The complementary value of intraoperative fluorescence imaging and Raman spectroscopy for cancer surgery: combining the incompatibles.

A clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown particular benefit in improving complete resection of tumour tissue. However, signal processing for fluorescence imaging is complex, and fluorescence signal intensity does not always perfectly correlate with tumour location. Raman spectroscopy has the capacity to accurately differentiate between malignant and healthy tissue based on their molecular composition. In Raman spectroscopy, specificity is uniquely high, but signal intensity is weak and Raman measurements are mainly performed in a point-wise manner on microscopic tissue volumes, making whole-field assessment temporally unfeasible. In this review, we describe the state-of-the-art of both optical techniques, paying special attention to the combined intraoperative application of fluorescence imaging and Raman spectroscopy in current clinical research. We demonstrate how these techniques are complementary and address the technical challenges that have traditionally led them to be considered mutually exclusive for clinical implementation. Finally, we present a novel strategy that exploits the optimal characteristics of both modalities to facilitate resection with clear surgical margins.

Caffeine and Paraxanthine as Tracers of Anthropogenic Wastewater in Coastal Lagoons in Yucatan, Mexico.

Due to karstic bedrock geology and poor wastewater management practices, anthropogenic activities are impacting water quality in Yucatan's aquatic systems. Specifically, raw wastewater inputs to the aquifer subsequently flow to coastal lagoons through groundwater fluxes. This study establishes the presence of anthropogenic wastewater by measuring caffeine and its metabolite, paraxanthine, in four of Yucatan's major coastal lagoons: Celestun, Chelem, Dzilam de Bravo, and Ria Lagartos. Concentrations of caffeine ranged from non-detected (ND) to 2390 ng L-1 and paraxanthine from ND to 212 ng L-1, which correspond with pollution threats from anthropogenic wastewater inputs. The potential sources are: (1) direct in situ discharges from nearby urban settlements; and (2) contribution from submerged groundwater discharges. Overall, results indicate the potential of caffeine as an environmental tracer of anthropogenic wastewater contamination for the region.

mTOR mutations in Smith-Kingsmore syndrome: Four additional patients and a review.

Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features. Germline or mosaic mutations of the mTOR gene have been detected in all patients. The mTOR gene is a key regulator of cell growth, cell proliferation, protein synthesis and synaptic plasticity, and the mTOR pathway (PI3K-AKT-mTOR) is highly regulated and critical for cell survival and apoptosis. Mutations in different genes in this pathway result in known rare diseases implicated in hemi/megalencephaly with epilepsy, as the tuberous sclerosis complex caused by mutations in TSC1 and TSC2, or the PIK3CA-related overgrowth spectrum (PROS). We here present 4 new cases of SKS, review all clinical and molecular aspects of this disorder, as well as some characteristics of the patients with only brain mTOR somatic mutations.

Environmental Exposure of Children to Toxic Trace Elements (Hg, Cr, As) in an Urban Area of Yucatan, Mexico: Water, Blood, and Urine Levels.

Merida is the largest urban center in the Mexican State of Yucatan. Here domestic sewage is deposited in poorly built septic tanks and is not adequately treated. Because of contamination from such waste, water from the top 20 m of the aquifer is unsuitable for human consumption. Given this situation and because children are highly vulnerable to environmental pollution, including exposure to toxic trace elements, this study focused on evaluating the exposure of children to arsenic (As), chromium (Cr), and mercury (Hg) in water. It also evaluated the relationship between the levels of these elements in water and their concentrations in urine and blood. Among the 33 children monitored in the study, arsenic surpassed WHO limits for blood in 37% of the cases, which could result from the ingestion of poultry contaminated with organoarsenic compounds. In the case of WHO limits for Mercury, 65% of the water samples analyzed, 28% of urine samples, and 12% of blood samples exceeded them. Mercury exposure was correlated with biological sex, some lifestyle factors, and the zone in Merida in which children live. These data suggest that the levels of some toxic metals in children may be affected by water source, socioeconomic factors, and individual behavior.

Water Consumption as Source of Arsenic, Chromium, and Mercury in Children Living in Rural Yucatan, Mexico: Blood and Urine Levels.

