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Although chimeric antigen receptor (CAR) T cell therapy represents a transformative immunotherapy, it is also associated with distinct toxicities that contribute to morbidity and mortality. In this systematic review and meta-analysis, we searched MEDLINE, Embase and CINAHL (Cochrane) for reports of nonrelapse mortality (NRM) after CAR T cell therapy in lymphoma and multiple myeloma up to March 2024. After extraction of causes and numbers of death, we analyzed NRM point estimates using random-effect models. We identified 7,604 patients across 18 clinical trials and 28 real-world studies. NRM point estimates varied across disease entities and were highest in patients with mantle-cell lymphoma (10.6%), followed by multiple myeloma (8.0%), large B cell lymphoma (6.1%) and indolent lymphoma (5.7%). Entity-specific meta-regression models for large B cell lymphoma and multiple myeloma revealed that axicabtagene ciloleucel and ciltacabtagene autoleucel were independently associated with increased NRM point estimates, respectively. Of 574 reported nonrelapse deaths, over half were attributed to infections (50.9%), followed by other malignancies (7.8%) and cardiovascular/respiratory events (7.3%). Conversely, the CAR T cell-specific side effects, immune effector cell-associated neurotoxicity syndrome/neurotoxicity, cytokine release syndrome and hemophagocytic lymphohistiocytosis, represented only a minority of nonrelapse deaths (cumulatively 11.5%). Our findings underline the critical importance of infectious complications after CAR T cell therapy and support the comprehensive reporting of NRM, including specific causes and long-term outcomes.
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BACKGROUND: Fever of unknown origin and inflammation of unknown origin are highly challenging diagnostic conditions. The current practice for evaluating patients is to conduct a positron emission tomography-computed tomography (PET-CT) scan as either a first- or a second-line modality. We aimed to assess the contributory effect of PET-CT to the diagnosis and compare it with the contributory effect of CT alone. METHODS: We performed a systematic review and meta-analysis. We included all cohorts that examined the contribution of PET-CT to the investigation of classical fever of unknown origin and inflammation of unknown origin. The primary outcome was the contribution of PET-CT to the final diagnosis. Secondary outcomes were sensitivity and specificity of PET-CT and CT scans, and contribution of a CT scan. We pooled the results of all studies and calculated the pooled contributory effect of PET-CT. RESULT: Thirty-six studies (3516 patients) were included in the systematic review. The pooled contribution of PET-CT was 75.4%. The compiled sensitivity and specificity values for all studies were 85.9% and 59.5%, respectively. Five studies (405 patients) compared between the PET-CT component and the total body CT component. The pooled contribution of a CT scan was 68%. The summed sensitivity and specificity values of a CT scan for all studies were 63.1% and 84.4%, respectively. CONCLUSIONS: PET-CT has a contributory effect of 75% for the diagnosis of fever of unknown origin and inflammation of unknown origin. PET-CT had superior sensitivity and inferior specificity vs the CT scan.
