Outcomes After Vascular Surgery Procedures in Patients with COVID-19 Infection: A National Multicenter Cohort Study (COVID-VAS).

OBJECTIVES: To analyze the outcome of vascular procedures performed in patients with COVID-19 infection during the 2020 pandemic. METHODS: This is a multicenter, prospective observational cohort study. We analyzed data from 75 patients with COVID-19 infection undergoing vascular surgery procedures in 17 hospitals across Spain and Andorra between March and May 2020. The primary end point was 30-day mortality. Clinical Trials registry number NCT04333693. RESULTS: The mean age was 70.9 (45-94) and 58 (77.0%) patients were male. Around 70.7% had postoperative complications, 36.0% of patients experienced respiratory failure, 22.7% acute renal failure, and 22.7% acute respiratory distress syndrome (ARDS). All-cause 30-days mortality rate was 37.3%. Multivariate analysis identified age >65 years (P = 0.009), American Society of Anesthesiologists (ASA) classification IV (P = 0.004), preoperative lymphocyte count <0.6 (×109/L) (P = 0.001) and lactate dehydrogenase (LDH) >500 (UI/L) (P = 0.004), need for invasive ventilation (P = 0.043), postoperative acute renal failure (P = 0.001), ARDS (P = 0.003) and major amputation (P = 0.009) as independent variables associated with mortality. Preoperative coma (P = 0.001), quick Sepsis Related Organ Failure Assessment (qSOFA) score ≥2 (P = 0.043), lymphocytes <0.6 (×109/L) (P = 0.019) leucocytes >11.5 (×109/L) (P = 0.007) and serum ferritin >1800 mg/dL (P = 0.004), bilateral lung infiltrates on thorax computed tomography (P = 0.025), and postoperative acute renal failure (P = 0.009) increased the risk of postoperative ARDS. qSOFA score ≥2 was the only risk factor associated with postoperative sepsis (P = 0.041). CONCLUSIONS: Patients with COVID-19 infection undergoing vascular surgery procedures showed poor 30-days survival. Age >65 years, preoperative lymphocytes <0.6 (x109/L) and LDH >500 (UI/L), and postoperative acute renal failure, ARDS and need for major amputation were identified as prognostic factors of 30-days mortality.

Factors associated with the orthopaedic surgeon's decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1905 patients.

OBJECTIVE: To determine factors associated with orthopaedic surgeons' decision to recommend total joint replacement (TJR) in people with knee and hip osteoarthritis (OA). DESIGN: Cross-sectional study in eleven countries. For consecutive outpatients with definite hip or knee OA consulting an orthopaedic surgeon, the surgeon's indication of TJR was collected, as well as patients' characteristics including comorbidities and social situation, OA symptom duration, pain, stiffness and function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), joint-specific quality of life, Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) radiographic grade (0-4), and surgeons' characteristics. Univariable and multivariable logistic regressions were performed to identify factors associated with the indication of TJR, adjusted by country. RESULTS: In total, 1905 patients were included: mean age was 66.5 (standard deviation [SD], 10.8) years, 1082 (58.0%) were women, mean OA symptom duration was 5.0 (SD 7.0) years. TJR was recommended in 561/1127 (49.8%) knee OA and 542/778 (69.7%) hip OA patients. In multivariable analysis on 516 patients with complete data, the variables associated with TJR indication were radiographic grade (Odds Ratio, OR for one grade increase, for knee and hip OA, respectively: 2.90, 95% confidence interval [1.69-4.97] and 3.30 [2.17-5.03]) and WOMAC total score (OR for 10 points increase: 1.65 [1.32-2.06] and 1.38 [1.15-1.66], respectively). After excluding radiographic grade from the analyses, on 1265 patients, greater WOMAC total score was the main predictor for knee and hip OA; older age was also significant for knee OA. CONCLUSION: Radiographic severity and patient-reported pain and function play a major role in surgeons' recommendation for TJR.

The global burden attributable to low bone mineral density.