Studies investigating the correlation between metal content in water and metal levels in children are scarce worldwide, but especially in developing nations. Therefore, this study investigates the correlation between arsenic, chromium, and mercury concentrations in drinking and cooking water and in blood and urine samples collected from healthy and supposedly non-exposed children from a rural area in Yucatan, Mexico. Mercury in water shows concentrations above the recommended World Health Organization (WHO) value for drinking and cooking water. Also, 25% of the children show mercury in urine above the WHO recommended value. Multivariate analyses show a significant role for drinking and cooking water as a vector of exposure in children. Also, the factor analysis shows chronic exposure in the case of arsenic, as well as an ongoing detoxification process through urine in the case of mercury. Further studies should be done in order to determine other potential metal exposure pathways among children.

Discrimination between oral cancer and healthy tissue based on water content determined by Raman spectroscopy.

Tumor-positive resection margins are a major problem in oral cancer surgery. High-wavenumber Raman spectroscopy is a reliable technique to determine the water content of tissues, which may contribute to differentiate between tumor and healthy tissue. The aim of this study was to examine the use of Raman spectroscopy to differentiate tumor from surrounding healthy tissue in oral squamous cell carcinoma. From 14 patients undergoing tongue resection for squamous cell carcinoma, the water content was determined at 170 locations on freshly excised tongue specimens using the Raman bands of the OH-stretching vibrations (3350-3550 cm(-1)) and of the CH-stretching vibrations (2910-2965 cm(-1)). The results were correlated with histopathological assessment of hematoxylin and eosin stained thin tissue sections obtained from the Raman measurement locations. The water content values from squamous cell carcinoma measurements were significantly higher than from surrounding healthy tissue (p-value < 0.0001). Tumor tissue could be detected with a sensitivity of 99% and a specificity of 92% using a cutoff water content value of 69%. Because the Raman measurements are fast and can be carried out on freshly excised tissue without any tissue preparation, this finding signifies an important step toward the development of an intraoperative tool for tumor resection guidance with the aim of enabling oncological radical surgery and improvement of patient outcome.

Surgical management of patients with colorectal cancer and simultaneous liver and lung metastases.

BACKGROUND: The management of patients with colorectal cancer and simultaneously diagnosed liver and lung metastases (SLLM) remains controversial. METHODS: The LiverMetSurvey registry was interrogated for patients treated between 2000 and 2012 to assess outcomes after resection of SLLM, and the factors associated with survival. SLLM was defined as liver and lung metastases diagnosed 3 months or less apart. Survival was compared between patients with resected isolated liver metastases (group 1, control), those with resected liver and lung metastases (group 2), and patients with resected liver metastases and unresected (or unresectable) lung metastases (group 3). An Akaike test was used to select variables for assessment of survival adjusted for confounding variables. RESULTS: Group 1 (isolated liver metastases, hepatic resection alone) included 9185 patients, group 2 (resection of liver and lung metastases) 149 patients, and group 3 (resection of liver metastases, no resection of lung metastases) 285 patients. Ten variables differed significantly between groups and seven were included in the model for adjusted survival (age, number of liver metastases, synchronicity of liver metastases with primary tumour, carcinoembryonic antigen level, node status of the primary tumour, initial resectability of liver metastases and inclusion in group 3). Adjusted overall 5-year survival was similar for groups 1 and 2 (51·5 and 44·5 per cent respectively), but worse for group 3 (14·3 per cent) (P = 0·001). CONCLUSION: Patients who had resection of liver and lung metastases had similar overall survival to those who had undergone removal of isolated liver metastases.

Impacts of geochemical and environmental factors on seasonal variation of heavy metals in a coastal lagoon Yucatan, Mexico.

This study investigated the influence of geochemical and environmental factors on seasonal variation in metals in Yucatan's Chelem lagoon. Anthropogenic activities discharge non-treated wastewater directly into it with detrimental environmental consequences. Accordingly, this study established the spatial and temporal patterns of fine grain sediments and concentrations of heavy metals. Multivariate analyses showed fine grain facies deposition, transition sites dominated by fine grain transport, and fine grain erosion sites. Spatial and temporal variations of heavy metals concentration were significant for Cd, Cu, Cr, and Pb. As, Cd, and Sn were as much as 12 times higher than SQuiRTs standards (Buchman 2008). The results indicate that aquifer water is bringing metals from relatively far inland and releasing them into the lagoon. Thus, it appears that the contamination of this lagoon is highly complex and must take into account systemic connections with inland anthropogenic activates and pollution, as well as local factors.

