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1.
Yale J Biol Med ; 97(3): 325-333, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39351319

RESUMEN

Brain abscess is life-threatening and carries a high risk of mortality. Despite advances in sensitive imaging techniques, effective antimicrobial therapies, and sophisticated surgical procedures, diagnosing and treating brain abscesses remains challenging. Although empirical antimicrobial therapy and neurosurgery are considered primary treatments for brain abscesses, their efficacy is limited by potential side effects including neutropenia development, the need for repeat surgeries, and the risk of new-onset epilepsy. Here, we present a case of a 52-year-old male patient who experienced paroxysmal convulsions accompanied by left-sided limb weakness and numbness for over 2 months. Despite a brain MRI revealing a multilocular cystic lesion in the right frontal lobe, with about 28 mm × 19 mm × 21 mm in size, the patient declined neurosurgical interventions. After completing a 6-week course of antimicrobial therapy, the patient sought traditional Chinese medicine (TCM) treatment. As a result, the patient remained free of paroxysmal convulsions for about 60 days after a 4-month TCM treatment. A follow-up MRI imaging at 8 months showed a reduction in the size of the lesion in the right frontal lobe to 8 mm × 4 mm. To the best of our knowledge, this is the first well-documented case of a brain abscess that was successfully managed with a combination of antimicrobial therapy and TCM. This case report suggests that TCM may provide significant supplementary benefits in managing infections like brain abscesses. However, further evidence from prospective studies is necessary to substantiate the efficacy of Chinese herbal medicine for the treatment of brain abscesses.


Asunto(s)
Absceso Encefálico , Imagen por Resonancia Magnética , Medicina Tradicional China , Humanos , Absceso Encefálico/tratamiento farmacológico , Absceso Encefálico/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Medicina Tradicional China/métodos , Resultado del Tratamiento , Antibacterianos/uso terapéutico
2.
Support Care Cancer ; 32(11): 715, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39377915

RESUMEN

BACKGROUND: Using granulocyte colony-stimulating factor (G-CSF) after completing chemotherapy reduces the duration of neutropenia and infections. However, the efficacy and safety of prophylactic pegfilgrastim in acute lymphoblastic leukemia (ALL) patients have not yet been evaluated after intensive cytotoxic chemotherapy compared to the daily G-CSF. This study aimed to evaluate the efficacy of pegfilgrastim for ALL patients who received intensive chemotherapy compared with a short-acting G-CSF. PATIENTS AND METHODS: Clinical data of 145 patients treated with hyper-CVAD, modified VPDL/VPD, or KALLA 1406/1407 regimen were retrospectively evaluated. Pegfilgrastim or the short-acting G-CSF was selected according to the clinician's discretion. Patients not receiving pegfilgrastim were treated with the short-acting G-CSF. RESULTS: The median age of enrolled patients was 45 years. Sixty newly diagnosed ALL patients were treated with hyper-CVAD regimen, while KALLA and VPDL regimens were administered to 39 and 46 patients, respectively. Among the 60 patients treated with hyper-CVAD, 20 patients received pegfilgrastim. Patients who received pegfilgrastim had a significantly shorter duration of neutropenia and hospitalization and reduced incidence of severe infections compared to patients receiving the short-acting G-CSF. Consistent results were also confirmed in an analysis targeting only patients who achieved remission during hyper-CVAD induction therapy. There was no significant difference in neutrophil recovery ability and hospitalization duration when the daily short-acting G-CSF was used prophylactically after completing hyper-CVAD, KALLA, and VPDL regimens as induction therapy. CONCLUSION: Using pegfilgrastim after hyper-CVAD therapy was more effective than the short-acting G-CSF in terms of infection, neutropenia recovery, and hospitalization in patients with newly diagnosed ALL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Filgrastim , Factor Estimulante de Colonias de Granulocitos , Neutropenia , Polietilenglicoles , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteínas Recombinantes , Humanos , Filgrastim/administración & dosificación , Filgrastim/uso terapéutico , Polietilenglicoles/administración & dosificación , Masculino , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Adolescente , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Anciano , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico
3.
Am J Med Genet A ; : e63901, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39392177

