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Transplantation Proceedings Mar 2024Loss of microbiota diversity has been clearly associated with poor outcomes in the allogeneic hematopoietic stem cell transplantation setting. However, the choice of the... (Comparative Study)
Comparative Study Randomized Controlled Trial
Loss of microbiota diversity has been clearly associated with poor outcomes in the allogeneic hematopoietic stem cell transplantation setting. However, the choice of the optimal antibiotic prophylaxis during the pre-engraftment phase remains unclear. We designed a prospective randomized study to compare our standard-of-care neutropenia prophylaxis (ciprofloxacin) with rifaximin. We enrolled 38 consecutive adult patients who underwent allogeneic hematopoietic stem cell transplantation setting and were randomly assigned to receive ciprofloxacin (20 patients) or rifaximin (18 patients) at day -1. Pretransplant and transplant characteristics did not differ between groups. Cumulative incidence (CI) of acute graft-vs-host disease grade II to IV and moderate/severe chronic graft-vs-host disease was similar in both groups. With a median follow-up of 13.2 months (range, 6.8-30.2) in surviving patients, the 1-year CI of relapse was 20.8% in ciprofloxacin vs 17.8% in rifaximin (P = .616). Importantly, the 1-year CI of treatment-related mortality was significantly reduced in the ciprofloxacin group (10.2% vs 27.8%, P = .032), leading to higher 1-year overall survival (88.9% vs 74.6%, P = .038). In Cox-regression multivariate analysis, antibiotic prophylaxis remained the only predictor of overall survival, independently of donor type, disease risk index, and moderate/severe chronic graft-vs-host disease. Further studies are needed to assess the effects on microbiota diversity and confirm these outcomes.
Topics: Adult; Humans; Ciprofloxacin; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Neutropenia; Prospective Studies; Rifaximin
PubMed: 38368126
DOI: 10.1016/j.transproceed.2023.12.010 -
Medicine Feb 2024Single-center prospective cohort diagnostic accuracy study. Our study aimed to evaluate the accuracy and reproducibility of Thoracic Ultrasound (TUS) in detecting...
Single-center prospective cohort diagnostic accuracy study. Our study aimed to evaluate the accuracy and reproducibility of Thoracic Ultrasound (TUS) in detecting pulmonary pathology in immunosuppressed patients. We conducted a single-center prospective study. Consecutive patients with febrile neutropenia who underwent CT (Computerized Tomography) underwent TUS evaluation within 24h of CT. Both studies were performed by an expert who was blinded to the clinical information and results of the alternative imaging modalities. 34 patients met the inclusion criteria. The median age was 39.9 years (±17 standard deviation). TUS as a diagnostic test had a sensitivity of 92.9% and specificity of 83.3%, negative predictive value of 71.4%, and positive predictive value of 96.3%. Substantial between-method agreement was demonstrated with a kappa of 0.71 (P = .001) between the TUS and chest CT findings. We obtained a kappa of 1 (P = .001) for the final diagnosis of Pleural Effusion (PE). We concluded that TUS is a promising screening test for immunocompromised individuals. The results showed good diagnostic performance of TUS compared to CT for the detection of pulmonary findings highly suggestive of pathology with high accuracy and reproducibility.
Topics: Humans; Adult; Cohort Studies; Prospective Studies; Point-of-Care Systems; Reproducibility of Results; Ultrasonography; Tomography, X-Ray Computed; Febrile Neutropenia; Sensitivity and Specificity
PubMed: 38363946
DOI: 10.1097/MD.0000000000036941 -
Scientific Reports Feb 2024Ramucirumab plus docetaxel (RD) can cause febrile neutropenia (FN), which frequently requires the prophylactic administration of pegfilgrastim. However, the effects of...