INTRODUCTION: The Global Burden of Disease Study 2010 estimated the worldwide health burden of 291 diseases and injuries and 67 risk factors by calculating disability-adjusted life years (DALYs). Osteoporosis was not considered as a disease, and bone mineral density (BMD) was analysed as a risk factor for fractures, which formed part of the health burden due to falls. OBJECTIVES: To calculate (1) the global distribution of BMD, (2) its population attributable fraction (PAF) for fractures and subsequently for falls, and (3) the number of DALYs due to BMD. METHODS: A systematic review was performed seeking population-based studies in which BMD was measured by dual-energy X-ray absorptiometry at the femoral neck in people aged 50 years and over. Age- and sex-specific mean ± SD BMD values (g/cm(2)) were extracted from eligible studies. Comparative risk assessment methodology was used to calculate PAFs of BMD for fractures. The theoretical minimum risk exposure distribution was estimated as the age- and sex-specific 90th centile from the Third National Health and Nutrition Examination Survey (NHANES III). Relative risks of fractures were obtained from a previous meta-analysis. Hospital data were used to calculate the fraction of the health burden of falls that was due to fractures. RESULTS: Global deaths and DALYs attributable to low BMD increased from 103 000 and 3 125 000 in 1990 to 188 000 and 5 216 000 in 2010, respectively. The percentage of low BMD in the total global burden almost doubled from 1990 (0.12%) to 2010 (0.21%). Around one-third of falls-related deaths were attributable to low BMD. CONCLUSIONS: Low BMD is responsible for a growing global health burden, only partially representative of the real burden of osteoporosis.

Spanish consensus document for acceptance and rejection of kidneys from expanded criteria donors.

In the recent years, more than 60% of available deceased donors are either older than 50 yr or have significant vascular comorbidities. This makes the acceptance and rejection criteria of renal allografts very rigorous, especially in cases of younger recipients, and at the same time encourages live donations. In our country, there is a lack of homogeneity in the percentages of use of expanded criteria donor (ECD) allografts between the different autonomous communities. Furthermore, the criteria vary greatly, and in some cases, great importance is given to the biopsy while in others very little. In this study, we present a unified and homogenous criteria agreed upon by consensus of a 10-member Panel representing major scientific societies related to renal transplantation in Spain. The criteria are to be used in accepting and/or rejecting kidneys from the so-called ECDs. The goal was to standardize the use of these organs, to optimize the results, and most importantly to provide for the maximum well being of our patients. Finally, we believe that after taking into account the Panel's thorough review of specific scientific literature, this document will be adaptable to other national renal transplant programmes.

[Serial voiding urosonography: a safe technique for the study of the entire urinary tract in children]. / Urosonografía miccional seriada: una técnica segura para el estudio de toda la vía urinaria en pediatría.

For more than a decade, serial voiding urosonography has been one of the imaging modalities used to detect vesicoureteral reflux in children and it is now also used to study the urethra. The main advantage of this technique is it does not irradiate. Given the important recognition of serial voiding urosonography by the European Society of Pediatric Radiology at the last congress in May 2011, we think it is useful to describe how to carry out this technique successfully. In this update on serial voiding urosonography, we describe the indications, the entire procedure, and the different characteristics of this technique, which we understand will soon become the technique of choice for screening for vesicoureteral reflux as well as for urethral pathology in children.

Functional results in children with retinopathy of prematurity treated with intravitreal bevacizumab.

BACKGROUND/AIM: The aim of the study is to describe the efficacy and to determine the functional outcome in terms of visual acuity and refractive defect of a single dose of intravitreal bevacizumab in patients with high-risk ROP type 1. METHODS: In this retrospective clinical study patients diagnosed between December 2013 and January 2018 with high-risk pre-threshold ROP type 1 and treated with intravitreal bevacizumab were selected. All patients were treated following the established protocol at our centre. Those patients with less than three-year follow-up were excluded. Visual acuity and cycloplegic refraction in the last visit were registered. Treatment efficacy was defined as the absence of retreatment with intravitreal anti-VEGF or laser during follow-up. RESULTS: A total of 38 infants (76 eyes) were included in the analysis. Twenty infants (40 eyes) completed visual acuity testing. Mean age was 6 years (IQR: 4-9). Median visual acuity was 0.8 (IQR: 0.5-1). Thirty-four eyes (85%) had good visual acuity (greater than or equal to 0.5). Thirty-seven patients (74 eyes) had cycloplegic refraction measured. Median spherical equivalent at the last visit was +0.94 (IQR: -0.25; 1.88). Treatment success rate was 96.05%. CONCLUSION: Intravitreal bevacizumab treatment showed good functional outcome in patients with high-risk ROP type 1. In our study, good response to treatment was observed with a success rate over 95%.