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Fièvre d'origine inconnue , Fluorodésoxyglucose F18 , Inflammation , Tomographie par émission de positons couplée à la tomodensitométrie , Radiopharmaceutiques , Sensibilité et spécificité , Humains , Fièvre d'origine inconnue/étiologie , Fièvre d'origine inconnue/imagerie diagnostique , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Inflammation/imagerie diagnostiqueRÉSUMÉ
INTRODUCTION: Inflammatory bowel disease (IBD) patients are three-times more likely to develop venous thromboembolism (VTE), and guidelines recommend prophylaxis during all hospitalizations. In this systematic review we sought to assess for the benefits and risks of VTE prophylaxis in hospitalized IBD patients. METHODS: We performed a systematic review and meta-analysis. We searched MEDLINE and others up to 2/2022, for studies on IBD inpatients treated with prophylactic anti-coagulation during hospitalization, compared to no prophylaxis. Primary efficacy and safety outcomes were any VTE and major bleeding, respectively. Results were pooled using random-effects models, calculating odds-ratios (OR) and 95% confidence-intervals (CI). The ROBINS-I tool was used to assess bias. RESULTS: We extracted data from 18 observational studies, and two randomized-trial subgroups. The studies were highly variable regarding the included populations, interventions, and outcome definitions. Meta-analysis of all studies showed a non-significant effect of prophylaxis on VTEs (OR 0.97[95%CI 0.49-1.95]). An analysis of eight lower-risk-of-bias studies showed a significant reduction in VTEs (OR 0.27[95%CI 0.13-0.55), number needed to treat(NNT) 34.8[95%CI 26.8-49.8]. A significant protective effect persisted in several subgroups. Major-bleeding was reported in three studies and showed a significant increase with prophylaxis (OR 2.02[95%CI 1.11-3.67], number needed to harm(NNH) 113.6[95%CI 40.7-very-large-number]). CONCLUSIONS: In studies with lower-risk-of-bias, a significant reduction in VTEs was shown in patients treated with VTE prophylaxis (NNT=35), which should be carefully considered against an increased major-bleeding risk (NNH=114). However current data is limited and randomized trials dedicated to IBD inpatients would aid in understating whether universal prophylaxis should be recommended.
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BACKGROUND: Venous thromboembolism (VTE) is considered a preventable cause of mortality. The evidence for the benefit of VTE prophylaxis in acute medical patients is non-conclusive. Meta-analysis of RCTs failed to demonstrate reduction of all-cause mortality, while showing higher risk of bleeding. The Israeli Ministry of Health has instructed to assess all acute medical patients for the risk for VTE using the Padua Prediction Score, without mandating prophylaxis. AIM: To evaluate the effect of filling the Padua score on clinical outcomes and VTE prophylaxis rates. METHODS: Retrospective Study was performed in Israel during the years 2014-2017. The participants were divided to Padua compliance vs non-compliance group. Primary outcome: 30-day mortality. Secondary outcomes: 90-day incidence of VTE and suspected major bleeding. A propensity-weighted logistic multiple regression was performed. RESULTS: 18,890 patients were included in the study. The fulfillment of the Padua score was associated with an increased use of VTE prophylaxis, OR 1.66 (95% CI 1.49-1.84). However, there was no reduction of mortality or VTE events, OR 1.13 (95% CI 0.97-1.31) and OR 1.22 (95% CI 0.79-1.8) respectively. Hospitalizations related to hemoglobin decrease were not statistically different between the two groups. CONCLUSIONS: Padua score for the assessment of VTE risk in medical wards was associated with higher administration of pharmacological prophylaxis without reduction in VTE or mortality rate. Its usage should be reassessed as a performance measure.
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Thromboembolisme veineux , Humains , Études rétrospectives , Thromboembolisme veineux/traitement médicamenteux , Anticoagulants/usage thérapeutique , Hospitalisation , Hôpitaux , Hémorragie/traitement médicamenteux , Facteurs de risqueRÉSUMÉ
INTRODUCTION: Atrial fibrillation or flutter (AF) is prevalent in cancer patients. Many of these patients have an indication for anticoagulation (AC) but are also at risk for developing chemotherapy-induced thrombocytopenia. There are scarce data regarding management of AC and risk of bleeding and thrombosis in cancer patients with AF and thrombocytopenia. AIM: To assess anticoagulation management and incidence of bleeding and arterial thromboembolism (ATE) in cancer patients with AF and grade 3-4 thrombocytopenia (platelets <50 × 109/L). METHODS: A retrospective cohort study included adults with active cancer, grade 3-4 thrombocytopenia and AF with CHA2DS2-VASc score ≥ 1. Patients were stratified according to AC discontinuation (No-AC) or continuation (Continue-AC) when platelets dropped below 50 × 109/L and followed for 30 days. The study outcomes were ATE (ischemic stroke, transient ischemic attack or systemic emboli) and major bleeding. Cox proportional hazards model was used to calculate hazard ratios (HR) with death as a competing risk (Fine and Gray model). RESULTS: The cohort included 131 patients; 90 in the No-AC group and 41 in the Continue-AC group. Patient characteristics were balanced between the groups. The 30-day cumulative incidence of ATE was 2 % [95 % CI 0.4 %-7 %] in the No-AC group and 2 % [0.2 %-11 %] in the Continue-AC group (HR 0.92 [95 % CI 0.09-9.88]). The 30-day cumulative incidence of major bleeding was 7.8 % [95 % CI 3.40 %-14.52 %] and 2.44 % [95 % CI 0.18 %-11.22 %] in the No-AC and Continue-AC groups, respectively (HR 3.29 [95 % CI 0.42-26.04]). CONCLUSIONS: The high rate of bleeding and low rate of ATE in thrombocytopenic cancer patients with AF suggests that holding AC during time-limited periods may be a reasonable approach.
