Spotted fever rickettsioses. Study of cases reported in a secondary care pediatric hospital of northeastern Mexico, 2012-2022.

BACKGROUND: Spotted fever rickettsiosis is a serious disease with a high mortality rate if not timely detected. OBJECTIVE: To describe the characteristics of patients hospitalized for spotted fever rickettsiosis, as well as the risk factors associated with poor prognosis. MATERIAL AND METHODS: Data from medical records of patients hospitalized between August 2012 and July 2022 were collected. Variables were analyzed using Mann-Whitney's U-test, Fisher's exact test, and univariate or multivariate logistic regression analysis. RESULTS: Twenty-six patients were analyzed, among which a mortality of 57.6% was identified. In the between-group comparison, platelet count was lower in non-survivors (16.0 × 103/µL vs. 25.9 × 103/µL, p = 0.031). The percentage of surviving patients who received treatment more than 72 hours after fever onset was 45.5% (five patients) vs. 86.7% of non-survivors (13 patients) (p = 0.034). Receiving treatment 72 hours after fever onset increased by 7.09 times the probability of a fatal outcome (OR = 8.09, 95% CI = 1.1-55.8, p = 0.034). CONCLUSIONS: Starting adequate treatment 72 hours after the onset of fever may be an important risk factor for mortality, hence the importance of timely diagnosis and appropriate treatment of this disease.

ANTECEDENTES: La rickettsiosis de fiebre manchada es una enfermedad grave y con alta tasa de letalidad si no se identifica oportunamente. OBJETIVO: Describir las características de los pacientes hospitalizados por rickettsiosis de fiebre manchada, así como los factores de riesgo asociados a mal pronóstico. MATERIAL Y MÉTODOS: Se recabaron los datos del expediente clínico de pacientes hospitalizados entre agosto de 2012 y julio de 2022. Las variables se analizaron mediante prueba U de Mann-Whitney, prueba exacta de Fisher y regresión logística univariada y multivariada. RESULTADOS: Se analizaron 26 pacientes, en quienes se identificó una mortalidad de 57.6 %. En la comparación entre grupos, el número de plaquetas fue menor en los no supervivientes (16.0 × 103/µL versus 25.9 × 103/µL, p = 0.031). El porcentaje de pacientes supervivientes que recibieron tratamiento más de 72 horas después del inicio de la fiebre fue 45.5 % (cinco pacientes) versus 86.7 % de los no supervivientes (13 pacientes), p = 0.034. Recibir tratamiento después de 72 horas del inicio de la fiebre incrementó 7.09 veces la probabilidad de desenlace fatal (RM = 8.09, IC 95 % = 1.1-55.8, p = 0.034). CONCLUSIONES: Iniciar tratamiento adecuado posterior a 72 horas del inicio de la fiebre podría ser un factor de riesgo de mortalidad, de ahí que la importancia del diagnóstico oportuno y tratamiento adecuado de esta enfermedad.

[Spotted fever rickettsioses. Study of cases reported in a secondary care pediatric hospital of northeastern Mexico, 2012-2022]. / Rickettsiosis de fiebre manchada. Estudio de casos notificados en un hospital pediátrico de segundo nivel en el noreste de México, 2012-2022.

Background: Spotted fever rickettsiosis is a serious disease with a high mortality rate if not timely detected. Objective: To describe the characteristics of patients hospitalized for spotted fever rickettsiosis, as well as the risk factors associated with poor prognosis. Material and methods: Data from medical records of patients hospitalized between August 2012 and July 2022 were collected. Variables were analyzed using Mann-Whitney's U-test, Fisher's exact test, and univariate or multivariate logistic regression analysis. Results: Twenty-six patients were analyzed, among which a mortality of 57.6% was identified. In the between-group comparison, platelet count was lower in non-survivors (16.0 × 103/µL vs. 25.9 × 103/µL, p = 0.031). The percentage of surviving patients who received treatment more than 72 hours after fever onset was 45.5% (five patients) vs. 86.7% of non-survivors (13 patients) (p = 0.034). Receiving treatment 72 hours after fever onset increased by 7.09 times the probability of a fatal outcome (OR = 8.09, 95% CI = 1.1-55.8, p = 0.034). Conclusions: Starting adequate treatment 72 hours after the onset of fever may be an important risk factor for mortality, hence the importance of timely diagnosis and appropriate treatment of this disease.