RESUMEN

Mosaic variegated aneuploidy (MVA) is an autosomal recessive disorder characterized by mosaic aneuploidies, predominantly trisomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies, and most patients present with intrauterine growth delay, microcephaly, and a broad spectrum of congenital abnormalities. We report a patient with a distinctive type of MVA discovered in bone marrow (BM) when she was 3-month-old due to neutropenia and hypocellular bone marrow. She was followed up for more than 20 years, and different trisomic cells were repeatedly discovered in different tissues, whereas her clinical picture has never been severe. The main sign remained intermittent neutropenia, not cyclic and often not too severe, occasionally with anemia and thrombocytopenia. Retromicrognathia was the only dysmorphic sign. Unlike other patients with MVA, the trisomies in all tissues involved almost invariably chromosomes 18 and 19. Therefore, the peculiarities of our patient were the clinical and the atypical cytogenetic pictures. Nevertheless, we looked for mutations in the seven causative genes of the known types of MVA, but the results were negative. Then, we analyzed the entire exome to find out other possible causing mutations, but also this attempt failed to discover a possible cause of this distinctive form of MVA.

4.
Sci Rep ; 14(1): 23309, 2024 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-39375403

RESUMEN

Breast cancer remains a significant public health issue, often resulting in severe side effects such as neutropenia, highlighting the need for reliable predictors of clinical outcomes. This study aimed to evaluate the predictive value of body composition measures for mortality, recurrence, and chemotherapy-induced neutropenia in patients with breast cancer following surgery and chemotherapy. We retrospectively analyzed 85 breast cancer patients who underwent surgery and chemotherapy between 2006 and 2016. Body composition was assessed using computed tomography (CT) or positron emission tomography (PET) at diagnosis and three years and five years post-diagnosis. Metrics included skeletal muscle area (SMA), skeletal muscle index (SMI), subcutaneous adipose tissue area (SAT), and visceral adipose tissue area (VAT). Longitudinal analysis revealed a decrease in muscle mass (P < 0.001 for both SMA and SMI) and nonsignificant changes in fat mass (P = 0.449 for SAT and P = 0.798 for VAT). A lower SMI at diagnosis was significantly associated with increased mortality (P = 0.019) and a higher incidence of grade 4 neutropenia (P = 0.008). There was no significant association between SMI at diagnosis and recurrence (P = 0.691). No associations were found between body composition measurements during the follow-up period and the clinical outcomes. Lower skeletal muscle mass at diagnosis is strongly associated with higher mortality and chemotherapy-induced complications in patients with breast cancer, highlighting the potential of readily available imaging techniques as valuable predictors of clinical outcomes.


Asunto(s)
Composición Corporal , Neoplasias de la Mama , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Anciano , Adulto , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Músculo Esquelético/efectos de los fármacos , Tomografía Computarizada por Rayos X , Neutropenia/inducido químicamente , Grasa Intraabdominal/diagnóstico por imagen , Tomografía de Emisión de Positrones , Recurrencia Local de Neoplasia , Grasa Subcutánea/diagnóstico por imagen , Grasa Subcutánea/patología
5.
Virus Res ; 350: 199479, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39374843

RESUMEN

Human Pegivirus-1, typically regarded as a commensal virus, exhibits high prevalence in humans. Its frequency and impact on oncologic pediatric patients with febrile neutropenia (FN), a frequent chemotherapy complication, remains unexplored. In this study, we assessed HPgV-1 RNA prevalence in pediatric patients experiencing FN. Blood samples were collected from 30 children, 15 presenting FN and 15 comprising a control group of either undergoing treatment or in remission. Overall, HPgV-1 RNA was detected in 23.3 % of samples (26.7 % among FN patients and 20.0 % among those under treatment or in remission). Phylogenetic analysis unveiled HPgV-1 genotype 2 predominance among these samples, the most prevalent strain circulating in Brazil. Our findings prompt crucial inquiries into the role of HPgV-1 RNA in FN: is it an incidental finding and if it can influences this clinical entity? Further investigation is imperative to elucidate HPgV-1 implications in vulnerable patients cohorts, potentially informing new approaches and understanding viral dynamics in immunocompromised populations.