Lactobacillus plantarum IFPL935 impacts colonic metabolism in a simulator of the human gut microbiota during feeding with red wine polyphenols.

The colonic microbiota plays an important role in the bioavailibility of dietary polyphenols. This work has evaluated the impact on the gut microbiota of long-term feeding with both a red wine polyphenolic extract and the flavan-3-ol metabolizer strain Lactobacillus plantarum IFPL935. The study was conducted in the dynamic Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The feeding of the gut microbiota model with red wine polyphenols caused an initial decrease in the counts of total bacteria in the ascending colon (AC), with Bacteroides, Clostridium coccoides/Eubacterium rectale and Bifidobacterium being the most affected bacterial groups. The bacterial counts recovered to initial numbers faster than the overall microbial fermentation and proteolysis, which seemed to be longer affected by polyphenols. Addition of L. plantarum IFPL935 helped to promptly recover total counts, Lactobacillus and Enterobacteriaceae and led to an increase in lactic acid formation in the AC vessel at the start of the polyphenol treatment as well as butyric acid in the transverse (TC) and descending (DC) vessels after 5 days. Moreover, L. plantarum IFPL935 favoured the conversion in the DC vessel of monomeric flavan-3-ols and their intermediate metabolites into phenylpropionic acids and in particular 3-(3'-hydroxyphenyl)propionic acid. The results open the possibilities of using L. plantarum IFPL935 as a food ingredient for helping individuals showing a low polyphenol-fermenting metabotype to increase their colonic microbial capacities of metabolizing dietary polyphenols.

Patient navigator's role in latent tuberculosis infection at a New York City Health Department Chest Clinic.

Background: Philippines is one of the top ten countries of birth among individuals with tuberculosis in New York City (NYC). The NYC Health Department (HD) screened Filipino-born New Yorkers for latent TB infection (LTBI), but few of those tested positive completed evaluation and treatment. Objective: To increase the proportion of Filipinos with a positive QuantiFeron-TB Gold Plus (QFT-Plus) complete LTBI evaluation and treatment. Methods: Nine community-based LTBI screening events were conducted during September-December 2021. Patients with positive QFT-Plus results were offered no-cost LTBI evaluation and treatment at HD Chest Clinic. The HD engaged culturally- and linguistically-competent Filipino patient navigators (PN) to facilitate LTBI evaluation and treatment. Results: Of 77 Filipinos screened, 17 (22%) tested positive. Fourteen (82%) were evaluated for LTBI; eight of the 14 (57%) completed LTBI treatment. Conclusions: Pairing patients with culturally- and linguistically- competent Filipino PNs contributed to an increase in the proportion of Filipinos with a positive QFT-Plus who completed LTBI evaluation and treatment. TB prevention programs may wish to consider PNs in LTBI patient care.

An oral cancer screening program in Brazil: Analysis of seven years of outcome after its implementation in the suburban cities of São Paulo.

OBJECTIVE: To describe the implementation of an oral cancer screening program at the Barretos Cancer Hospital (BCH) and present the outcome based on data obtained from 2014 to 2020. MATERIALS AND METHODS: The residents of the Regional Health District of Barretos (DRS-V) were personally invited by community health agents or nurses, and among 13,973 people, 15,222 oral examinations were carried out over the years in 18 of its municipalities. Oral examinations were performed at the Mobile Dental Unit and at the Prevention Department of the BCH. Inclusion criteria were being 35 years of age or older, having a personal history of tobacco or alcohol consumption, or having a lesion in the oral cavity found by community health agent or self-reported, regardless of age or risk factors. RESULTS AND CONCLUSION: The main result of our study was the stages of oral cancer among screen detected cases were smaller compared to cases in the hospital registry, in the state and in Brazil. Oral cancer detection rate per 1,000 oral examinations was 10.7.The early stages of oral cancer found by screening in primary care facilities or using mobile units suggest that, when organized, screening may improve the prognosis of oral cancer.

Oleate prevents saturated-fatty-acid-induced ER stress, inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism.