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Fibrillation auriculaire , Tumeurs , Thrombopénie , Adulte , Humains , Fibrillation auriculaire/complications , Fibrillation auriculaire/traitement médicamenteux , Études rétrospectives , Thrombopénie/complications , Tumeurs/complications , Tumeurs/traitement médicamenteux , Hémorragie/induit chimiquement , Anticoagulants/effets indésirablesRÉSUMÉ
BACKGROUND: Direct-acting oral anticoagulants (DOACs) including rivaroxaban and apixaban are preferred over vitamin K antagonists for the treatment of venous thromboembolism (VTE). We conducted a systematic review and a meta-analysis to compare the efficacy and safety of rivaroxaban versus apixaban in the treatment of VTE. METHODS: We conducted an electronic search for studies that directly compared treatment with rivaroxaban and apixaban in adult patients with VTE. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated and pooled using a fixed-effect model unless significant heterogeneity was present (I2 > 40%), then random-effects model was used. The primary efficacy and safety outcomes were recurrent VTE (rVTE) and major bleeding events, respectively. RESULTS: Nine observational studies were included in our meta-analysis, assessing 24,156 patients for apixaban and 38,847 for rivaroxaban. Pooling of data for our primary efficacy outcome showed a trend towards lower risk of rVTE with apixaban compared to rivaroxaban (RR 0.77, 95% CI 0.57-1.04, I2 = 53%). Analysis of our primary safety outcome showed a significantly lower risk of major bleeding with apixaban compared to rivaroxaban (RR 0.68, 95% CI 0.61-0.76, I2 = 0%). Apixaban was associated with significantly decreased risk of net clinical harm, clinically relevant non major bleeding (CRNMB) and any bleeding, compared to rivaroxaban (RR 0.75, 95% CI 0.61-0.92, I2 = 50%; RR 0.58, 95% CI 0.50-0.67, I2 = 7%; RR 0.64, 95% CI 0.59-0.70, I2 = 0%, respectively). CONCLUSIONS: Apixaban is associated with a significantly lower risk of major bleeding compared to rivaroxaban for treatment of VTE. Given the limitations of the existing evidence, further interventional studies comparing the two drugs are needed.