Long-term results of biopsy-guided selection and allocation of kidneys from older donors in older recipients.

In our old-for-old program, we discard or allocate older extended criteria donor kidneys to single (SKT) or dual kidney transplantation (DKT) depending on histological Remuzzi's score in recipients older than 60 years. Here, we analyze the long-term results of this program and try to identify independent predictors of patient and graft survival. Between December 1996 and January 2008, we performed 115 SKT and 88 DKT. Discard rate was 15%. Acute rejection incidence was higher in SKT than in DKT (22.6% vs. 11.4%, p = 0.04). Renal function was better in DKT than in SKT up to 5 years after transplantation. Surgical complications were frequent in DKT. Ten-year cumulative graft survival was significantly lower in the SKT group (31% vs. 53%, p = 0.03). In SKT, histological score 4 provided similar graft survival than 3 or less, whereas in DKT score 4, 5 or 6 displayed similar outcome. Finally, independent predictors of graft survival were history of major adverse cardiac event and 1-year serum creatinine, rather than SKT or DKT. In conclusion, this biopsy-guided old-for-old strategy resulted in acceptable long-term graft survival. Our results suggest that DKT should be considered for scores of 5 or 6 only.

The role of pain and functional impairment in the decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1909 patients. Report of the OARSI-OMERACT Task Force on total joint replacement.

OBJECTIVE: To assess the pain and functional disability levels corresponding to an indication for total joint replacement (TJR) in hip and knee osteoarthritis (OA). DESIGN: International cross-sectional study in 10 countries. PATIENTS: Consecutive outpatients with definite hip or knee OA attending an orthopaedic outpatient clinic. Gold standard measure for recommendation for TJR: Surgeon's decision that TJR is justified. OUTCOME MEASURES: Pain (ICOAP: intermittent and constant osteoarthritis pain, 0-100) and functional impairment (HOOS-PS/KOOS-PS: Hip/Knee injury and Osteoarthritis Outcome Score Physical function Short-form, 0-100). ANALYSES: Comparison of patients with vs without surgeons' indication for TJR. Receiver Operating Characteristic (ROC) curve analyses and logistic regression were applied to determine cut points of pain and disability defining recommendation for TJR. RESULTS: In all, 1909 patients were included (1130 knee/779 hip OA). Mean age was 66.4 [standard deviation (SD) 10.9] years, 58.1% were women; 628/1130 (55.6%) knee OA and 574/779 (73.7%) hip OA patients were recommended for TJR. Although patients recommended for TJR (yes vs no) had worse symptom levels [pain, 55.5 (95% confidence interval 54.2, 56.8) vs. 44.9 (43.2, 46.6), and functional impairment, 59.8 (58.7, 60.9) vs. 50.9 (49.3, 52.4), respectively, both P<0.0001], there was substantial overlap in symptom levels between groups, even when adjusting for radiographic joint status. Thus, it was not possible to determine cut points for pain and function defining 'requirement for TJR'. CONCLUSION: Although symptom levels were higher in patients recommended for TJR, pain and functional disability alone did not discriminate between those who were and were not considered to need TJR by the orthopaedic surgeon.

Acute oral, pulmonary and intravenous toxicity/pathogenicity testing of a new formulation of Bacillus thuringiensis var israelensis SH-14 in rats.