6.
Auris Nasus Larynx ; 51(6): 971-975, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39395388

RESUMEN

OBJECTIVE: Febrile neutropenia (FN) is the most serious toxicity in patients with head and neck squamous cell carcinoma (HNSCC) treated with induction chemotherapy (IC). Although it is well-known that sarcopenia is a risk factor for severe toxicity of (chemo)radiotherapy, the data on the association between sarcopenia and FN during IC in HNSCC patients is rare. This study determined the impact of sarcopenia on FN during IC. METHODS: IC-treated patients with HNSCC were enrolled in this study. Skeletal muscle mass (SMM) at the C3 vertebral body was used to define sarcopenia from computed tomography (CT) scans. To determine the predictive effect of low SMM on FN, logistic regression analysis was performed. RESULTS: In this study, 71 patients were included, of whom 28 had low SMM and 14 experienced FN. In multivariate analysis, low SMM and high CRP were the independent predictive factors for FN. The combination index of sarcopenia and CRP showed a greater odds ratio than sarcopenia alone suggesting a more significant predicting indicator. CONCLUSIONS: Sarcopenia defined by CT imaging is associated with FN in patients with HNSCC treated with IC. The combination of sarcopenia and high CRP is a more significant risk factor, and it helps determine patients at risk of FN during IC.

7.
Clin Infect Dis ; 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39397538

RESUMEN

Although occult fungal, viral and multidrug-resistant bacterial infections can cause persistent fever in neutropenic patients with hematologic cancer, a variety of non-infectious entities should be considered in case-by-case basis in the context of negative diagnostic workup for infection.

8.
Porto Biomed J ; 9(5): 266, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39403703

RESUMEN

Acute myeloid leukemia (AML) treated with intensive chemotherapy carries a high risk of severe infection. The development of reliable assessment tools to promptly identify patients at risk of developing critical illness is essential to prevent delays in intensive care unit (ICU) admission. This study evaluated the accuracy of quick Sequential Organ Failure Assessment (qSOFA) score, National Early Warning Score (NEWS), and NEWS2 score in predicting ICU admission and sepsis-related mortality in this population. A retrospective analysis was conducted, including 365 episodes of febrile neutropenia in 126 patients. The results showed that all three scores-qSOFA, NEWS, and NEWS2-demonstrated good accuracy for all outcomes, with area under the receiver-operating characteristic curve values for sepsis-related mortality of 0.812, 0.858, and 0.848, respectively. In addition, the scores exhibited excellent accuracy in predicting ICU admission and the composite outcome of ICU admission or sepsis-related mortality. To our knowledge, this is the first study to evaluate the accuracy of NEWS in a population of patients with AML who did not undergo stem cell transplantation. These findings suggest that NEWS and NEWS2 are effective tools for identifying patients with AML at high risk of clinical deterioration during febrile neutropenia, supporting their use in clinical practice.

9.
J Infect Chemother ; 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39396607

RESUMEN

BACKGROUND AND OBJECTIVE: Inappropriate initial antimicrobial therapy has been associated with high mortality in patients with gram-negative bacilli bloodstream infections during febrile neutropenia following chemotherapy for hematological malignancies. The aim of this study is to determine this association in our hospital. METHODS: A single center, retrospective, cohort study of bloodstream infection due to gram-negative bacilli and febrile neutropenia was conducted. Clinical characteristics, microbiological etiology, antimicrobial resistance profile, empirical and targeted antibiotic therapy, intensive care unit admission, persistent bacteremia and mortality were analyzed. RESULTS: Of the 171 episodes of bloodstream infection due to gram-negative bacilli, empirical antimicrobial therapy was inappropriate in 43 episodes (25.1%). There was a significant difference in mortality at 7 and 30 days between patients who received appropriate versus inappropriate empirical treatment (4.6% versus 13.9%, p= 0.04; 15.6% versus 32.5%, p= 0.016). Inappropriate empirical treatment (RR, 2.97 [95% CI, 1.01 - 8.74]), shock at the time of febrile neutropenia diagnosis (RR, 6.5 [95% CI, 1.83 - 23.05]) carbapenem-resistant microorganism (RR, 3.73 [95% CI, 1.14 - 12.24]) and persistent bacteremia (RR, 84.6 [95% CI, 11.3 - 629.4]) were associated with an increased mortality at 7 and 30 days. In the multivariate analysis, shock (RR, 4.85 [95% CI, 2.10 - 11.65]) and persistent bacteremia was independently associated with increased 30-day mortality, but inappropriate empirical antimicrobial therapy was not an independent prognostic determinant (RR, 1.66 [0.53 - 4.82]). CONCLUSION: Shock at the time of febrile neutropenia diagnosis contributes to mortality in patients with gram-negative bacilli bloodstream infection, in this scenario, appropriate empirical antimicrobial therapy should be encouraged.