Antecedentes: La rickettsiosis de fiebre manchada es una enfermedad grave y con alta tasa de letalidad si no se identifica oportunamente. Objetivo: Describir las características de los pacientes hospitalizados por rickettsiosis de fiebre manchada, así como los factores de riesgo asociados a mal pronóstico. Material y métodos: Se recabaron los datos del expediente clínico de pacientes hospitalizados entre agosto de 2012 y julio de 2022. Las variables se analizaron mediante prueba U de Mann-Whitney, prueba exacta de Fisher y regresión logística univariada y multivariada. Resultados: Se analizaron 26 pacientes, en quienes se identificó una mortalidad de 57.6 %. En la comparación entre grupos, el número de plaquetas fue menor en los no supervivientes (16.0 × 103/µL versus 25.9 × 103/µL, p = 0.031). El porcentaje de pacientes supervivientes que recibieron tratamiento más de 72 horas después del inicio de la fiebre fue 45.5 % (cinco pacientes) versus 86.7 % de los no supervivientes (13 pacientes), p = 0.034. Recibir tratamiento después de 72 horas del inicio de la fiebre incrementó 7.09 veces la probabilidad de desenlace fatal (RM = 8.09, IC 95 % = 1.1-55.8, p = 0.034). Conclusiones: Iniciar tratamiento adecuado posterior a 72 horas del inicio de la fiebre podría ser un factor de riesgo de mortalidad, de ahí que la importancia del diagnóstico oportuno y tratamiento adecuado de esta enfermedad.

Impact of the use of multiplex PCR on etiological diagnosis and treatment of acute respiratory infections in a private hospital of the north of the country.

BACKGROUND AND OBJECTIVE: Diseases of the respiratory system represent one of the leading causes of medical care and antibiotic prescriptions. Currently, new technologies are used for the diagnosis of respiratory diseases of viral origin, such as the FilmArray Respiratory Panel®, approved in 2012 by the FDA. The purpose of this study was to identify the correlation between the diagnosis and treatment of respiratory tract infections and the result of the polymerase chain reaction test for respiratory viruses. MATERIAL AND METHODS: The study is of a retrospective, cross-sectional, descriptive type. One-hundred and thirty-four patients who underwent a viral panel for respiratory viruses, which was positive for one or more viruses, were included. For all cases, the positive results of said test and the treatment received by patients were analyzed. RESULTS: Of the patients who underwent nasopharyngeal aspirate during hospitalization, 58 % received antibiotic treatment at admission, 13 % received combined treatment (antibiotic + antiviral), 27 % of the patients received symptomatic treatment since admission and 2 % did it with antivirals. After receiving a positive result for respiratory viruses, 38 % continued with antibiotics, 30 % with antibiotics and antivirals, 13.8 % were managed only with antivirals and 18.2 % with symptomatic treatment. CONCLUSION: Despite the global alert regarding antimicrobial resistance, patients continue to be treated with antibiotics, due to a situation that we ignore, but that is believed to be influenced by several factors.

ANTECEDENTES Y OBJETIVO: Las enfermedades del sistema respiratorio son causa frecuente de prescripción de antibióticos. Actualmente se emplean nuevas tecnologías para su diagnóstico como el FilmArray Respiratory Panel. El objetivo de este estudio es identificar la correlación entre el diagnóstico y tratamiento de infecciones de vías respiratorias con el resultado de PCR para virus respiratorios. MATERIAL Y MÉTODOS: Estudio descriptivo, transversal, retrospectivo, se incluyeron 134 pacientes atendidos en el Hospital Christus Muguerza en Saltillo, Coahuila. Para todos los casos se analizaron los resultados del panel y el tratamiento que recibieron los pacientes. RESULTADOS: El 58 % recibió tratamiento antibiótico a su ingreso, el 13 % tratamiento combinado (antibiótico + antiviral), 27 % recibió tratamiento sintomático y el 2 % fue tratado con antiviral de primera instancia. Posterior al resultado el 38 % continuó con antibiótico, el 30 % con antibiótico y antiviral, 13.8 % se manejó con antiviral y el 18.2 % con tratamiento sintomático. CONCLUSIÓN: A pesar de la alerta mundial por la resistencia a los antimicrobianos se sigue tratando a los pacientes con antibióticos, por una situación que se cree está influenciada por varios factores.