During the last decades, efforts are being made to develop microbial insecticides as biological control agents. Bacillus thuringiensis has been one of the most consistent and significant biopesticides for using on crops as an insecticidal spray. The aim of this study was to assess and to compare the pathogenicity of a new formulation of B.thuringiensis var israelensis SH-14 in rats through oral, intranasal and intravenous single dosing. Through 21 days after administration, clinical examinations were performed daily, and body weight gain was evaluated. Clearance was estimated by means of collection of feces or examination of lungs and blood, and infectivity was evaluated enumerating microorganisms from organs of Bti SH-14 treated animals sacrificed at intervals. Gross necropsy of animals was performed at interim or final sacrifice. There were no treatment-related mortalities, and no evidence of pathogenicity or treatment related toxicity, although in the intravenous study, the microorganism was capable of achieving persistence in organs after administration, and the Bti SH-14 treated animals developed skin ulcerations and hemorrhages at the injection site. It could be concluded that the tested microorganism was not toxic or pathogenic to rats via oral or intranasal route, although it was capable of achieving persistence in organs after intravenous administration, eliciting local effects at the injection site.

Prematurity and ADHD in Childhood: An Observational Register-Based Study in Catalonia.

Objective: To evaluate the association between prematurity (by the gestational week [gw]) and ADHD during childhood. Method: Observational, matched cohort study using data from children born in a tertiary-level hospital (Hospital Universitari Vall d'Hebron, Catalonia, Spain) during 1995-2007 and data from the Information System for the Development of Research in Primary Health Care (SIDIAP database, Catalonia, Spain). Results: Prevalence of ADHD increases as gestational age decreases, 12.7% for those born ≤28 gw, compared to 3.2% for those born after the 37 gw. The risk of developing ADHD in the non-premature children tends to increase as the gw decreases (35-36 gw, hazard ratio [HR] = 1.70, 95% confidence interval [CI] [1.19, 2.44]; 33-34 gw, HR = 3.38, 95% CI [2.08, 5.50]; 29-32 gw, HR = 2.37, 95% CI [1.54, 3.63]; and ≤28 gw, HR = 5.57, 95% CI [2.49, 12.46]) Conclusion: Being born preterm is associated with a risk of developing ADHD, also in late preterm children (35-36 gw). Attention when taking care of these infants regarding their mental health must be made.

PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate.

Fructose-2,6-bisphosphate is responsible for mediating glucagon-stimulated gluconeogenesis in the liver. This discovery has led to the realization that this compound plays a significant role in directing carbohydrate fluxes in all eukaryotes. Biophysical studies of the enzyme that both synthesizes and degrades this biofactor have yielded insight into its molecular enzymology. Moreover, the metabolic role of fructose-2,6-bisphosphate has great potential in the treatment of diabetes.

Our experience in the management of prostate cancer in renal transplant recipients. / Nuestra experiencia en el manejo del cáncer de próstata en pacientes trasplantados renales.

INTRODUCTION AND OBJECTIVES: The management of Prostate cancer (PCa) in renal transplant recipients (RTR) is challenging and remain controversial. Currently there is no consensus about this condition. The aim of the study was to analyse our experience in the diagnosis and management of PCa in RTR. METHOD: Retrospective monocentric study of a prospective and consecutive database from 2003-2017. Inclusion of RTR diagnosed of PCa. Staging and treatment in agreement with the contemporary guidelines. The main outcome measures included clinical staging, type of treatment, oncological outcomes and follow-up. RESULTS: 1,330 renal transplants were performed (787 males), diagnosed of PCa in 33 RTR (4.2%), mean age 66years±6.3 (51-78). Median PSA was 8.8ng/ml and PSA ratio 0.19. Mean time between renal transplantation and PCa diagnosis 130months±90 (2-236). TREATMENTS: Radical prostatectomy (RP) (n=22; 66.7%), Radiation therapy (RT) with Androgen deprivation therapy (ADT) (n=7; 21.2%), Active surveillance (n=3; 9.1%), ADT (n=1; 3%). No graft loss neither impaired renal function due to PCa treatment was reported. After RP two patients (9.1%) presented biochemical recurrence treated with RT. Remission of the 100%. Mean follow-up was 61months±37 (6-132). CONCLUSIONS: PCa in renal transplant patients can be managed with the same therapeutic options as in the general population. Active surveillance should also be provided in RTR despite being under immunosuppressive therapy.

