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OBJECTIVE: To compare the extent of cytopenias and systemic immune inflammation index of hospitalised coronavirus disease-2019 patients during the first and second/third waves of the pandemic. Methods: The retrospective, cross-sectional study was conducted in October 2021 at Fatima Memorial Hospital, Lahore, Pakistan, and comprised data of hospitalised coronavirus disease-2019 patients regardless of age and gender from May 2020 to June 2021. Data was segregated into first wave that lasted from May to July 2020, second wave that lasted from early November to mid-December 2020, and third wave that ranged from mid-March to June 2021. For comparison purposes, the data of first wave was in group A, while data of second and third waves was pooled into group B. Age, gender, comorbidities, requirement of ventilator support and outcome of the patients was noted. Inflammatory markers were compared on the basis of complete blood count and systemic immune-inflammation index data. Data was analysed using SPSS 25. RESULTS: Of the 202 patients, 90(44.5%) were in group A and 112(55.4%) were in group B. There were 108(53.5%) males and 94(46.5%) females. The median age in males was 58 years (interquartile range: 21 years) and it was 56 years (interquartile range: 21 years) in females. Neutrophilia (p<0.001), leukocytosis (p<0.001) and lymphocytopenia (p<0.001) had direct association with increased systemic immune-inflammation. Raised systemic immune-inflammation also had an association with increased requirement of ventilator support (p=0.2) and increased mortality (p=0.001). There were more females, more critical patients, more patients with anaemia, leukopenia, lymphocytopenia and thrombocytopenia in group B compared to group A (p<0.05). Need for ventilator support and mortality were also higher in group B compared to group A (p<0.05). Conclusion: All the indicators analysed were worse during the second and third waves of coronavirus disease-2019 compared to the first wave of the pandemic.
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COVID-19 , SARS-CoV-2 , Trombocitopenia , Humanos , COVID-19/inmunología , COVID-19/terapia , COVID-19/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Transversales , Pakistán/epidemiología , SARS-CoV-2/inmunología , Adulto , Anciano , Trombocitopenia/epidemiología , Trombocitopenia/inmunología , Hospitalización/estadística & datos numéricos , Leucopenia/epidemiología , Linfopenia/inmunología , Respiración Artificial/estadística & datos numéricos , Inflamación/inmunología , CitopeniaRESUMEN
BACKGROUND: The current prediction models for the risk of infection during immunosuppressive treatment for lupus nephritis (LN) lack a prediction time window and have poor pertinence. This study aimed to develop a risk stratification to predict infection during immunosuppressive therapy in patients with LN. METHODS: This retrospective nested case-control study collected patients with LN treated with immunosuppressive therapy between 2014 and 2022 in the Nephrology ward in Huashan Hospital affiliated to Fudan University and Huashan Hospital Baoshan Branch. Cases were defined as patients who experienced infection during the follow-up period; patients were eligible as controls if they did not have infection during the follow-up period. RESULTS: There were 53 patients with infection by CTCAE V5.0 grade ≥2. According to the 1:3 nested matching, the 53 patients with infection were matched with 159 controls. In the multivariable logistic regression model, the change rate of fibrinogen (OR = 0.97, 95% CI: 0.94-0.99, p = 0.008), leukopenia (OR = 8.68, 95% CI: 1.16-301.72, p = 0.039), and reduced albumin (OR = 6.25, 95% CI: 1.38-28.24, p = 0.017) were independently associated with infection. The AUC of the ROC curve in the validation set of the multivariable logistic regression model in the internal random sampling was 0.864. The scores range from -2 to 10. The infection risk stratification ranges from 2.8% at score -2 to 97.5% at score 10. CONCLUSION: A risk stratification was built to predict the risk of infection in patients with LN undergoing immunosuppressive therapy.
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Inmunosupresores , Nefritis Lúpica , Humanos , Nefritis Lúpica/tratamiento farmacológico , Femenino , Masculino , Estudios Retrospectivos , Adulto , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Estudios de Casos y Controles , Medición de Riesgo , Persona de Mediana Edad , Factores de Riesgo , Infecciones/epidemiología , Infecciones/etiología , Modelos Logísticos , Curva ROC , Adulto Joven , Leucopenia/inducido químicamente , Leucopenia/epidemiologíaRESUMEN
Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy. The primary end point was the incidence of 6-MP myelosuppression in both groups. Secondary end points included frequencies of 6-MP hepatotoxicity, duration of myelosuppression and leukopenia, event-free survival, and steady-state concentrations of active metabolites (6-thioguaninenucleotides and 6-methylmercaptopurine nucleotides) in erythrocytes. A 2.2-fold decrease in myelosuppression, the primary end point, was observed in the gene-based-dose group using ~ 50% of the standard initial 6-MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene-based-dose group had a significantly lower risk of developing thiopurine-induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady-state concentrations of active metabolites in erythrocytes between the two groups. TPMT- and NUDT15-based dosing of 6-MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.
