;.Day-28 all-cause mortality was 15.6% (5/32) and 33.3% (5/15) (95% CI of difference, - 44.7% to 9.3%) for meropenem-vaborbactam versus BAT, respectively. Treatment-related AEs and renal-related AEs were 24.0% (12/50) and 4.0% (2/50) for meropenem-vaborbactam versus 44.0% (11/25) and 24.0% (6/25) for BAT. Exploratory risk-benefit analyses of composite clinical failure or nephrotoxicity favored meropenem-vaborbactam versus BAT (31.3% [10/32] versus 80.0% [12/15]; 95% CI of difference, - 74.6% to - 22.9%; P < 0.001)., Conclusions: Monotherapy with meropenem-vaborbactam for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT., Clinical Trials Registration: NCT02168946., Funding: The Medicines Company.

Objectives: The risk of cytomegalovirus (CMV) reactivation in multiple myeloma (MM) patients treated with bortezomib-based induction regimens is increased following autologous stem cell transplantation (ASCT). There is paucity of data regarding the risk of CMV infections in MM patients who did not receive bortezomib and ASCT., Methods: We herein report three cases of heavily pretreated MM patients, receiving daratumumab-containing combination regimens, in whom ASCT had been performed long ago and who recently developed severe CMV-related gastrointestinal disease., Results: All the three patients had a prolonged CMV disease course requiring a long-term antiviral treatment. All the patients suffered from CMV colitis. One patient had concurrent CMV duodenitis and another patient had a concurrent CMV retinitis., Conclusion: Novel myeloma treatments prolong patient survival and more patients with profound immunosuppression following multiple lines of therapies are seen in clinical practice. These patients may present with opportunistic infections that were rare in the past. Our findings suggest a possible association between daratumumab therapy (in combination with other immunosuppressive therapies) and severe CMV gastrointestinal disease. A longer follow-up is needed to explore long-term side effects of novel agents like daratumumab in newly diagnosed as well as heavily pretreated MM patients., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)