Simultaneous bilateral percutaneous nephrolithotomy: Effectiveness and safety. / Nefrolitotomía percutánea bilateral simultánea: Eficacia y seguridad".

OBJECTIVES: To evaluate the effectiveness and safety of simultaneous bilateral percutaneous nephrolithotomy performed in patients affected with bilateral renal calculi. MATERIALS AND METHODS: This is a prospective study from September 2012 to November 2016. Patients diagnosed of bilateral kidney stones with abdominal CT scan were included. Surgical technique prone position, renal puncture guided by fluoroscopy and tract dilation up to 24Ch. We reviewed demographic and stone characteristics, stone free rate, clinical success, complications and follow-up. RESULTS: During the study period, 732 percutaneous nephrolithotomies were performed. Eighteen patients were included (36 renal units, 2.5%), 13 men and 5 women, with a median age of 58 years and an interquartile range (IQR) of 40-66. Median stone burden was 228mm2 (IQR 134-389); median operative time, 150minutes (IQR 97-180); and median hospital stay, 5 days (IQR 5-15). Stone free rate was 80%. Residual calculi were encountered in 8 renal units (22.2%) and required other complementary techniques for their complete tesolution 4 external shockwave lithotripsies, one open ureterolithotomy, 2 ureteroscopies and one second look. Major complications included 4 cases of severe hemorrhage managed with angiographic embolization. The median follow-up was 36 months (range 26-46). CONCLUSIONS: Simultaneous bilateral percutaneous nephrolithotomy is an effective and safe procedure in patients affected with bilateral renal calculi. It is a surgical challenge that should be performed in selected patients and in centers with experience.

The Latin American experience of allografting patients with severe aplastic anaemia: real-world data on the impact of stem cell source and ATG administration in HLA-identical sibling transplants.

We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P=0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P=0.18), and for grades III-IV was 2.6% vs 11.6% (P=0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P=0.002) and extensive 5% vs 23.6% (P=0.01). OS was 74% vs 76% for BM vs PBSCs (P=0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P=0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P=0.005) respectively. In multivariate analysis, aGvHD II-IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1-5.6, P=0.02) and aGvHD III-IV (HR 8.3 CI 3.4-20.2, P<0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patients.

The human ubiquitous 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene (PFKFB3): promoter characterization and genomic structure.

A DNA fragment containing 1.5 kb of the 5'-flanking region of the human ubiquitous PFKFB3 gene, coding for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, was cloned and its promoter activity was examined. The 5' flanking region contains a TATA box-like and GC-rich sequences, yielding several potential Specific protein (Sp-1) and activator protein (AP)-2 binding sites. Putative regulatory motifs for E-box, nuclear factor (NF)-1 and progesterone response element were also found by computer assisted analysis. Transient expression assays of truncated promoter-reporter constructs in HeLa cells showed that this gene is induced by phorbol esters (PDB) and cyclic-AMP-dependent protein kinase signal activation. Furthermore, the genomic organization of the PFKFB3 gene is reported. This gene spans more than 26 kb containing at least 16 exons that accounts for the two reported isoforms, inducible and ubiquitous, generated through alternative splicing of exon 15.

The antiproliferative activity of the murine interferon-inducible Ifi 200 proteins depends on the presence of two 200 amino acid domains.

Interferon-inducible proteins, p200, have a modular organization consisting of one (p203) or two (p202 and p204) 200 amino acid motifs, designated as type a or b domains. The relationship between this domain organization and the antiproliferative activity was investigated by generating a hybrid protein with the 204 a domain upstream from the 203 b domain. This 204a/203b protein inhibits the proliferation of transfected cells, delays G0/G1 progression into S phase following serum restimulation, and inhibits the E2F-mediated transcriptional activity. These results demonstrate for the first time that both a and b domains are needed for inhibition of proliferation by the Ifi 200 proteins.

In vitro and in vivo expression analysis of the interferon-inducible 203 gene.