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Inhibiteurs du facteur Xa , Hémorragie , Pyrazoles , Pyridones , Rivaroxaban , Thromboembolisme veineux , Rivaroxaban/usage thérapeutique , Rivaroxaban/effets indésirables , Humains , Pyridones/effets indésirables , Pyridones/usage thérapeutique , Pyridones/administration et posologie , Thromboembolisme veineux/traitement médicamenteux , Pyrazoles/usage thérapeutique , Pyrazoles/effets indésirables , Hémorragie/induit chimiquement , Inhibiteurs du facteur Xa/usage thérapeutique , Inhibiteurs du facteur Xa/effets indésirables , Études observationnelles comme sujet , Résultat thérapeutiqueRÉSUMÉ
INTRODUCTION: Influenza virus causes significant global annual morbidity and mortality. Thrombocytopenia is recognized as a poor prognostic factor in sepsis and is associated with mortality, while lymphopenia has been established as a poor prognostic factor in other viral infections. We aimed to assess the incidence of thrombocytopenia and lymphopenia in seasonal influenza and their effect on clinical outcomes. METHODS: This single-center, retrospective, cohort study included consecutive adult patients, hospitalized in Rabin Medical Center between October 2017 and April 2018, with laboratory-confirmed influenza. Patients were grouped according to blood counts on admission: (1) thrombocytopenia (<150 K/mL), (2) lymphopenia (<0.5 K/mL), and (3) both thrombocytopenia and lymphopenia. Patients without thrombocytopenia and lymphopenia were designated as controls. The primary outcome was 30-day all-cause mortality. Risk factors were identified by univariable and multivariable analyses, using logistic regression and reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 625 patients were included, 112 (18%) had thrombocytopenia, 98 (15.6%) had lymphopenia, and 107 (17%) had both. The crude 30-day all-cause mortality was 7.6% (48/625). Mortality rates were 7.1% (8/112) for the thrombocytopenia group, 11.2% (11/98) for the lymphopenia group, and 14.9% (16/107) for patients with both versus 4.2% (13/308) in the control (p = 0.000 for all). In a multivariable regression model, significant thrombocytopenia (<100 K/µL) [OR 5.07 (95% CI 1.5-16.2)], age [OR 1.07 (95% CI 1.02-1.11)], time to oseltamivir [OR 1.006 (95% CI 1.002-1.11)], and significant respiratory support [OR 8.85 (3.4-22.6)] were associated with 30-day all-cause mortality. CONCLUSION: Patients hospitalized with seasonal influenza and thrombocytopenia <100 K/mL on admission, have an increased 30-day all-cause mortality.
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Maladies de la moelle osseuse , Grippe humaine , Lymphopénie , Orthomyxoviridae , Thrombopénie , Adulte , Humains , Études rétrospectives , Grippe humaine/complications , Études de cohortes , Lymphopénie/étiologie , Thrombopénie/complicationsRÉSUMÉ
INTRODUCTION: Extracorporeal photopheresis (ECP) is considered an effective treatment for patients with chronic graft vs host disease (cGVHD) and demonstrates efficacy in ameliorating GVHD. The mechanism by which ECP acts against cGVHD is not fully understood. Preliminary observations have hinted at the potential involvement of neutrophil extracellular traps (NETs) formation in the pathogenesis of cGVHD. We aimed to assess the influence of ECP on the formation of NETs in patients with cGVHD as a potential mechanism in this setting. METHODS: Patients treated with ECP for cGVHD at the Rabin Medical Center were included in this study. Blood samples were obtained at three different time points: before starting an ECP cycle, at the end of the first day of treatment, and 24 h following the initiation of the ECP treatment cycle. Neutrophils were harvested from all blood samples. NET formation was assessed by measurement of NET-bound specific neutrophil elastase activity and by immunofluorescence staining. RESULTS: Six patients (two females and four males) with cGVHD were included in the study. We observed a significant increase in NET formation among all six patients following ECP. Net-bound specific neutrophil elastase activity was elevated from a median value of 2.23 mU/mL (interquartile range [IQR] 2.06-2.47 mU/mL) at baseline to a median value of 13.06 mU/mL (IQR 10.27-15.97 mU/mL) immediately after the treatment and to a peak median value of 14.73 mU/mL (IQR 9.6-22.38 mU/mL) 24 h following the initiation of the ECP cycle. A qualitative assessment of NET formation using immunofluorescence staining has demonstrated markedly increased expression of citrullinated histone H3, a marker of NET formation, following ECP treatment. CONCLUSIONS: Our preliminary data indicate that ECP induces NET formation among patients with cGVHD. The contribution of increased NET formation to the therapeutic effect of cGVHD should be further investigated.