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Pueblos del Este de Asia , Mercaptopurina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Antimetabolitos Antineoplásicos/efectos adversos , Enfermedades de la Médula Ósea , Enfermedad Hepática Inducida por Sustancias y Drogas , China/epidemiología , Leucopenia/inducido químicamente , Leucopenia/epidemiología , Mercaptopurina/efectos adversos , Metiltransferasas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologíaRESUMEN
OBJECTIVE: This study determined the impact of demographic factors, clinical manifestations, disease activity, and serological tests at baseline on future SLE development in Sjögren's syndrome (SS) patients. METHODS: This retrospective study assessed 1,082 SS patients without other autoimmune diseases at baseline who visited our hospital between January 2012 and March 2021. We analyzed demographic features, extra-glandular manifestations (EGMs), clinical indices, and laboratory values at baseline between the two groups divided per future SLE development (SS/SLE group vs SS group). The probability and predictors of SLE development in SS patients were estimated using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The median follow-up duration was 1083.5 days. Forty-nine patients (4.5%) developed SLE that met the 2012 Systemic Lupus International Collaborating Clinics or 2019 EULAR/ACR classification criteria. The baseline EULAR SS disease activity index (ESSDAI) score was significantly higher in the SS/SLE group (p < .001). The SS/SLE group had more lymphadenopathy and renal involvement (p = .015 and p = .017, respectively). Shorter SS disease duration (<3 years) (hazard ratio [HR] = 2.12, p = .0328), high ESSDAI (HR = 8.24, p < .0001), leukopenia (HR = 4.17, p = .0005), thrombocytopenia (HR = 3.38, p = .0059), hypocomplementemia (HR = 29.06, p<.0001), and positive for anti-dsDNA (HR = 13.70, p < .0001), anti-ribonucleoprotein (RNP) (HR = 3.82, p = .0027), and anti-ribosomal P (HR = 6.70, p = .0002) at baseline were SLE development predictors in SS patients. CONCLUSION: Shorter disease duration and higher disease activity of SS at baseline may be risk factors for future SLE development. Serologic predictors of SLE development are hypocomplementemia, leukopenia, thrombocytopenia, and positivity for anti-dsDNA, anti-RNP, and anti-ribosomal P antibodies. If the above factors are observed, close monitoring will be necessary during the follow-up period, considering the possibility of future SLE development.
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Leucopenia , Lupus Eritematoso Sistémico , Síndrome de Sjögren , Trombocitopenia , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Estudios Retrospectivos , Leucopenia/epidemiología , Leucopenia/etiología , Anticuerpos Antinucleares , Trombocitopenia/complicaciones , República de Corea/epidemiologíaRESUMEN
BACKGROUND AND AIMS: Nudix hydrolase 15 [NUDT15] genetic variants confer an increased risk of thiopurine-induced leukopenia [TIL]; however, their global prevalence in inflammatory bowel disease [IBD] patients is unknown. We aimed to evaluate the global prevalence of NUDT15 variants in IBD patients and incidence of TIL in these patients. METHODS: Six databases were searched from inception until July 2022. Studies reporting the frequency of any NUDT15 variant and/or frequency of leukopenia in adult IBD patients with these variants were included. A random effects model was performed to estimate the pooled prevalence of variants, incidence of early [≤8 weeks] and late [>8 weeks] leukopenia, and relative risk of developing leukopenia. RESULTS: Twenty studies comprising 5232 patients were included. The pooled prevalence of the *1/*3 c.415Câ >â T C/T diplotype was 13% (95% confidence interval [CI]: 10-18%), *3/*3 c.415Câ >â T T/T diplotype was 2% [95% CI: 1-2%], *1/*5 c.52Gâ >â A G/A diplotype was 2% [95% CI: 1-3%], and *1/*6 c.36_37insGGAGTC ins/- diplotype was 7% [95% CI: 4-12%]. The pooled prevalence of *1/*3 was high in Japanese [20%, 95% CI: 16-24%] and Chinese patients [18%, 95% CI: 12-27%]. The incidence of early leukopenia was 20% [95% CI: 16-26%] in *1/*3 patients, 99% [95% CI: 7-100%] in *3/*3 patients, and 49% [95% CI: 29-69%] in *1/*6 patients. The incidence of late leukopenia was 36% [95% CI: 26-49%] in *1/*3 patients. CONCLUSIONS: NUDT15 variants are common and strongly predict TIL in IBD patients. Pre-treatment NUDT15 genotyping should be considered particularly in Asian populations, to guide thiopurine dosing and prevent myelotoxicity.