The interferon (IFN)-inducible protein family 200 is encoded by structurally related genes located on mouse chromosome 1. The encoded proteins so far characterized and designated p202, p204, and pD3 contain at least one copy of a conserved 200 amino acid domain in addition to other regions that are different or missing among the various family members. We have recently characterized a cDNA clone (203 cDNA) encoding a 408 amino acid protein bearing structural similarities to p202 and p204. Here, we report its pattern of expression in vitro and in vivo. In vitro, the mRNA and protein encoded by the 203 gene were increased by IFN-alpha in several cell lines of different histologic origin. By contrast, no significant induction was observed in vivo in mice from C57BL/6 and BALB/c strains even after treatment with the IFN-inducer poly rI:rC. In addition, the constitutive expression of 203 gene was restricted to some myeloid and lymphoid tissues, namely, thymus, bone marrow, and spleen. Comparison of the expression pattern of the 203 and 202 genes in three mouse strains revealed that they exhibit a differential inducibility by IFN and a reciprocal expression pattern. The 203 mRNA was constitutively expressed in C57BL/6 and BALB/c mice and undetectable in the spleen of DBA/2 mice. The 202 mRNA was strongly induced by poly rI:rC in the spleen of DBA/2 and BALB/c mice but absent in C57BL/6 mice. Southern analysis revealed a restriction fragment length polymorphism in the 203 locus. Taken as a whole, these results demonstrate a remarkable difference in the in vivo IFN responsiveness of two members belonging to the same gene family with a similar degree of IFN inducibility in vitro. Moreover, the reciprocal expression pattern in C57BL/6 and DBA/2 mice could mean that p203 and p202 play the same role in a mouse strain in which only one of them is expressed.

A good alternative to reduce the kidney shortage: kidneys from nonheartbeating donors.

BACKGROUND: Because of the shortage of kidneys available for transplantation, we began in 1985 to harvest kidneys from non-heartbeating (NHB) donors. METHODS: We compared the results of a group of 66 kidney recipients from NHB donors (NHB group) with 122 kidney recipients from heartbeating donors (HB group). We analyzed, in the NHB group, the influence of ischemia times in graft survival and we tested the best cut-offs by receiver operating characteristic curves. We also studied, using a univariate and multivariate Cox hazard model, the capacity of different variables to predict graft loss. RESULTS: Patient and graft survival were similar in both groups during the follow-up. The percentage of delayed graft function was the only significant difference between both groups (NHB group 62% vs. HB group 32%; P=0.0001). Delayed graft function, in the NHB group, is influenced by the warm ischemia time, which is directly related to the number of days to achieve a serum creatinine<300 mmol/L (P=0.0001). The best cut-off times in this group were 45 min for warm ischemia time and 22 hr for cold ischemia time. Recipients have a greater likelihood of losing the graft beyond those limits (P=0.017, relative risk: 7.3). The incidence of acute rejection was similar in both groups, and it was the only predictor factor of graft loss in the complete series of patients (P=0.0001), in the NHB group (P=0.007), and in the HB group (P=0.02). CONCLUSIONS: Reducing the incidence of acute rejection and shortening ischemia time are conditions needed to guarantee a long graft survival of kidneys from NHB donors.

The anticytomegaloviral activity of raltitrexed is abrogated in quiescent mouse fibroblasts that overexpress thymidylate synthase.

Cytomegalovirus (CMV) replication in non-proliferating cells requires the coordinated expression of the host enzymes responsible for deoxyribonucleotide synthesis. Thymidylate synthase (TS) is an essential cellular enzyme that catalyzes de novo synthesis of thymidylic acid (dTMP). In this report we show that murine CMV (MCMV) replication and DNA synthesis are inhibited in quiescent 3T6 fibroblasts by raltitrexed, a quinazoline-based folate analog that specifically inhibits TS. This antiviral activity was abrogated in LU3-7 cells, a 3T6 derivative that overproduces TS by about 50-fold. These observations indicate that the anticytomegaloviral activity of raltitrexed is associated with TS inhibition and suggest that cellular TS activity is required for efficient CMV replication in quiescent cells.