History of influenza immunization in COVID-19 patients: impact on mortality.

INTRODUCTION: In the context of the COVID-19 pandemic, there is concern regarding the impact of the influenza season. OBJECTIVE: To analyze the impact of influenza immunization history on patients with SARS-CoV-2 infection. METHODS: Patients older than 18 years with COVID-19, registered between March and August 2020, were included. Data were analyzed using Fisher's exact test and Student's t-test. To evaluate the impact on mortality, a logistic regression model was used; the relationship between the percentage of patients who received the influenza vaccine and mortality was determined with Pearson's correlation coefficient. RESULTS: 16,879 participants were included; 17 % had a history of influenza vaccination. Mortality was lower in the group with a history of vaccination (3.5 % vs. 7 %, p < 0.0001). The vaccination rate had an inverse relationship with the mortality rate (Pearson's r: -0.922, p = 0.026). CONCLUSIONS: Previous influenza immunization was an independent protective factor for mortality in patients with COVID-19. Although further studies are needed to determine a causal relationship, it would be reasonable to increase influenza immunization in the general population.

INTRODUCCIÓN: En el contexto de la pandemia de COVID-19 existe inquietud en cuanto al impacto de la temporada de influenza. OBJETIVO: Analizar el impacto del antecedente de inmunización contra influenza en pacientes con infección por SARS-CoV-2. MÉTODOS: Se incluyeron pacientes mayores de 18 años con COVID-19, registrados entre marzo y agosto de 2020. Los datos fueron analizados mediante las pruebas exacta de Fisher y t de Student. Para evaluar el impacto en la mortalidad se utilizó un modelo de regresión logística; la relación entre el porcentaje de pacientes a quienes se aplicó la vacuna contra la influenza y la mortalidad fue determinada con el coeficiente de correlación de Pearson. RESULTADOS: Se incluyeron 16 879 participantes; 17 % tuvo antecedente de vacunación contra influenza. La mortalidad fue menor en el grupo con historia de vacunación (3.5 % versus 7 %, p < 0.0001). El porcentaje de vacunación presentó una relación inversa con el porcentaje de mortalidad (r de Pearson ­ 0.922, p = 0.026). CONCLUSIONES: La inmunización contra la influenza fue un factor protector independiente de mortalidad en pacientes con COVID-19. Aunque son necesarios más estudios para determinar la relación causal, será razonable incrementar la inmunización contra influenza en la población general.

Trypanosoma cruzi induces cellular proliferation in the trophoblastic cell line BeWo.

Congenital transmission of Trypanosoma cruzi (T. cruzi) is partially responsible for the progressive globalization of Chagas disease. During congenital transmission the parasite must cross the placental barrier where the trophoblast, a continuous renewing epithelium, is the first tissue in contact with the parasite. The trophoblast turnover implies cellular proliferation, differentiation and apoptotic cell death. The epithelial turnover is considered part of innate immunity. We previously demonstrated that T. cruzi induces cellular differentiation and apoptosis in this tissue. Here we demonstrate that T. cruzi induces cellular proliferation in a trophoblastic cell line. We analyzed the cellular proliferation in BeWo cells by determining DNA synthesis by BrdU incorporation assays, mitotic index, cell cycle analysis by flow cytometry, as well as quantification of nucleolus organizer regions by histochemistry and expression of the proliferation markers PCNA and Ki67 by Western blotting and/or immunofluorescence. Additionally, we determined the ERK1/2 MAPK pathway activation by the parasite by Western blotting.

Micellar electrokinetic chromatographic method for the dabrafenib determination in biological samples.

Two different micellar electrokinetic chromatographic methods to determine dabrafenib in urine and serum, both using borate buffer (pH 9.2, 20 mM) and SDS as separation electrolyte, are developed and validated. The analyses were carried out in a fused-silica capillary of 75 µm of internal diameter and total length of 47 and 37 cm for urine and serum determination, respectively. The detection of the target compound was performed at 227 nm in urine samples and at 251 nm in serum samples. The linearity range was from 1 to 21 mg/L of dabrafenib in urine and from 2 to 40 mg/L in serum. In all cases, inter- and intraday RSDs were <4%. Sample preparation of serum samples consists of an only step of 1:1 dilution with water before its injection in the electrophoretic system. These simple, sensitive, accurate, and cost-effective methods can be used in routine clinical practice to monitor dabrafenib concentrations in urine and serum of metastatic melanoma skin cancer patients.