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Enfermedades Inflamatorias del Intestino , Leucopenia , Purinas , Compuestos de Sulfhidrilo , Adulto , Humanos , Mercaptopurina/efectos adversos , Incidencia , Prevalencia , Predisposición Genética a la Enfermedad , Factores de Riesgo , Pirofosfatasas/genética , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/inducido químicamente , Leucopenia/inducido químicamente , Leucopenia/epidemiología , Leucopenia/genéticaRESUMEN
The objective of this study was to evaluate the prevalence and the clinical significance of lymphadenopathy and its histological subtypes in patients with systemic lupus erythematosus. We conducted a retrospective cohort study of patients with SLE diagnosed using the 1997 ACR criteria, who were followed at our institution between 2008 and 2022. Patients were grouped based on the presence of SLE-attributed LAD and its histological phenotype, then compared in terms of demographic, clinical and laboratory characteristics. Of the 255 patients, 33.7% had SLE-attributed, 0.8% lymphoma-related and 0.4% tuberculosis-related LAD. Univariate analysis identified significant associations between the presence of LAD and fever (p < 0.0001), weight loss (p = 0.009), pericarditis (p = 0.004), myocarditis (p = 0.003), myositis (p = 0.034), leukopenia (p = 0.004), lymphopenia (p = 0.003), membranous nephritis (p = 0.004), anti-RNP (p = 0.001), anti-Smith (p = < 0.0001), and SSB antibodies (p = 0.038), and hypocomplementemia (C3:p = 0.019; C4:p < 0.0001). Logistic regression confirmed the associations of LAD with fever (OR = 3.277, 95% C.I 1.657-6.481), pericarditis (OR = 4.146, 95% C.I:1.577-10.899), membranous nephritis (OR = 3.586, 95% C.I:1.305-9.854), and leukopenia (OR = 2.611, 95%C.I:1.319-5.166), but not with weight loss, myocarditis, or myositis. Biopsy in a subset of patients (33.7% of total) revealed reactive/proliferative (62.1%) or necrotizing (37.9%) histological patterns. When we compared the histologic patterns, necrotizing LAD was associated with fever (p = 0.052), sicca (p = 0.018), and malar rash (p = 0.005). Most patients received corticosteroids, hydroxychloroquine, and/or DMARDs with relatively quick clinical improvement. In conclusion, LAD is a common SLE manifestation, associated with constitutional symptoms, myo-/pericarditis, myositis, cytopenia, and membranous nephritis. Despite relatively high prevalence of LAD in SLE, a biopsy may still be needed to rule out lymphoma.
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Leucopenia , Lupus Eritematoso Sistémico , Linfadenopatía , Miocarditis , Miositis , Nefritis , Pericarditis , Humanos , Prevalencia , Estudios Retrospectivos , Relevancia Clínica , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Pericarditis/complicaciones , Pericarditis/epidemiología , Linfadenopatía/complicaciones , Leucopenia/epidemiología , Leucopenia/complicaciones , Miositis/complicaciones , Nefritis/complicacionesRESUMEN
BACKGROUND: Leukopenia in the early period following heart transplantation (HT) is not well-studied. The aim of this study was to evaluate risk factors for the development of post-transplant leukopenia and its consequences for HT recipients. METHODS: Adult patients at a large-volume transplant center who received HT between January 1, 2010 and December 31, 2020 were included. The incidence of leukopenia (WBC ≤3 × 103 /µL) in the first 90-days following HT, individual risk factors, and its effect on 1-year outcomes were evaluated. RESULTS: Of 506 HT recipients, 184 (36%) developed leukopenia within 90-days. Median duration of the first leukopenia episode was 15.5 days (IQR 8-42.5 days). Individuals who developed leukopenia had lower pre-transplant WBC counts compared to those who did not (6.1 × 103 /µL vs. 6.9 × 103 /µL, p = .02). Initial immunosuppressive and infectious chemoprophylactic regimens were not significantly different between groups. Early leukopenia was associated with a higher mortality at 1-year (6.6% vs. 2.1%, p = .008; adjusted HR 3.0) and an increased risk of recurrent episodes. Rates of infection and rejection were not significantly different between the two groups. CONCLUSIONS: Leukopenia in the early period following HT is common and associated with an increased risk of mortality. Further study is needed to identify individuals at highest risk for leukopenia prior to transplant and optimize immunosuppressive and infectious chemoprophylactic regimens for this subgroup.