Ramucirumab plus docetaxel (RD) can cause febrile neutropenia (FN), which frequently requires the prophylactic administration of pegfilgrastim. However, the effects of prophylactic pegfilgrastim on FN prevention, therapeutic efficacy, and prognosis after RD have not been fully evaluated in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred and eighty-eight patients with advanced NSCLC who received RD as second-line therapy after platinum-based chemotherapy plus PD-1 blockade were included. Patients were divided into groups with and without prophylactic pegfilgrastim, and adverse events, efficacy, and prognosis were compared between both groups. Of the 288 patients, 247 received prophylactic pegfilgrastim and 41 did not. The frequency of grade 3/4 neutropenia was 62 patients (25.1%) in the pegfilgrastim group and 28 (68.3%) in the control group (p < 0.001). The frequency of FN was 25 patients (10.1%) in the pegfilgrastim group and 10 (24.4%) in the control group (p = 0.018). The objective response rate was 31.2% and 14.6% in the pegfilgrastim and control groups (p = 0.039), respectively. The disease control rate was 72.9% in the pegfilgrastim group and 51.2% in the control group (p = 0.009). Median progression free survival was 4.3 months in the pegfilgrastim group and 2.5 months in the control group (p = 0.002). The median overall survival was 12.8 and 8.1 months in the pegfilgrastim and control groups (p = 0.004), respectively. Prophylactic pegfilgrastim for RD reduced the frequency of grade 3/4 neutropenia and febrile neutropenia and did not appear to be detrimental to patient outcome RD.Clinical Trial Registration Number: UMIN000042333.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Ramucirumab; Docetaxel; Lung Neoplasms; Polyethylene Glycols; Leukopenia; Febrile Neutropenia; Antineoplastic Combined Chemotherapy Protocols; Granulocyte Colony-Stimulating Factor; Filgrastim
PubMed: 38360906
DOI: 10.1038/s41598-024-54166-x -
Annals of Clinical Microbiology and... Feb 2024Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The...
Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.
BACKGROUND
Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres.
METHODS
We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution.
RESULTS
We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens.
CONCLUSIONS
The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.
Topics: Humans; Child; Anti-Bacterial Agents; Incidence; Bayes Theorem; Hospitals, Pediatric; Piperacillin, Tazobactam Drug Combination; Microbial Sensitivity Tests; Bacteria; Italy; Febrile Neutropenia
PubMed: 38360651
DOI: 10.1186/s12941-024-00673-8 -
Orphanet Journal of Rare Diseases Feb 2024Inherited Metabolic Diseases (IMD) encompass a diverse group of rare genetic conditions that, despite their individual rarity, collectively affect a substantial... (Review)
Review
Inherited Metabolic Diseases (IMD) encompass a diverse group of rare genetic conditions that, despite their individual rarity, collectively affect a substantial proportion, estimated at as much as 1 in 784 live births. Among their wide-ranging clinical manifestations, cytopenia stands out as a prominent feature. Consequently, IMD should be considered a potential diagnosis when evaluating patients presenting with cytopenia. However, it is essential to note that the existing scientific literature pertaining to the link between IMD and cytopenia is limited, primarily comprising case reports and case series. This paucity of data may contribute to the inadequate recognition of the association between IMD and cytopenia, potentially leading to underdiagnosis. In this review, we synthesize our findings from a literature analysis along with our clinical expertise to offer a comprehensive insight into the clinical presentation of IMD cases associated with cytopenia. Furthermore, we introduce a structured diagnostic approach underpinned by decision-making algorithms, with the aim of enhancing the early identification and management of IMD-related cytopenia.
Topics: Humans; Cytopenia; Metabolic Diseases; Neutropenia
PubMed: 38355710
DOI: 10.1186/s13023-024-03074-4 -
BMC Medical Informatics and Decision... Feb 2024Diagnostic codes are commonly used as inputs for clinical prediction models, to create labels for prediction tasks, and to identify cohorts for multicenter network...
BACKGROUND
Diagnostic codes are commonly used as inputs for clinical prediction models, to create labels for prediction tasks, and to identify cohorts for multicenter network studies. However, the coverage rates of diagnostic codes and their variability across institutions are underexplored. The primary objective was to describe lab- and diagnosis-based labels for 7 selected outcomes at three institutions. Secondary objectives were to describe agreement, sensitivity, and specificity of diagnosis-based labels against lab-based labels.