A local innate immune response against Trypanosoma cruzi in the human placenta: The epithelial turnover of the trophoblast.

Congenital Chagas disease, caused by Trypanosoma cruzi, is partially responsible for the progressive globalization of Chagas disease despite of its low transmission rate. The probability of congenital transmission depends on complex interactions between the parasite, the maternal and fetus/newborn immune responses and placental factors, being the latter the least studied one. During transplacental transmission, the parasite must cross the placental barrier where the trophoblast, a continuous renewing epithelium, is the first tissue to have contact with the parasite. Importantly, the epithelial turnover is considered part of the innate immune system since pathogens, prior to cell invasion, must attach to the surface of cells. The trophoblast turnover involves cellular processes such as proliferation, differentiation and apoptotic cell death, all of them are induced by the parasite. In the present review, we analyze the current evidence about the trophoblast epithelial turnover as a local placental innate immune response.

Caspase-8 activity is part of the BeWo trophoblast cell defense mechanisms against Trypanosoma cruzi infection.

Congenital Chagas disease is caused by the protozoan parasite Trypanosoma cruzi that must cross the placental barrier during transmission. The trophoblast constitutes the first tissue in contact with the maternal-blood circulating parasite. Importantly, the congenital transmission rates are low, suggesting the presence of local placental defense mechanisms. Cellular proliferation and differentiation as well as apoptotic cell death are induced by the parasite and constitute part of the epithelial turnover of the trophoblast, which has been suggested to be part of those placental defenses. On the other hand, caspase-8 is an essential molecule in the modulation of trophoblast turnover by apoptosis and by epithelial differentiation. As an approach to study whether T. cruzi induced trophoblast turnover and infection is mediated by caspase-8, we infected BeWo cells (a trophoblastic cell line) with the parasite and determined in the infected cells the expression and enzymatic activity of caspase-8, DNA synthesis (as proliferation marker), ß-human chorionic gonadotropin (ß-hCG) (as differentiation marker) and activity of Caspase-3 (as apoptotic death marker). Parasite load in BeWo cells was measured by DNA quantification using qPCR and cell counting. Our results show that T. cruzi induces caspase-8 activity and that its inhibition increases trophoblast cells infection while decreases parasite induced cellular differentiation and apoptotic cell death, but not cellular proliferation. Thus, caspase-8 activity is part of the BeWo trophoblast cell defense mechanisms against T. cruzi infection. Together with our previous results, we suggest that the trophoblast turnover is part of local placental anti-parasite mechanisms.

Quantitation of sunitinib, an oral multitarget tyrosine kinase inhibitor, and its metabolite in urine samples by nonaqueous capillary electrophoresis time of flight mass spectrometry.

A rapid, sensitive, and specific method was developed and validated using a nonaqueous-capillary electrophoresis method with TOF-MS for determination of sunitinib and N-desethyl sunitinib in human urine. In order to avoid ionic suppression a urine samples dilution with methanol 1:10 previous step was used. This was the only treatment step to urine samples before the injection. Despite this dilution of the urine, the detection limit was as low as 0.07 mg/L for sunitinib and 0.15 mg/L for N-desethyl sunitinib. Separation of compounds was achieved with a mixture of 5 mM ammonium formate in methanol. The calibration curves were linear over the range of 0.5-50.0 mg/L for the two analyzed compounds. The within-run and between-run precisions were within 5%, while the accuracy ranged from 96.0 to 100.4%. This method can be used in routine clinical practice to monitor sunitinib and N-desethyl sunitinib drugs in the urine of cancer patients treated with once daily administration.

Simultaneous determination of erlotinib and metabolites in human urine using capillary electrophoresis.