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Trasplante de Corazón , Trasplante de Riñón , Leucopenia , Adulto , Humanos , Trasplante de Riñón/efectos adversos , Leucopenia/epidemiología , Leucopenia/etiología , Inmunosupresores/efectos adversos , Factores de Riesgo , Trasplante de Corazón/efectos adversos , Receptores de Trasplantes , Rechazo de Injerto/epidemiología , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Estudios RetrospectivosRESUMEN
AIM: Few data are available regarding the management of anorectal abscess in patients with leukopenia. The aim of this study was to investigate the impact of leukopenia among patients undergoing incision and drainage for anorectal abscess. METHOD: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database identified patients from 2015 to 2020. Perianal fistulas and supralevator abscesses were excluded. Patients were grouped based on white blood cell (WBC) count: WBC < 4.5 cells/µl, WBC = 4.5-11.0 cells/µl and WBC > 11.0 cells/µl. The 30-day overall complications and outcomes were compared using regression models, accounting for demographics and comorbidities. RESULTS: Ten thousand two hundred and forty (70.3% male) patients were identified. Univariate analysis showed that, compared with patients with leukocytosis (WBC > 11.0 cells/µl) and normal WBC count (WBC = 4.5-11.0 cells/µl), patients with leukopenia (WBC <4.5 cells/µl) had higher rates of overall (p < 0.001), pulmonary (p < 0.001) and haematological complications (p < 0.001). They also had higher rates of readmission (p < 0.001), reoperation (p = 0.005), discharge to a care facility (p = 0.003), increased length of hospital stay (p = 0.004) and death (p < 0.001). Multivariable analysis identified leukopenia as an independent risk factor for overall complications [odds ratio (OR) 2.31, 95% CI 1.65-3.24; p < 0.001], pulmonary complications (OR 5.65, 95% CI 1.88-16.97; p = 0.002), haematological complications (OR 4.30, 95% CI 2.94-6.28; p < 0.001), unplanned readmission (OR 2.20, 95% CI 1.43-3.40; p < 0.001), reoperation (OR 1.80, 95% CI 1.10-2.93; p = 0.019) and death (OR 2.77, 95% CI 1.02-7.52; p = 0.046). Discharge to a care facility and length of stay were not significant on multivariable analysis. CONCLUSION: Leukopenia is associated with increased risk for pulmonary and haematological complications, readmissions, reoperations, discharge to a care facility and death after incision and drainage for anorectal abscess.
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Enfermedades del Ano , Leucopenia , Humanos , Masculino , Femenino , Absceso/etiología , Absceso/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Enfermedades del Ano/cirugía , Estudios Retrospectivos , Leucopenia/epidemiología , Leucopenia/etiología , Readmisión del Paciente , DrenajeRESUMEN
Azathioprine (AZA) is commonly used for many autoimmune disorders; however, the limitation of its clinical use is due to potential toxicities, including severe leukopenia. Recent studies have identified genetic NUDT15 variants strongly associated with AZA-induced leukopenia in Asian patients. This study aimed to investigate the strength of above genetic association and evaluate the usefulness of prospective screening of the NUDT15 variants to prevent AZA-induced leukopenia in Chinese patients. AZA-induced leukopenia in patients with autoimmune disorders were enrolled from multiple medical centers in Taiwan/China between 2012 and 2017 to determine the strength of genetic association of NUDT15 or TPMT variants by whole exome sequencing (WES). Furthermore, a prospective study was conducted between 2018 and 2021 to investigate the incidence of AZA-induced leukopenia with and without genetic screening. The WES result showed the genetic variants of NUDT15 R139C (rs116855232) (P = 3.7 × 10-25 , odds ratio (OR) = 21.7, 95% confidence interval (95% CI) = 12.1-38.8) and NUDT15 rs746071566 (P = 4.2 × 10-9 , OR = 7.1, 95% CI = 3.7-13.7), but not TPMT, were associated with AZA-induced leukopenia and NUDT15 R139C variant shows the highest sensitivity with 92.5%. Furthermore, the targeted screening of 1,013 participants for NUDT15 R139C enabled those identified as carriers to use alternative immunosuppressants. This strategy resulted in a significant decrease in the incidence of AZA-induced leukopenia compared with historical incidence (incidence rate = from 7.6% decreased to 0.4%; P = 9.3 × 10-20 ). In conclusion, the NUDT15 R139C variant was strongly associated with AZA-induced leukopenia in Chinese patients. The genetic screening of NUDT15 R139C followed by use of alternative immunosuppressants in identified carriers effectively decreased the incidence of AZA leukopenia for patients with autoimmune disorders.