METHODS
This study included three cohorts: SickKids from The Hospital for Sick Children, and StanfordPeds and StanfordAdults from Stanford Medicine. We included seven clinical outcomes with lab-based definitions: acute kidney injury, hyperkalemia, hypoglycemia, hyponatremia, anemia, neutropenia and thrombocytopenia. For each outcome, we created four lab-based labels (abnormal, mild, moderate and severe) based on test result and one diagnosis-based label. Proportion of admissions with a positive label were presented for each outcome stratified by cohort. Using lab-based labels as the gold standard, agreement using Cohen's Kappa, sensitivity and specificity were calculated for each lab-based severity level.
RESULTS
The number of admissions included were: SickKids (n = 59,298), StanfordPeds (n = 24,639) and StanfordAdults (n = 159,985). The proportion of admissions with a positive diagnosis-based label was significantly higher for StanfordPeds compared to SickKids across all outcomes, with odds ratio (99.9% confidence interval) for abnormal diagnosis-based label ranging from 2.2 (1.7-2.7) for neutropenia to 18.4 (10.1-33.4) for hyperkalemia. Lab-based labels were more similar by institution. When using lab-based labels as the gold standard, Cohen's Kappa and sensitivity were lower at SickKids for all severity levels compared to StanfordPeds.
CONCLUSIONS
Across multiple outcomes, diagnosis codes were consistently different between the two pediatric institutions. This difference was not explained by differences in test results. These results may have implications for machine learning model development and deployment.
Topics: Humans; Delivery of Health Care; Hyperkalemia; Machine Learning; Neutropenia; Sensitivity and Specificity
PubMed: 38355486
DOI: 10.1186/s12911-024-02449-8 -
The Journal of Veterinary Medical... Apr 2024A mixed-breed, 8-year-old male dog developed neutropenia, thrombocytopenia, and hyperglobulinemia. Bone marrow hyperplasia and splenic plasmacytosis were cytologically...
A mixed-breed, 8-year-old male dog developed neutropenia, thrombocytopenia, and hyperglobulinemia. Bone marrow hyperplasia and splenic plasmacytosis were cytologically observed. The dog had never been outside of Tokyo or Shizuoka Prefecture. Splenectomy was performed to confirm and remove the cause of splenic plasmacytosis. A histopathological diagnosis of splenic plasmacytoma was made; however, serum protein electrophoresis showed polyclonal gammopathy. Further screening was performed, and Ehrlichia canis infection was confirmed. The dog was treated with doxycycline for 5 weeks. After the antibiotic therapy, no relapse of neutropenia, thrombocytopenia, hyperglobulinemia, or positive polymerase chain reaction result of E. canis infection was observed for 3 years. Careful attention should be given to ehrlichiosis when exploring the cause of pancytopenia or hyperglobulinemia, regardless of the travel history.
Topics: Male; Dogs; Animals; Ehrlichia canis; Japan; Ehrlichiosis; Thrombocytopenia; Neutropenia; Dog Diseases; Ehrlichia
PubMed: 38355119
DOI: 10.1292/jvms.23-0486 -
Molecular Genetics and Metabolism Nov 2023Glycogen storage disease type Ib (GSD1b) and G6PC3-deficiency are rare autosomal recessive diseases caused by inactivating mutations in SLC37A4 (coding for G6PT) and...
Glycogen storage disease type Ib (GSD1b) and G6PC3-deficiency are rare autosomal recessive diseases caused by inactivating mutations in SLC37A4 (coding for G6PT) and G6PC3, respectively. Both diseases are characterized by neutropenia and neutrophil dysfunction due to the intracellular accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P), a potent inhibitor of hexokinases. We recently showed that the use of SGLT2 inhibitor therapy to reduce tubular reabsorption of its precursor, 1,5-anhydroglucitol (1,5-AG), a glucose analog present in blood, successfully restored the neutropenia and neutrophil function in G6PC3-deficient and GSD1b patients. The intra-individual variability of response to the treatment and the need to adjust the dose during treatment, especially in pediatric populations, can only be efficiently optimized if the concentration of 1,5-AG in blood is monitored during treatment, together with the patients' clinical signs and symptoms. Monitoring the 1,5-AG levels would be greatly simplified if it could be performed on dry blood spots (DBS) which are easy to collect, store and transport. The challenge is to know if a suitable method can be developed to perform accurate and reproducible assays for 1,5-AG using DBS. Here, we describe and validate an assay that quantifies 1,5-AG in DBS using isotopic dilution quantitation by LC-MS/MS that should greatly facilitate patients' follow-up. 1,5-AG levels measured in plasma and DBS give comparable values. This assay was used to monitor the levels of 1,5-AG in DBS from 3 G6PC3-deficient and 6 GSD1b patients during treatment with SGLT2 inhibitors. We recommend this approach to verify the adequate therapeutical response and compliance to the treatment in G6PC3-deficient and GSD1b patients treated with SGLT2 inhibitors.