The purpose of this study was to develop a simple and sensitive CE-UV method to quantify erlotinib and metabolites in urine. Following liquid-liquid extraction, erlotinib, and metabolites were separated with a BGE whose composition was phosphate buffer (pH 2.5, 65 mM) with 0.5% Tween 20. The applied voltage was 22 kV, capillary temperature 25°C and the sample injection was performed in the hydrodynamic mode. All the analyses were carried out in a fused silica capillary with an internal diameter of 75 µm and a total length of 37 cm. The detection of target compounds was performed at 240 nm. The calibration was linear in the range 0.15-20 mg/L for erlotinib and metabolites. Inter-and intraday imprecision were less than 4%. This simple, sensitive, accurate, and cost-effective method can be used in routine clinical practice to monitor erlotinib concentrations in urine from nonsmall cell lung cancer patients.

Direct determination of pregabalin in human urine by nonaqueous CE-TOF-MS.

Determination of pregabalin in urine samples was carried out by nonaqueous CE with TOF-MS via ESI, with a mixture of 10 mM ammonium formate and 0.05% acetic acid in methanol. By using TOF-MS, accurate mass information was obtained, thus causing a great improvement in qualitative ability. In order to avoid ionic suppression, urine samples dilution 1:10 was used. This was the only treatment to urine samples before the injection. Despite this dilution, the detection limit was as low as 0.03 µg/mL for pregabalin. The method was validated with respect to accuracy, precision, and linearity, LOD, and LOQ. This method was applied to the analysis of urine samples from seven different cancer patients undergoing treatment with pregabalin. The developed method may find wide application for the routine determination of pregabalin in biological samples in order to establish a more efficient and safe dosage.

Impact of insufflator/aspirator versus exclusive insufflator during robotic radical prostatectomy: a comparative prospective cohort study.

New generation devices that combine high-flow insufflation with smoke aspiration using continuous gas recirculation ]so-called Insufflator/aspirator systems (IAS)] have recently been developed to generate pneumoperitoneum. The use of an IAS could have an impact on surgical compared to conventional insufflation systems (CIS). The present study aimed to compare the clinical effectiveness/safety, healthorganizational, and pathological/oncological outcomes of the CIS versus IAS during robot-assisted radical prostatectomy (RARP). Methods: Comparative retrospective cohort study including patients with non-metastatic prostate cancer treated with RARP by four expert surgeons at a robotic referral centre between January 2020 and December 2021. A CIS was used until 15 March 2021, and the IAS thereafter. Data were extracted from the Institutional Review Board-approved (#1064) retro and prospective institutional database. Results: The final analysis included 299 patients (143 CIS; 156 IAS). We found no statistically significant differences in demographic data and preoperative results, allowing adequate group comparison. The rate of complications of any degree (9.1% and 1.9%, P<0.05) and major complications (4.2% and 0.6%, P<0.05) were lower in the IAS group. Accordingly, the hospital stay was shorter in the IAS group (P<0.05); however, the small size of this statistically significant difference probably lacks clinical value (1.9±1.6 vs. 1.6±0.8 days). There was no significant difference in surgical time, bleeding, pathological findings, or oncological results. Conclusions: Data from this large group of patients showed that the rate of overall complications, the rate of major complications, and the length of stay were lower in the IAS group. Implementing the IAS in RARP patients increased the occurrence of SCE and affected our daily practice of transversus abdominis plane block. Interpretation of the results should be made with caution since the design of this study did not allow for the identification of a causal relationship.

Determination of morphine, codeine, and paclitaxel in human serum and plasma by micellar electrokinetic chromatography.

A micellar electrokinetic chromatography method is proposed for the determination of morphine, codeine, and paclitaxel at clinical relevant levels in human serum and plasma, which are employed in the treatment of patients with cancer. Optimal conditions for the separation were investigated. A background electrolyte solutions consisting of 20 mM borate buffer adjusted to pH 8.5, sodium dodecyl sulphate 60 mM and 15% methanol, hydrodynamic injection, and 25 kV as separation voltage were used. Detection wavelength was 212 nm for morphine and codeine and 200 nm for paclitaxel. Aspects such as stability of the solutions, linearity, accuracy, precision, and robust and ruggedness were examined in order to validate the proposed method. Detection limits obtained for all the studied compounds ranged between 26 and 52 ng/mL. Before micellar electrokinetic chromatography determination, the samples were purified and enriched by means of an extraction-preconcentration step with a preconditioned C(18) cartridge. This method was applied to the analysis of serum and plasma samples from different cancer patients undergoing treatment with paclitaxel or/and codeine.