10.
Front Cardiovasc Med ; 11: 1465912, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39309604

RESUMEN

Barth syndrome (BTHS) is a rare X-linked recessive genetic disorder characterized by a broad spectrum of clinical features including cardiomyopathy, skeletal myopathy, neutropenia, growth delay, and 3-methylglutaconic aciduria. This disease is caused by loss-of-function mutations in the TAFAZZIN gene located on chromosome Xq28, resulting in cardiolipin deficiency. Most patients are diagnosed in childhood, and the mortality rate is highest in the early years. We report a case of acute, life-threatening metabolic decompensation occurring one day after birth. A novel TAFAZZIN splice site mutation was identified in the patient, marking the first reported case of such a mutation in BTHS identified in China. The report aims to expand our understanding of the spectrum of TAFAZZIN mutations in BTHS.

11.
Sci Rep ; 14(1): 21891, 2024 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300133

RESUMEN

Chronic idiopathic neutropenia (CIN) is a rare benign condition  caused by an immune attack against neutrophils, either primary or in the context of other autoimmune conditions, lymphoproliferative syndromes, and inborn errors of immunity. In this single-center prospective study, 131 adult CIN patients were enrolled (median age 55 years, range: 20-93). At baseline, 56% had anti-neutrophil autoantibodies and 31% had autoimmune comorbidities. Over a median 3-year follow-up, the rate of grade ≥ 2 infections was 42%, with 10% grade ≥ 3, irrespective of neutrophil counts, demographics, and anti-neutrophil antibodies positivity, and G-CSF was used in 6 patients only. No malignant evolution nor deaths were observed. Bone marrow evaluation showed a large granular lymphocyte (LGL) infiltrate in 52%, mostly polyclonal, and hypocellularity in 31% of cases. Immune-histochemistry highlighted deposits of IgG, IgM, and complement fractions C3 and C4d in most cases. Interestingly, 19% of tested patients displayed somatic mutations of myeloid genes with an association with age. In conclusion, adult CIN appears to be a benign condition without life-threatening infections, yet deserving an extensive hematologic evaluation including bone marrow assessment to inform the differential diagnosis.


Asunto(s)
Neutropenia , Humanos , Adulto , Persona de Mediana Edad , Masculino , Femenino , Neutropenia/inmunología , Anciano , Anciano de 80 o más Años , Estudios Prospectivos , Adulto Joven , Neutrófilos/inmunología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Médula Ósea/patología
12.
Antibiotics (Basel) ; 13(9)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39334996

RESUMEN

INTRODUCTION: Febrile neutropenia (FN) is a potentially severe entity, particularly in hemato-oncologic patients who have higher incidence of colonization with multidrug-resistant bacteria. Discrepancies among guidelines contribute to divergence in antimicrobial practices. Our objective was to assess the variation of practices in antimicrobial therapy in high-risk FN among Portuguese hematologists. METHODS: We conducted a cross-sectional study through the implementation of an online survey, open to all clinical hematologists in the country. To characterize practice patterns regarding critical elements in FN management, three clinical vignettes were designed to describe typical situations where narrow-spectrum empiric antibiotics (vignette 1), short-course therapy (vignette 2) and de-escalation (vignette 3) could be performed. The remaining questions characterized clinical experience, department size, and differentiation and decision-making process regarding FN antibiotic therapy. RESULTS: The survey yielded 31 responses from 11 hospitals across four regions. All respondents opted for empiric narrow-spectrum antibiotics, 22.6% opted for short-course therapy (mostly senior specialists from larger settings) and 35.5% for de-escalation (mostly young specialists). Availability of an FN protocol seemed to favor both approaches. These findings should be complemented by qualitative assessments of barriers to best practices and should support the need for interventions to improve antibiotic use in febrile neutropenia.