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Enfermedades Autoinmunes , Leucopenia , Trombocitopenia , Humanos , Azatioprina/efectos adversos , Estudios Prospectivos , Genotipo , Pirofosfatasas/genética , Leucopenia/inducido químicamente , Leucopenia/epidemiología , Leucopenia/genética , Inmunosupresores/efectos adversos , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/epidemiología , Metiltransferasas/genéticaRESUMEN
OBJECTIVE: To examine serum C-reactive protein levels and the prevalence of leukopenia in patients with Crohn's disease or ulcerative colitis undergoing treatment with azathioprine and/or mesalazine. METHODS: Retrospective observational study based on clinical and laboratory data collected from medical records of 76 adult patients with inflammatory bowel disease treated with azathioprine, mesalazine or both. Sex, age, diagnosis, number of blood samples and elevated serum C-reactive protein levels during the follow-up period were recorded. The following variables were analyzed in terms of C-reactive protein levels and leukopenia episodes: sex, age, diagnosis of inflammatory bowel disease and type of drug. Statistical analyses included multiple logistic regression and the Fisher's exact test for qualitative variables. RESULTS: Leukopenia was observed in 18.4% of patients and was associated with older age and higher doses of medication. In 44% of patients, C-reactive protein levels were high. However, symptoms were not associated with abnormal levels of this marker. CONCLUSION: Regardless of symptoms, serum C-reactive protein levels were not a reliable indicator of controlled inflammatory bowel disease. Leukopenia was independently associated with older age and higher doses of medication and is a common side effect, which should be routinely monitored.
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Enfermedades Inflamatorias del Intestino , Leucopenia , Adulto , Azatioprina/efectos adversos , Proteína C-Reactiva , Humanos , Enfermedades Inflamatorias del Intestino/inducido químicamente , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/epidemiología , Leucopenia/inducido químicamente , Leucopenia/tratamiento farmacológico , Leucopenia/epidemiología , Mesalamina/efectos adversos , PrevalenciaRESUMEN
BACKGROUND: Human brucellosis is one of the most widespread zoonotic diseases that are presented with predominantly hematological manifestations. We aimed to evaluate the hematological findings of childhood brucellosis and to determine the predictive clinical findings and laboratory tests that might be related to hematologic involvement. METHODS: We retrospectively analyzed the medical records of children with brucellosis between 1 January 2005 and 31 December 2018. We compared predictive clinical and physical examination findings and laboratory tests in patients with and without hematological involvement. RESULTS: A total of 212 patients (127 boys (59.9%)) with a mean age of 9.4±4.7 years were evaluated in this study. Blood cultures were performed in 161 (75.9%) patients and Brucella spp were isolated in 70 (43.4%) of them. Ninety-two (43.4%) patients had hematological involvement at least in one series. Anemia was detected in 66 (31.7%) patients, leukopenia in 22 (10.6%) and thrombocytopenia in 10 (4.8%). Four patients (1.9%) had pancytopenia. Age distrubutions of the patients with and without hematological involvement were similar (p=0.6). In patients presented with fever, hepatomegaly and splenomegaly, hematologic involvement was significantly higher (p < 0.05). Hematological involvement was higher in patients who had elevated aspartate aminotransferase and alanine aminotransferase concentrations (p < 0.05). Hematological involvement was higher in patients with positive blood culture (p=0.005). Six patients (2.8%) were treated with intravenous immunoglobulin at 1000 mg/kg/day for two days in addition to anti-brucellosis treatment. CONCLUSIONS: Hematological involvement in brucellosis is a common finding regardless of age, especially in febrile, bacteremic patients and in patients who had hepatosplenomegaly and elevated liver enzymes. Anemia is the most common hematological abnormality.
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Anemia , Brucelosis , Leucopenia , Trombocitopenia , Adolescente , Anemia/epidemiología , Anemia/etiología , Brucelosis/complicaciones , Brucelosis/diagnóstico , Brucelosis/tratamiento farmacológico , Niño , Preescolar , Femenino , Fiebre , Hepatomegalia , Humanos , Leucopenia/diagnóstico , Leucopenia/epidemiología , Leucopenia/etiología , Masculino , Estudios Retrospectivos , Esplenomegalia , Centros de Atención Terciaria , Trombocitopenia/diagnóstico , Turquía/epidemiologíaRESUMEN
INTRODUCTION: Dengue is an infectious disease. This disease is prevalent mainly in the terai belts of Nepal. But in the last few years, the cases are in increasing trend in the hilly areas of Nepal. The aim of this study was to find out the prevalence of admitted dengue cases among adult dengue-positive cases in a tertiary care centre. METHODS: This was a descriptive cross-sectional study done at a tertiary teaching hospital after obtaining ethical approval from the Institutional Review Committee (Reference number: 063/2077/2078). Convenience sampling was used. The data of serologically confirmed dengue cases, during the period of 1 August 2019 to 1 December 2019, of ages above 15 years, were collected from the hospital records. Point estimate and 95% Confidence Interval were calculated. RESULTS: Out of 922 adult dengue-positive patients, 347 (37.63%) (36.04-39.22, 95% Confidence Interval) were admitted. Among them, 154 (44.38%) cases were seen during the month of September. A total of 264 (76.08%) were the inhabitants of the Kaski district. A total of one hundred seventy eight (51.29%) cases were males. The most common symptoms seen were fever among 335 (96.54%) patients and headache among 141 (40.63%) patients. Leukopenia was seen in 192 (55.33%) patients and thrombocytopenia was seen in 165 (47.55%) of the admitted cases. CONCLUSIONS: The prevalence of admitted dengue cases was higher as compared to other studies done in similar settings.