AIMS/HYPOTHESIS: Although the substitution of saturated fatty acids with oleate has been recommended in the management of type 2 diabetes mellitus, the mechanisms by which oleate improves insulin resistance in skeletal muscle cells are not completely known. Here, we examined whether oleate, through activation of AMP-activated protein kinase (AMPK), prevented palmitate-induced endoplasmic reticulum (ER) stress, which is involved in the link between lipid-induced inflammation and insulin resistance. METHODS: Studies were conducted in mouse C2C12 myotubes and in the human myogenic cell line LHCN-M2. To analyse the involvement of AMPK, activators and inhibitors of this kinase and overexpression of a dominant negative AMPK construct (K45R) were used. RESULTS: Palmitate increased the levels of ER stress markers, whereas oleate did not. In palmitate-exposed cells incubated with a lower concentration of oleate, the effects of palmitate were prevented. The induction of ER stress markers by palmitate was prevented by the presence of the AMPK activators AICAR and A-769662. Moreover, the ability of oleate to prevent palmitate-induced ER stress and inflammation (nuclear factor-kappa B [NF-κB] DNA-binding activity and expression and secretion of IL6) as well as insulin-stimulated Akt phosphorylation and 2-deoxyglucose uptake was reversed in the presence of the AMPK inhibitor compound C or by overexpression of a dominant negative AMPK construct. Finally, palmitate reduced phospho-AMPK levels, whereas this was not observed in oleate-exposed cells or in palmitate-exposed cells supplemented with oleate. CONCLUSIONS/INTERPRETATION: Overall, these findings indicate that oleate prevents ER stress, inflammation and insulin resistance in palmitate-exposed skeletal muscle cells by activating AMPK.

Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca.

BACKGROUND: Variant transthyretin amyloidosis (A-ATTRv) is an autosomal dominant disease caused by a range of TTR gene variants which entail great phenotypical heterogeneity and penetrance. In Majorca, the A-ATTRv caused by the V30M gene variant (A-ATTRV30M) is the most common. Since asymptomatic carriers are at risk of developing the disease, estimating age of onset is vital for proper management and follow-up. Thus, the aim of this study was to estimate age-related penetrance in ATTRV30M variant carriers from Majorca. METHODS: The disease risk among carriers from ATTRV30M families from Majorca was estimated by Non-parametric survival estimation. Factors potentially involved in the disease expression, namely gender and parent of origin were also analysed. RESULTS: A total of 48 heterozygous ATTRV30M families (147 affected patients and 123 were asymptomatic carriers) were included in the analysis. Penetrance progressively increased from 6% at 30 years to 75% at 90 years of age. In contrast to other European populations, we observe a similar risk for both males and females, and no difference of risk according to the parent of origin. CONCLUSIONS: In this first study assessing the age-related penetrance of ATTRV30M variant in Majorcan families, no effect of gender or parent of origin was observed. These findings will be helpful for improving management and follow-up of TTR variant carrier individuals.

The peroxisome proliferator-activated receptor (PPAR) ß/δ agonist GW501516 inhibits IL-6-induced signal transducer and activator of transcription 3 (STAT3) activation and insulin resistance in human liver cells.

AIM/HYPOTHESIS: IL-6 induces insulin resistance by activating signal transducer and activator of transcription 3 (STAT3) and upregulating the transcription of its target gene SOCS3. Here we examined whether the peroxisome proliferator-activated receptor (PPAR)ß/δ agonist GW501516 prevented activation of the IL-6-STAT3-suppressor of cytokine signalling 3 (SOCS3) pathway and insulin resistance in human hepatic HepG2 cells. METHODS: Studies were conducted with human HepG2 cells and livers from mice null for Pparß/δ (also known as Ppard) and wild-type mice. RESULTS: GW501516 prevented IL-6-dependent reduction in insulin-stimulated v-akt murine thymoma viral oncogene homologue 1 (AKT) phosphorylation and in IRS-1 and IRS-2 protein levels. In addition, treatment with this drug abolished IL-6-induced STAT3 phosphorylation of Tyr7°5 and Ser7²7 and prevented the increase in SOCS3 caused by this cytokine. Moreover, GW501516 prevented IL-6-dependent induction of extracellular-related kinase 1/2 (ERK1/2), a serine-threonine protein kinase involved in serine STAT3 phosphorylation; the livers of Pparß/δ-null mice showed increased Tyr7°5- and Ser7²7-STAT3 as well as phospho-ERK1/2 levels. Furthermore, drug treatment prevented the IL-6-dependent reduction in phosphorylated AMP-activated protein kinase (AMPK), a kinase reported to inhibit STAT3 phosphorylation on Tyr7°5. In agreement with the recovery in phospho-AMPK levels observed following GW501516 treatment, this drug increased the AMP/ATP ratio and decreased the ATP/ADP ratio. CONCLUSIONS/INTERPRETATION: Overall, our findings show that the PPARß/δ activator GW501516 prevents IL-6-induced STAT3 activation by inhibiting ERK1/2 phosphorylation and preventing the reduction in phospho-AMPK levels. These effects of GW501516 may contribute to the prevention of cytokine-induced insulin resistance in hepatic cells.

Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial.

A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)- to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6-144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized (2:1) to abrupt conversion (<24 h) from CNI to SRL (n = 393) or CNI continuation for up to 6 years (n = 214). Between-group changes in baseline-adjusted mean Cockcroft-Gault GFR at month 12 (primary efficacy end point) were not significant. The primary safety end point, noninferiority of cumulative rate of graft loss or death at 12 months, was not met (6.6% vs. 5.6% in the SRL and CNI groups, respectively). Rates of death at 12 months were not significantly different, and no true graft losses (e.g. liver transplantation) were observed during the 12-month period. At 52 weeks, SRL conversion was associated with higher rates of biopsy-confirmed acute rejection (p = 0.02) and discontinuations (p < 0.001), primarily for adverse events. Adverse events were consistent with known safety profiles. In conclusion, liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI- to SRL-based immunosuppression.

A novel mutation in the ZNF462 gene c.3306dup; p.(Gln1103Thrfs*10) is associated to Weiss-Kruszka syndrome. A case report.

BACKGROUND: Weiss-Kruszka syndrome (WSKA) is a rare disorder caused by mutations in the ZNF462 gene or deletion of 9p31.2 chromosome region, involving ZNF462. The prevalence of WSKA is unknown as only 24 affected individuals have been described. This syndrome should be suspected in individuals presenting mild global developmental delay and common craniofacial abnormalities. CASE PRESENTATION: We presented a case of an infant, 3 years and 4-month life who presented pondostatural and psychomotor retardation, generalized hypotonia with hypermobility, bilateral palpebral ptosis, epicanthal folds, and poorly expressive facies as the main clinical features. These characteristics lead to the realization of genetics studies that resulted in the identification of a novel mutation c.3306dup; p.(Gln1103Thrfs*10) in ZNF462. CONCLUSIONS: WSKA should be suspected in individuals presenting mild global developmental delay, ptosis, downslanting palpebral fissures, exaggerated Cupid's Bow, arched eyebrows, epicanthal folds and short upturned nose with a bulbous tip. Hypertrophy of the ventricular septum and severe OSA were described in our patient and should be considered in future reviews of the disease. This case is added to the reduced number of publications previously reported regarding WSKA and contributes to understanding the genetic characteristics, clinical features, and diagnosis of this syndrome.Abbreviations: WSKA: Weiss-Kruszka syndrome; CP: craniofacial perimeter; WES: whole-exome sequencing; RSV: respiratory syncytial virus; OSA: obstructive sleep apnoea; ACMG: American College of Medical Genetics and Genomics.

Experimental study on needle insertion force to minimize tissue deformation in tongue tissue.

This study reports on the effects of insertion velocity, needle tip geometry and needle diameter on tissue deformation and maximum insertion force. Moreover, the effect of multiple insertions with the same needle on the maximum insertion force is reported. The tissue deformation and maximum insertion force strongly depend on the insertion velocity and the tip geometry. No correlation was found between the outer diameter and the maximum insertion force for small needles (30G - 32G). The endurance experiments showed no remarkable difference in the maximum insertion force during 100 insertions.

Microbiota and gut-brain axis dysfunction in autism spectrum disorder: Evidence for functional gastrointestinal disorders.