13.
ACS Biomater Sci Eng ; 10(10): 6661-6676, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39269431

RESUMEN

Poly(lactide-co-glycolide) (PLGA) is a biocompatible and biodegradable copolymer that has gained high acceptance in biomedical applications. In the present study, PLGA (Mw = 13,900) was synthesized by ring-opening polymerization in the presence of a biocompatible zinc-proline initiator through a green route. Irinotecan (Ir) loaded with efficient PLGA core-lipid shell hybrid nanocarriers (lipomers, LPs) were formulated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000] (DSPE-PEG-2000), using soya lecithin, by a nanoprecipitation method, and the fabricated LPs were designated as P-DSPE-Ir and P-DSPE-PEG-Ir, respectively. The formulated LPs were further validated for their physicochemical properties and biological potential for colon cancer application. The potential delivery of a poorly water-soluble chemotherapeutic drug (Ir) was studied for the treatment of colon cancer. LPs were successfully prepared, providing controlled size (80-120 nm) and surface charge (∼ -35 mV), and the sustained release properties and cytotoxicity against CT-26 colon cancer cells were studied. The in vivo biodistribution and tumor site retention in CT-26 xenograft tumor-bearing Balb/C mice showed promising results for tumor uptake and retention for a prolonged time period. Unlike P-DSPE-Ir, the P-DSPE-PEG-Ir LP exhibited significant tumor growth delay as compared to untreated and blank formulation-treated groups in CT-26 (subcutaneous tumor model) after 4 treatments of 10 mg irinotecan/kg dose. The biocompatibility and safety of the LPs were confirmed by an acute toxicity study of the optimized formulation. Overall, this proof-of-concept study demonstrates that the PLGA-based LPs improve the efficacy and bioavailability and decrease neutropenia of Ir to combat colon cancer.


Asunto(s)
Neoplasias del Colon , Portadores de Fármacos , Irinotecán , Polietilenglicoles , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Animales , Irinotecán/uso terapéutico , Irinotecán/farmacología , Irinotecán/farmacocinética , Irinotecán/química , Irinotecán/administración & dosificación , Portadores de Fármacos/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Humanos , Polietilenglicoles/química , Línea Celular Tumoral , Ratones , Nanopartículas/química , Nanopartículas/uso terapéutico , Fosfatidiletanolaminas/química , Ratones Endogámicos BALB C , Camptotecina/uso terapéutico , Camptotecina/farmacología , Camptotecina/química , Camptotecina/farmacocinética , Camptotecina/análogos & derivados , Camptotecina/administración & dosificación , Lípidos/química , Femenino
14.
Mycopathologia ; 189(5): 84, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39283560

RESUMEN

BACKGROUND: Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. METHODS: An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. RESULTS: 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. CONCLUSION: Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management.


Asunto(s)
Fluorodesoxiglucosa F18 , Infecciones Fúngicas Invasoras , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/diagnóstico por imagen , Infecciones Fúngicas Invasoras/diagnóstico , Encuestas y Cuestionarios , Huésped Inmunocomprometido , España , Italia
15.
BMC Neurol ; 24(1): 353, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300408

RESUMEN

BACKGROUND: Reversible splenial lesion syndrome (RESLES) is known as a neuro-imaging syndrome with recurrent but reversible lesion of the corpus callosum, characterized by nonspecific but usually mild encephalopathies and specific imaging manifestations.There are few published reports in the field of oncology. CASE PRESENTATION: A 33-year-old female with right breast cancer and with no particular family history was admitted to hospital with high fever and severe headache, after receiving adjuvant radiotherapy. Blood routine test upon admission suggested neutropenia, considering myelosuppression associated with radiotherapy. There were no definite findings of common pathogenic microorganism, and no imaging indication of certain infectious sites other than a likely reversible corpus callosum syndrome suggested by brain MRI, which was relieved after systemic antibiotic therapy and granulocyte colony-stimulating factor injection. CONCLUSIONS: Reversible splenial lesion syndrome is a kind of clinical-imaging syndrome with multiple clinical manifestations and etiologies. This breast cancer patient after postoperative adjuvant radiotherapy develops a complication of RESLES that rings an alarm bell to the oncologists not to easily recognize the corpus callosum lesion as infarction or metastasis. Meanwhile, the potential pathogenic mechanisms need to be explored further.