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Dengue , Leucopenia , Trombocitopenia , Masculino , Humanos , Adulto , Adolescente , Femenino , Estudios Transversales , Dengue/epidemiología , Dengue/diagnóstico , Centros de Atención Terciaria , Fiebre , Leucopenia/epidemiologíaRESUMEN
INTRODUCTION: Hematologic toxicity (HT), particularly leukopenia, is a common side-effect of oncologic treatments for pelvic malignancies. Pelvic nodal radiotherapy (PNRT) has been associated with HT development mainly through incidental bone marrow (BM) irradiation; however, several questions remain about the clinical impact of radiotherapy-related HT. Herein, we perform a systematic review of the available evidence on PNRT and HT. MATERIALS AND METHODS: A comprehensive systematic literature search was performed through EMBASE. Hand searching and clinicaltrials.gov were also used. RESULTS: While BM-related dose-volume parameters and BM-sparing techniques have been more thoroughly investigated in pelvic malignancies such as cervical, anal, and rectal cancers, the importance of BM as an organ-at-risk has received less attention in prostate cancer treatment. CONCLUSIONS: We examined the available evidence regarding the impact of PNRT on HT, with a focus on prostate cancer treatment. We suggest that BM should be regarded as an organ-at-risk for patients undergoing PNRT.
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Leucopenia , Linfopenia , Neoplasias de la Próstata , Radioterapia de Intensidad Modulada , Humanos , Leucopenia/epidemiología , Leucopenia/etiología , Masculino , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
INTRODUCTION: Thrombocytopenia and leucopenia are frequently encountered hematological disorders among people living with HIV/AIDS. This systematic review and meta-analysis were aimed to indicate the national prevalence of thrombocytopenia and leucopenia among HIV/AIDS patients. METHODS: This systematic review and meta-analysis was conducted following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. A systematic search was conducted from February 01, 2021 to April 02, 2021 using electronic databases Google Scholar, PubMed, Web of Sciences, Google, EMBASE, SCOPUS and ResearchGate. The quality of the included studies was assessed using Newcastle-Ottawa Quality Assessment Scale (NOS) adapted for cross-sectional studies. Data analysis was done using STATA version 14 using metan commands. Random effect meta-analysis was used to estimate the pooled prevalence of thrombocytopenia and leucopenia among people living with HIV/AIDS in Ethiopia. RESULT: Of the 349 initially searched articles, 90 were assessed for eligibility and only 13 articles published from 2014 to 2020 were included in the final meta-analysis. A total of 3854 participants were involved in the included studies. The pooled prevalence of thrombocytopenia was 9.69% (95%CI; 7.40-11.97%). Significant heterogeneity was observed with I2 value of 84.7%. Thrombocytopenia was 11.91% and 5.95% prevalent among HAART naive and HAART exposed HIV/AIDS patients, respectively. The pooled prevalence of leucopenia among HIV/AIDS patients was 17.31% (95%CI: 12.37-22.25%). CONCLUSION: This study showed a high prevalence of thrombocytopenia and leucopenia among people living with HIV/AIDS, indicating the necessity of regular screening of HIV seropositive patients for different hematological parameters and providing treatment.
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Síndrome de Inmunodeficiencia Adquirida/patología , Infecciones por VIH/patología , Leucopenia/epidemiología , Trombocitopenia/epidemiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Terapia Antirretroviral Altamente Activa , Bases de Datos Factuales , Etiopía/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Leucopenia/complicaciones , Leucopenia/diagnóstico , Trombocitopenia/complicaciones , Trombocitopenia/diagnósticoRESUMEN
BACKGROUND: Polymorphisms in thiopurine methyltransferase (TPMT) and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine induced leukopenia in the Western countries and East Asia respectively. Exact role of these polymorphisms in South Asian population with inflammatory bowel disease (IBD) is uncertain. METHODS: We included consecutive patients with IBD who were initiated on thiopurines at a center in North India. The dosage of thiopurines was titrated using regular monitoring of hemogram and liver function tests. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) and one NUDT15 polymorphism (c.415 C > T) were assessed. Comparison regarding incidence of leukopenia and maximum tolerated thiopurine dosage was performed between those with wild polymorphism and those with TPMT and NUDT15 polymorphisms, respectively. RESULTS: Of the 119 patients (61 males, mean age 36.8 ± 13.5 years), 105 (88.2%) had ulcerative colitis and 14 (11.8%) had Crohn's disease. Leukopenia was noted in 33 (27.7%), gastrointestinal intolerance in 5 (4.2%) and pancreatitis in 2 (1.6%). TPMT polymorphisms were detected amongst five patients of whom 1 developed leukopenia. NUDT15 polymorphism was noted in 13 patients of whom 7 had leukopenia. The odds of developing leukopenia in TPMT polymorphism were non-significant (0.77, 95% CI:0.0822 to 7.2134, P = 0.819) but were significantly higher in those with NUDT15 polymorphism (3.5933, 1.1041 to 11.6951, P value: = 0.0336). CONCLUSION: NUDT15 polymorphism was more frequent than TPMT polymorphisms and was associated with thiopurine induced leukopenia. However, the tested polymorphisms account for only 24.2% of the risk of thiopurine induced leukopenia.