Generation of an induced pluripotent stem cell line (UNCCi002-A) from a healthy donor using a non-integration system to study Cerebral Cavernous Malformation (CCM).

The generation of induced pluripotent stem cells (iPSCs) from healthy individuals is an invaluable resource as reference control in disease modeling and drug discovery. This paper details the reprogramming of peripheral blood mononuclear cells (PBMCs) isolated from a healthy 27 years-old male using non-integration technology. The derived iPSCs displayed typical pluripotent stem cell morphology, the capacity to differentiate into the three germ layers, and normal karyotype. This iPSC line will be used as a reference control to study the Cerebral Cavernous Malformation disease mechanism.

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.

SPTBN1 encodes ßII-spectrin, the ubiquitously expressed ß-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal ßII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect ßII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of ßII-spectrin in the central nervous system.

Simplified medication regimen and survival in polypathological patients. / Simplicidad del régimen de medicación y supervivencia en pacientes pluripatológicos.

OBJECTIVE: To determine if a more simplified medication regimen is associated with survival in polypathological patients. METHODS: Multicentre cohort study. We included polypathological patients admitted to internal medicine wards between March 1st and June 30rd, 2011. Patients that died during admission and readmissions were excluded. Data were collected about age, gender, home, comorbidity, Charlson, Barthel and Lawton-Brody indexes, Short Portable Mental State Questionnaire, socio-familial Gijón scale, admissions in the previous year, delirium, need of a caregiver and PROFUND index. The therapy complexity was measured with the Medication Regimen Complexity Index. The follow-up lasted 4-years. To determine the factors associated with mortality we performed a Cox proportional regression model. RESULTS: Overall 223 polypathological patients were included, with a mean age of 79.8 (8.6) years. Mean score in Medication Regimen Complexity Index was 32.0 (15.2). After 4 years, 161 (72.2%) patients died, 36 with a more simplified medication regimen. Age (HR 1.060, 95%CI 1.032-1.089; P<.001), neoplasms (HR 2.477, 95%CI 1.564-3.923; P<.001), and the number of admissions in the previous year (HR 1.251, 95%CI 1.100-1.423; P=.001) were independently associated with 4-year mortality, and Barthel index score (HR .991, 95%CI .983-0.998; P<.001) and a more simplified medication regimen (HR 0.634 95%CI 0.414-.970; p=.036) with lower mortality. CONCLUSIONS: In polypathological patients, the more simplified medication regimens are associated with a lower mortality.

Acute kidney injury and cholestasis associated with Kawasaki disease in a 9-year-old: Case report. / Daño renal agudo y colestasis asociados a la enfermedad de Kawasaki en una paciente de 9 años; reporte de caso.

Kawasaki disease (KD) is a systemic vasculitis frequent in children younger than 5 years of age. It involves coronary arteries and other medium-sized vessels. There also exists evidence of inflammatory and proliferative changes affecting the biliary tract and lymphocyte infiltration of the renal interstitial. We describe the case of a 9-year-old girl who developed high-grade fever, bilateral non-purulent conjunctivitis, «strawberry¼ tongue, desquamation of the fingers and toes, cholestatic syndrome, edema and elevated serum creatinine. KD is a diagnostic challenge for the pediatrician. In every patient with high-grade fever, cholestasis and acute kidney injury, KD should be included in the differential diagnosis, even though more research is necessary to evaluate this atypical association.

Common B-cell acute lymphoblastic leukaemia in a 70-year-old woman presenting 2 years after carboplatin-taxane radiotherapy for endometrial cancer.

Therapy-related acute lymphoblastic leukaemia (t-ALL) is a poorly defined entity and is not featured in the World Health Organization classification as a distinct clinical entity from acute lymphoblastic leukaemia (ALL), thus differing from therapy-related acute myeloid leukaemia and myelodysplasia. We present a case of t-ALL occurring 18 months after treatment for metastatic endometrial cancer with a regimen of carboplatin, paclitaxel and radiotherapy. The patient presented with severe pancytopenia and diagnosed with common-B ALL, and the cytogenetic analysis showed a previously unreported deletion in chromosome 19 (q13.1) in 100% of the blast cells. The patient declined further therapy and died 1 month later. This rare but serious side effect of chemo-radiotherapy should be considered when deciding on treatment options for gynaecological cancers.