Asunto(s)
Neoplasias de la Mama , Cuerpo Calloso , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/complicaciones , Adulto , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Radioterapia Adyuvante/efectos adversos , Neutropenia Febril/etiología , Imagen por Resonancia Magnética
16.
Front Immunol ; 15: 1373495, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39286252

RESUMEN

Background: Homozygous or compound heterozygous mutations in JAGN1 cause severe congenital neutropenia. JAGN1-mutant patients present with severe early-onset bacterial infections and most have been described as low-responders to recombinant granulocyte colony-stimulating factor (G-CSF) therapy. In a murine, hematopoietic JAGN1 knockout model, which displays susceptibility to Candida albicans infection in the absence of neutropenia, treatment with granulocyte-macrophage-CSF (GM-CSF) was able to restore the functional defect of neutrophils. Patients: We present two unrelated patients with biallelic JAGN1 mutations, who were both treated with subcutaneous GM-CSF (sargramostim) after treatment failure to G-CSF. The first patient was an 18-year-old pregnant woman who received GM-CSF at 12 weeks of gestation up to a dose of 10 µg/kg/d for 7 days. The second patient was a 5-month-old girl who received GM-CSF for a total of 9 days at a dose of up to 20 µg/kg/d. GM-CSF did not increase neutrophil counts in our patients. Treatment was stopped when neutrophil numbers declined further, no beneficial effect was noticed, and patients presented with infections. No adverse effects were observed in either patient and the fetus. Both patients ultimately underwent successful hematopoietic stem cell transplantation. Discussion: Both patients showed a high recurrence rate of severe infections on G-CSF treatment. GM-CSF therapy did not ameliorate the clinical phenotype, in contrast to the improvement of neutrophil function observed in the JAGN1 mouse model. No major additional extra-hematopoietic manifestations were evident in our patients. Conclusion: In two unrelated patients, GM-CSF did not have any beneficial effect on neutrophil counts. Patients with JAGN1-mutant SCN with reduced G-CSF responsiveness and elevated infection rate should be evaluated early for stem cell transplantation.


Asunto(s)
Síndromes Congénitos de Insuficiencia de la Médula Ósea , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Mutación , Neutropenia , Neutrófilos , Proteínas Recombinantes , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Humanos , Femenino , Neutropenia/congénito , Neutropenia/tratamiento farmacológico , Neutropenia/genética , Neutrófilos/inmunología , Adolescente , Síndromes Congénitos de Insuficiencia de la Médula Ósea/genética , Lactante , Proteínas Recombinantes/uso terapéutico , Fenotipo , Embarazo , Proteínas de la Membrana
17.
Vet Comp Oncol ; 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39305174

RESUMEN

Vincristine sulphate, a microtubule inhibitor, is used extensively in veterinary oncology for treating lymphoma. Neutropenia during multiagent protocols is a common reason for treatment delay and reduced dose intensity. This study evaluated toxicities associated with treating systemically well neutropenic lymphoma patients with vincristine. Lymphoma patients undergoing CHOP were evaluated retrospectively for instances of vincristine administration when absolute neutrophil counts (ANC) were 1.5 × 109/L or below. Instances of vincristine administration when ANC was equal to or less than 1.5 × 109/L were compared to vincristine administration where ANC was greater than 1.5 × 109/L in the same patient. Univariate and multivariate modelling compared VCOG-CTCAE v1.1 grading of vomiting, diarrhoea, anorexia and 7-day neutrophil nadir between groups. The median dose of vincristine administered was 0.7 mg/m2 for both study groups. A total of 112 doses of vincristine were administered to neutropenic patients (grade 2 n: 76, grade 3 n: 26, and grade 4 n: 10). These were compared to 223 doses of vincristine administered to the same patients when ANC was above 1.5 × 109/L. Neutropenic administration was most prevalent 7 days following cyclophosphamide administration. Day 7 post-administration neutropenia was more prevalent in patients with ANC greater than 1.5 × 109/L at the time of vincristine administration (neutropenic 9%; non-neutropenic 18%). Relative risk of 7-day neutropenia, vomiting, diarrhoea, and anorexia was similar between groups on multivariate analysis. Patients with lymphoma who receive vincristine when ANC is 1.5 × 109/L or below are at no greater risk of adverse effects than the same patient who receives vincristine when neutrophil counts are greater than 1.5 × 109/L.