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Enfermedades Inflamatorias del Intestino , Leucopenia , Metiltransferasas/genética , Pirofosfatasas/genética , Adulto , Humanos , India/epidemiología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/genética , Leucopenia/inducido químicamente , Leucopenia/epidemiología , Leucopenia/genética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Dengue remains a major problem in the tropics. Several Asian countries have reported an increasing trend in the proportion of infants with dengue fever. However, most studies are limited to case reports or small case series from isolated outbreaks. We planned this study to look at clinico-laboratory profile, outcome, and predictors of severity in a large cohort of infants over a decade. Electronic medical records of infants admitted at a tertiary center of South India, with laboratory confirmed dengue infection between 2009 and 2019 were reviewed. Diagnosis was based on detection of NS-1 antigen and/or immunoglobulin M antibody against DENV(dengue virus) or positive DENV RNA polymerase chain reaction in infants presenting with acute febrile illness and clinical features consistent with dengue. Of 395 children with dengue admitted during study period, 99 (25%) were infants. A cyclical incidence pattern was noted, with higher cases in alternate years. Fever (99%) was most common, followed by gastrointestinal symptoms (vomiting, diarrhea-28%) and upper respiratory symptoms (cough, coryza-22%). Fifty-three infants had severe dengue, and 39 had shock. Fourteen children had multiorgan dysfunction syndrome, and 13 died. Infants with severe dengue were older than those with nonsevere disease, had lower serum albumin and greater frequency of severe thrombocytopenia, and had coagulopathy. On multivariable analysis, low serum albumin predicted development of severe dengue [P = 0.003, odds ratio 12.4 (95% confidence interval: 2.42-63.7)]. Dengue in infants may be challenging to recognize because of its undifferentiated presentation, with gastrointestinal and upper respiratory symptoms that are similar to other viral illness. Severe dengue is common in this sample, and lower serum albumin at presentation was predictive of severe disease.
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Virus del Dengue , Dengue , Anticuerpos Antivirales/sangre , Asia/epidemiología , Estudios de Cohortes , Dengue/diagnóstico , Dengue/epidemiología , Dengue/patología , Virus del Dengue/aislamiento & purificación , Femenino , Fiebre/epidemiología , Humanos , Inmunoglobulina M/sangre , Incidencia , India/epidemiología , Lactante , Leucopenia/epidemiología , Masculino , Patología Molecular , Reacción en Cadena de la Polimerasa , Prevalencia , Estudios Retrospectivos , Pruebas Serológicas , Dengue Grave/epidemiología , Trombocitopenia/epidemiologíaRESUMEN
OBJECTIVES: There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX. METHODS: This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat. RESULTS: 178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen. CONCLUSION: A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially. TRIAL REGISTRATION NUMBER: CTRI/2018/12/016549.
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Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/administración & dosificación , Adolescente , Adulto , Artritis Reumatoide/fisiopatología , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/epidemiología , Humanos , Leucopenia/inducido químicamente , Leucopenia/epidemiología , Masculino , Metotrexato/análogos & derivados , Metotrexato/sangre , Persona de Mediana Edad , Ácido Poliglutámico/análogos & derivados , Ácido Poliglutámico/sangre , Trombocitopenia/inducido químicamente , Trombocitopenia/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Surgical resection is the primary treatment for HCC; however, it is associated with a high rate of recurrence and death. We conducted this phase 2 study to investigate the efficacy and safety of postoperative intensity-modulated radiotherapy (IMRT) for HCC after narrow-margin hepatectomy. APPROACH AND RESULTS: We designed a single-arm, prospective phase 2 trial to evaluate overall survival (OS), disease-free survival (DFS), recurrence patterns, and toxicity in patients receiving adjuvant radiotherapy. The eligibility criteria included the following: pathological diagnosis of HCC after hepatectomy, with narrow pathological margins (< 1 cm); age > 18 years; and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received IMRT within 4-6 weeks after surgical resection. This trial was registered at ClinicalTrials.gov (NCT01456156). Between 2008 and 2016, a total of 76 eligible patients who underwent narrow-margin resection were enrolled. The median follow-up duration was 70 months; the 3-year OS and DFS rates were 88.2% and 68.1%, respectively; and the 5-year OS and DFS rates were 72.2% and 51.6%, respectively. Intrahepatic recurrence was the primary recurrence pattern. No marginal recurrence was found. Intrahepatic, extrahepatic, and combined recurrences at the first relapse were found in 33, 5, and 1 patient, respectively. The most common radiation-related grade-3 toxicities were leukopenia (7.9%), elevated alanine aminotransferase (3.9%) and aspartate aminotransferase (2.6%) levels, and thrombocytopenia (1.3%). Classical or nonclassical radiation-induced liver disease was not noted. CONCLUSIONS: Adjuvant radiotherapy is an effective, well-tolerated, and promising adjuvant regimen in patients with HCC who have undergone narrow-margin hepatectomy. Our trial provides evidence and a rationale for planning a future phase 3 trial.