INTRODUCTION: The high frequency of functional gastrointestinal disorders (FGIDs) in autism spectrum disorders (ASD) has drawn attention to the composition of gut microbiota as a possible factor in ASD pathogenesis. However, characterization of a distinctive ASD microbial pattern is still unclear. OBJECTIVE: To conduct a narrative review on ASD microbial profile and diversity changes relative to NT children and FGID comorbidity and ASD pathogenesis. METHODOLOGY: First, we searched the PubMed database in peer-reviewed journals for evidence regarding the current epidemiological evidence on FGID comorbidity. For the identification of a microbial profile in ASD children, only original studies examining gut bacterial and fungal abundances and diversity in ASD children and adolescents were included. Lastly, research on the role of microbial dysbiosis as an interface between genetic and environmental risk factors in the pathogenesis of neuropsychiatric disorders, and specifically ASD, was examined. RESULTS: Prevalence and risk of FGIDs is significantly higher in ASD children and correlates with the severity of ASD. Bacterial and fungal diversity differ between ASD and NT children, indicating a difference in taxonomic abundance profiles, which have been reported at all bacterial phylogenetic levels. However, studies analyzing gut microbiota have a heterogeneous methodology and several limitations that could account for the variety of findings for each taxon. Also, covariate analysis reveals influence of demographics, diet, disease severity, GI comorbidity and allergies. Integration of these findings with changes in metabolome and genetic risk factors allowed for a better understanding of microbiota involvement in ASD pathogenesis for future research.

The Fanconi anemia family of genes and its correlation with breast cancer susceptibility and breast cancer features.

Fanconi anemia (FA) family of proteins participates in the DNA repair pathway by homologous recombination, and it is currently formed by 13 genes. Some of these proteins also confer susceptibility to hereditary breast and ovarian cancer (HBOC), since FANCD1 is the BRCA2 breast cancer susceptibility gene, and FANCN/PALB2 and FANCJ/BRIP1 explain 2% of non-BRCA1/2 HBOC families. Thus, there is an important connection between FA and BRCA pathways. In a previous case-control association study analysing FANCA, FANCD2 and FANCL, we reported an association between FANCD2 and sporadic breast cancer (BC) risk (OR = 1.35). In order to know whether variants in other FA genes could also be involved in this association, we have extended our study with the rest of FA genes and some others implicated in the BRCA pathway. We have also analyzed the correlation with survival, nodal metastasis and hormonal receptors (ER- and PR-). A total of 61 SNPs in ten FA genes (FANC-B, -C, -D1, -E, -F, -G, -I, -J, -M, -N) and five FA related genes (ATM, ATR, BRCA1, H2AX and USP1) were studied in a total of 547 consecutive and nonrelated sporadic BC cases and 552 unaffected controls from the Spanish population. Association analyses reported marginal statistically significant results with the minor allele of intronic SNPs in three genes: BRCA1, BRCA2/FANCD1, and ATM. Survival association with SNPs on FANCC and BRCA2/FANCD1 genes were also reported. Sub-group analyses revealed associations between SNPs on FANCI and ATM and nodal metastasis status and between FANCJ/BRIP1 and FANCN/PALB2 and PR- status.

Leukopenia in kidney transplant patients with the association of valganciclovir and mycophenolate mofetil.

Cytomegalovirus (CMV) is the most common viral infection after transplantation. Valganciclovir (VGC) is established for prophylaxis and treatment of CMV infections, but leukopenia which appears in 10% to 13% (severe in 4.9%) is the principal side effect. We have recently noted an increased incidence of leukopenia and severe neutropenia among our renal transplant patients and thought to identify the associated factors. We conducted a retrospective analysis of all kidney transplantations performed between January 2005 and December 2006. All patients received mycophenolate mofetil (MMF), tacrolimus, and steroids. VGC was used for targeted prophylaxis and preemptive therapy of CMV infection, with doses adjusted to renal function. Of the 64 patients undergoing renal transplantation 13 (20.3%) developed leukopenia within 3 +/- 2 months after transplantation with severe neutropenia in 5 (7.8%). All patients were on MMF and VGC (VGC 605 +/- 296 mg/d). Leukopenia was significantly associated with simultaneous liver-kidney transplantation and with second kidney transplantations (P < .01). The incidence of leukopenia was higher among patients under VGC since day 1 of transplantation (P = .008) with maximal incidence observed among patients prescribed 900 mg/d as opposed to those on lower doses (P < .01). There was no increase in CMV infection among patients with a low dose of VGC. No patient developed clinical CMV disease. In conclusion, VGC prophylaxis was associated with an increased frequency of leukopenia on MMF-tacrolimus treated patients or regimens. Low-dose VGC for CMV prophylaxis appeared to be as effective as high-dose treatment, and associated less frequently with leukopenia and neutropenia.