18.
Clin Med Insights Oncol ; 18: 11795549241281330, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39323980

RESUMEN

Background: Febrile neutropenia (FN) poses a significant challenge in cancer treatment, with a high incidence among patients undergoing standard therapies. Predicting FN complications and outcomes remains crucial for improving patient management strategies. Biomarkers, including procalcitonin and albumin, have garnered attention for their potential prognostic value in FN. Methods: We conducted a prospective observational study at a tertiary hospital, enrolling 185 adult cancer patients experiencing FN episodes. We assessed serum albumin levels and incorporated them into the Multinational Association for Supportive Care in Cancer (MASCC) risk index to enhance risk stratification. Results: Serum albumin levels displayed promising prognostic utility in febrile neutropenia (FN). They exhibited moderate specificity and sensitivity in predicting mortality during FN and 28-day mortality. Serum albumin levels were significantly associated with gastrointestinal infections, serving as an independent predictor. Integrating serum albumin into the MASCC risk index improved predictive accuracy for FN mortality by 50%, 28-day mortality by 66.67%, and respiratory tract infections by 62.50%, enhancing in this way risk stratification for FN-related complications. Conclusion: Serum albumin emerges as a promising biomarker for prognostication in FN, complementing existing risk assessment frameworks. Its incorporation into the MASCC risk index enhances predictive capabilities, aiding clinicians in identifying high-risk patients promptly. While albumin shows potential in predicting mortality and complications, further research is warranted to optimize sensitivity and specificity, ensuring its clinical utility.

19.
Antibiotics (Basel) ; 13(9)2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39335006

RESUMEN

We investigated the influence of a local guideline on the quality of febrile neutropenia (FN) management and the applicability of a computerized decision support system (CDSS) using real-life data. The study included 227 FN patients between April 2016 and January 2019. The primary outcome measure was the achievement of a 20% increase in the rate of appropriate empirical treatment of FN in bacteremic patients. The compatibility of the CDSS (the development of which was completed in November 2021) with local protocols was tested using standard patient scenarios and empirical antibiotic recommendations for bacteremic FN patients. In total, 91 patients were evaluated before (P1: between April 2016 and May 2017) and 136 after (P2: between May 2017 and January 2019) the guideline's release (May 2017). The demographic characteristics were similar. Appropriate empirical antibacterial treatment was achieved in 58.3% of P1 and 88.1% of P2 patients (p = 0.006). The need for escalation of antibacterial treatment was significantly lower in P2 (49.5% vs. 35.3%; p = 0.03). In P2, the performance of the CDSS and consulting physicians was similar (CDSS 88.8% vs. physician 88.83%; p = 1) regarding appropriate empirical antibacterial treatment. The introduction of the local guideline improved the appropriateness of initial empirical treatment and reduced escalation rates in FN patients. The high rate of compliance of the CDSS with the local guideline-based decisions in P2 highlights the usefulness of the CDSS for these patients.

20.
Medicina (Kaunas) ; 60(9)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39336436

RESUMEN

Background and Objectives: Infections are the most common and potentially life-threatening complications of the treatment of children with acute lymphoblastic leukemia (ALL). The aim of this study was to determine epidemiological, clinical, and microbiological characteristics of infections in pediatric patients with ALL. Materials and Methods: Twenty-three children (16 males and 7 females, with a mean age of 5.9 years (range of 1.3 to 12.2 years)) with ALL, treated at the Division of Hematology, Oncology, and Clinical Genetics, Department of Pediatrics, Clinical Hospital Center Rijeka, Croatia, from 1 January 2015 to 31 December 2020, were included in the study. Results: One hundred and four infectious episodes (IEs) were reported (an average of 4.5 IE per patient). IEs were more frequent in the intensive phases of antileukemic treatment. Neutropenia was present in 48 IEs (46.2%) with a duration greater than 7 days in 28 IEs (58.3%). The respiratory tract was the most common infection site (48.1%). We documented 49 bacterial (47.1%), 4 viral (3.9%), 4 fungal (3.9%), and 10 mixed isolates (9.6%), while in 37 IEs (35.6%), a pathogen was not isolated. The most common causes of bacteremia were coagulase-positive staphylococci. The most frequent empirical therapy was third- and fourth-generation cephalosporins, followed by piperacillin/tazobactam. The modification of first-line antimicrobial therapy was performed in 56.9% of IEs. Granulocyte-colony stimulating factor was administered in 53.8% of IEs, and intravenous immunoglobulins were administered in 62.5% of IEs. One patient required admission to the intensive care unit. No infection-related mortality was reported. Conclusions: ALL patients have frequent IEs. Close monitoring, the identification of risk factors, the rapid empirical use of antibiotics in febrile neutropenia, and the timely modification of antimicrobial therapy play key roles in reducing infection-related morbidity and mortality in children with ALL.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Niño , Preescolar , Masculino , Lactante , Croacia/epidemiología , Antibacterianos/uso terapéutico , Infecciones/complicaciones , Estudios Retrospectivos
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