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Carcinoma Hepatocelular/terapia , Hepatectomía/métodos , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia/epidemiología , Radioterapia de Intensidad Modulada/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucopenia/epidemiología , Leucopenia/etiología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/métodos , Radioterapia de Intensidad Modulada/métodos , Trombocitopenia/epidemiología , Trombocitopenia/etiologíaRESUMEN
BACKGROUND: Although both leukocytosis and leukopenia have been considered Systemic Inflammatory Response Syndrome criteria, leukopenia is not generally considered a normal response to infection. We sought to evaluate the prognostic validity of leukopenia as a sign of sepsis-defining hematological organ dysfunction within the Sepsis-3 framework. We hypothesized that leukopenia is associated with higher risk of mortality than leukocytosis among patients with suspected infection. METHODS: We performed a retrospective cohort study using the Medical Information Mart v1.4 in Intensive Care-III database. Multivariable regression models were used to evaluate the association between leukopenia and mortality in patients with suspected infection defined by Sepsis-3. RESULTS: We identified 5,909 ICU patients with suspected infection; 250 (4.2%) had leukopenia. Leukopenia was associated with increased in-hospital mortality compared with leukocytosis (OR, 1.5; 95% CI 1.1-1.9). After adjusting for demographics and comorbidities in the Sepsis-3 consensus model, leukopenia remained associated with increased risk of mortality compared with leukocytosis (OR 1.6, 95% CI 1.2-2.2). Further adjustment for the platelet component of the SOFA attenuated the association between leukopenia and mortality (OR decreased from 1.5 to 1.1). However, 83 (1.4%) of patients had leukopenia without thrombocytopenia and 14 had leukopenia prior to thrombocytopenia. CONCLUSIONS: Among ICU patients with suspected infection, leukopenia was associated with increased risk of death compared with leukocytosis. Due to correlation with thrombocytopenia, leukopenia did not independently improve the prognostic validity of SOFA; however, leukopenia may present as a sign of sepsis prior to thrombocytopenia in a small subset of patients.
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Biomarcadores/análisis , Mortalidad Hospitalaria/tendencias , Leucopenia/epidemiología , Insuficiencia Multiorgánica/diagnóstico , Puntuaciones en la Disfunción de Órganos , Sepsis/complicaciones , Anciano , Femenino , Estudios de Seguimiento , Humanos , Unidades de Cuidados Intensivos , Masculino , Massachusetts/epidemiología , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Leukopenia occurs frequently following kidney transplantation and is associated with adverse clinical outcomes including increased infectious risk. In this study we sought to characterize the causes and complications of leukopenia following kidney transplantation. METHODS: In a cohort of adult patients (≥18 years) who underwent kidney transplant from Jan 2006-Dec 2017, we used univariable Cox proportional Hazards models to identify predictors of post-transplant leukopenia (WBC < 3500 mm3). Factors associated with post-transplant leukopenia were then included in a multivariable backwards stepwise selection process to create a prediction model for the outcome of interest. Cox regression analyses were subsequently used to determine if post-transplant leukopenia was associated with complications. RESULTS: Of 388 recipients, 152 (39%) developed posttransplant leukopenia. Factors associated with leukopenia included antithymocyte globulin as induction therapy (HR 3.32, 95% CI 2.25-4.91), valganciclovir (HR 1.84, 95% CI 1.25-2.70), tacrolimus (HR 3.05, 95% CI 1.08-8.55), prior blood transfusion (HR 1.17 per unit, 95% CI 1.09- 1.25), and donor age (HR 1.02 per year, 95% CI 1.00-1.03). Cytomegalovirus infection occurred in 26 patients with leukopenia (17.1%). Other than cytomegalovirus, leukopenia was not associated with posttransplant complications. CONCLUSION: Leukopenia commonly occurred posttransplant and was associated with modifiable and non-modifiable pretransplant factors.