Topics: Child; Humans; Sodium-Glucose Transporter 2 Inhibitors; Chromatography, Liquid; Tandem Mass Spectrometry; Glycogen Storage Disease Type I; Neutropenia; Glucose-6-Phosphatase; Phosphoric Monoester Hydrolases; Monosaccharide Transport Proteins; Antiporters; Deoxyglucose
PubMed: 38353183
DOI: 10.1016/j.ymgme.2023.107712 -
Scientific Reports Feb 2024This single-arm, multi-center clinical trial aimed to evaluate the safety, tolerability, DLT, recommended dose (RD), preliminary efficacy, and pharmacokinetics (PK)...
This single-arm, multi-center clinical trial aimed to evaluate the safety, tolerability, DLT, recommended dose (RD), preliminary efficacy, and pharmacokinetics (PK) characteristics of lurbinectedin, a selective inhibitor of oncogenic transcription, in Chinese patients with advanced solid tumors, including relapsed SCLC. Patients with advanced solid tumors were recruited in the dose-escalation stage and received lurbinectedin in a 3 + 3 design (two cohorts: 2.5 mg/m and 3.2 mg/m, IV, q3wk). The RD was expanded in the following dose-expansion stage, including relapsed SCLC patients after first-line platinum-based chemotherapy. The primary endpoints included safety profile, tolerability, DLT, RD, and preliminary efficacy profile, while the secondary endpoints included PK characteristics. In the dose-escalation stage, ten patients were included, while one patient had DLT in the 3.2 mg/m cohort, which was also the RD for the dose-expansion stage. At cutoff (May 31, 2022), 22 SCLC patients were treated in the ongoing dose-expansion stage, and the median follow-up was 8.1 months (range 3.0-11.7). The most common grade ≥ 3 treatment-related adverse events (TRAEs) included neutropenia (77.3%), leukopenia (63.6%), thrombocytopenia (40.9%), anemia (18.2%), and ALT increased (18.2%). The most common severe adverse events (SAEs) included neutropenia (27.3%), leukopenia (22.7%), thrombocytopenia (18.2%), and vomiting (9.1%). No treatment-related deaths occurred. The Independent Review Committee (IRC)-assessed ORR was 45.5% (95% CI 26.9-65.3). Lurbinectedin at the RD (3.2 mg/m) showed manageable safety and acceptable tolerability in Chinese patients with advanced solid tumors, and demonstrates promising efficacy in Chinese patients with SCLC as second-line therapy.Trial registration: This study was registered with ClinicalTrials.gov NCT04638491, 20/11/2020.
Topics: Humans; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carbolines; China; Heterocyclic Compounds, 4 or More Rings; Lung Neoplasms; Neutropenia; Small Cell Lung Carcinoma; Thrombocytopenia
PubMed: 38351146
DOI: 10.1038/s41598-024-54223-5 -
Cancer Medicine Jan 2024A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The...
PURPOSE
A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study.
METHODS
Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m per day) and cisplatin (70 mg/m per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m per day) on days 1-5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN.
RESULTS
Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed.
CONCLUSION
Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.
Topics: Humans; Cisplatin; Docetaxel; Fluorouracil; Neoadjuvant Therapy; Antineoplastic Combined Chemotherapy Protocols; Esophageal Neoplasms; Neutropenia; Polyethylene Glycols; Anti-Bacterial Agents; Filgrastim
PubMed: 38348961
DOI: 10.1002/cam4.6974