Predictive Value of Neutrophil to Lymphocyte Ratio in the Diagnosis of Significant Prostate Cancer at Initial Biopsy: A Comparison with Free Percent Prostate Specific Antigen, Prostate Specific Antigen Density and Primary Circulating Prostate Cells.

INTRODUCTION: An elevated serum PSA is the only biomarker routinely used in screening for prostate cancer to indicate a prostate biopsy. However, it is not specific for prostate cancer and the neutrophil/lymphocyte ratio has been suggested as an alternative. We present a prospective study of men with an elevated PSA and compare the neutrophil/lymphocyte ratio, free percent PSA, PSA density and the presence of circulating prostate cells to detect clinically significant prostate cancer at first biopsy. PATIENTS AND METHODS: Prospective study of consecutive men with a PSA 4-10 ng/ml referred for initial prostate biopsy, the results were compared with the neutrophil/lymphocyte ratio, free percent PSA and PSA density. Circulating prostate cells (CPCs) were detected using immunocytochemistry. The blood sample was taken immediately before the prostate biopsy. RESULTS: 1,223 men participated, 38% (467) of whom had prostate cancer detected, of these 322 were clinically significant. The area under the curves were for neutrophil/lymphocyte ratio, free percent PSA, PSA density and CPC detection were 0.570, 0.785, 0,620 and 0.844 respectively. Sensitivity/specificity were 0.388/0.685, 0.419/0.897, 0.598/0.624 and 0.966/0.786 respectively. The neutrophil/lymphocyte ratio did not differentiate between benign and malignant disease. CONCLUSIONS: The neutrophil/lymphocyte ratio did not discriminate between benign and malignant prostatic disease in patients with a PSA between 4-10ng/ml.

Effect of FOLFOX on minimal residual disease in Stage III colon cancer and risk of relapse.

INTRODUCTION: 25% of Stage III colon cancer patients relapse within 5 years due to minimal residual disease (MRD) not eliminated by surgery and chemotherapy. We hypothesise that sub-types of MRD, defined by circulating tumour cells (CTCs) and bone marrow micro-metastasis (mM) have different types and kinetics of relapse. PATIENTS AND METHODS: One month of curative surgery and 1 month after completing six cycles of FOLFOX chemotherapy blood and bone marrow samples were taken to detect CTCs and mM using immunocytochemistry with anti-carcino-embryonic antigen (CEA). Follow up was up to 5 years or disease progression defined as new images on CT scanning. Survival curves using Kaplan-Meier (KM) and Restricted Mean Survival Time (RMST) were calculated for three prognostic groups: CTC and mM negative, CTC negative mM positive, and CTC positive. RESULTS: 76 patients (39 men) participated, mean age 67 years, median follow-up 3.6 years. The response to chemotherapy was heterogeneous and MRD pre-treatment did not predict response to therapy. Of 21 patients MRD (-), 20 remained MRD negative and one patient became mM (+); of 21 patients mM (+), 10 became MRD (-), 8 remained the same and 3 became CTC (+); of the 34 CTC positive, 8 became MRD (-), 8 with only mM, and 18 remained positive.After chemotherapy, 38 patients were negative for CTC and mM, 17 were positive for only mM, and 21 for CTCs. For the whole cohort, the 5 year KM was 58%, the median survival was not reached. For the three prognostic groups, the KM 5-year survivals were 87%, 58%, and 4%, respectively, the median survival for patients MRD negative and mM only was not reached. RMST for the whole cohort was 3.6 years, for the three prognostic groups the RMST was 4.6 years, 4.0 years, and 1.5 years, respectively. Serum CEA was significantly higher pre-surgery in the CTC positive group. There were no significant differences with respect to age or sex between the three groups. CONCLUSIONS: MRD subtypes pre-chemotherapy did not predict treatment response. Post-chemotherapy MRD subtypes were associated with the pattern of failure and time to failure. MRD negative patients had an excellent prognosis with 87% disease-free survival at 5 years. Those with only mM had a similar outcome up to 2 years and then were at increasing risk of late failure. Patients who were CTC positive had a high risk of early failure. MRD subclassification may be useful to define the risk of relapse in Stage III colon cancer patients and warrants further studies with a larger number of patients.