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Guidelines recommend intravenous (IV) ceftriaxone at a dose of 1-2 g/d as empirical treatment in adults hospitalized with community acquired pneumonia (CAP), with the addition of macrolide. We examined whether 1 g/d of IV ceftriaxone is associated with similar clinical outcomes to those of 2 g/d. This is a single-center, retrospective, cohort study of all adult patients hospitalized at Rabin Medical Center between 2015 and 2018 with CAP. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified by univariable and multivariable analyses, using logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 2045 patients were treated with IV ceftriaxone 1 g/d and were and compared to 1944 patients who were treated with 2 g/d. The groups were comparable in their baseline characteristics and their clinical presentation. The 30-day all-cause mortality rate was similar between the groups (301/2045 (14.7%) for 1 g/d vs. 312/1944 (16.0%) for 2 g/d, p = 0.24). The rate of C. difficile infection (CDI) was significantly decreased with 1 g/d compared to 2 g/d (4/2045 (0.2%) vs. 12/1944 (0.6%), p = 0.03) and the length of stay was significantly shorter (median 4 days interquartile range (IQR) 3-7 vs. 5 days IQR 3-8, p = 0.02). None of the blood isolates of Streptococcus pneumoniae were penicillin or ceftriaxone resistant. For hospitalized patients with CAP, IV ceftriaxone 1 g/d was associated with similar mortality rates as IV ceftriaxone 2 g/d, with a decreased rate of CDI and shorter length of stay. Ceftriaxone 1 g/d may be sufficient to treat patients with CAP in countries with low prevalence of drug resistant Streptococcus pneumoniae.
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Clostridioides difficile , Infections communautaires , Pneumopathie infectieuse , Adulte , Humains , Ceftriaxone/pharmacologie , Ceftriaxone/usage thérapeutique , Études rétrospectives , Études de cohortes , Résultat thérapeutique , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Pneumopathie infectieuse/traitement médicamenteux , Pneumopathie infectieuse/épidémiologie , Infections communautaires/traitement médicamenteux , Infections communautaires/épidémiologieRÉSUMÉ
The GALLIUM study showed a progression-free survival advantage of 7% in favor of obinutuzumab vs. rituximab-based immunochemotherapies as first-line therapy in follicular lymphoma (FL) patients. Yet, the toxicity appears to be increased with obinutuzumab-based therapy. This is a multicenter retrospective-cohort study including adult FL patients comparing the toxicity of first-line rituximab vs. obinutuzumab-based chemo-immunotherapies (R and O groups, respectively). We compared the best standard-of-care therapy used per time period, before and after obinutuzumab approval. The primary outcome was any infection during induction and 6 months post-induction. Secondary outcomes included rates of febrile neutropenia, severe and fatal infections, other adverse events, and all-cause mortality. Outcomes were compared between groups. A total of 156 patients were included in the analysis, 78 patients per group. Most patients received bendamustine (59%) or CHOP (31.4%) as adjacent chemotherapy. Half of the patients received growth-factor prophylaxis. Overall, 69 patients (44.2%) experienced infections, and a total of 106 infectious episodes were recorded. Patients in the R and O groups had similar rates of any infection (44.8% and 43.5%, p = 1), severe infections (43.3% vs. 47.8%, p = 0.844), febrile neutropenia (15% vs. 19.6%, p = 0.606), and treatment discontinuation, as well as similar types of infections. No covariate was associated with infection in multivariable analysis. No statistically significant difference was evident in adverse events of grades 3-5 (76.9% vs. 82%, p = 0.427). To conclude, in this largest real-life study of first-line treated FL patients comparing R- to O-based therapy, we did not observe any difference in toxicity during the induction and 6 months post-induction period.
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Neutropénie fébrile , Lymphome folliculaire , Adulte , Humains , Rituximab/effets indésirables , Lymphome folliculaire/traitement médicamenteux , Études rétrospectives , Études de cohortes , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Chlorhydrate de bendamustine , Immunothérapie , Neutropénie fébrile/induit chimiquementRÉSUMÉ
Data are needed on direct oral anticoagulants (DOACs) for the treatment of venous thromboembolism (VTE) in hematological malignancies (HM). Retrospective studies to date lacked a control group and did not focus on patients with VTE. Out aim was to assess the incidence of VTE recurrence and bleeding in HM patients treated with low molecular weight heparin (LMWH) or DOACs for acute VTE. This is a retrospective cohort study including patients with active HM and newly-diagnosed VTE, indexed on the first day of anticoagulation and followed for 12 months. The outcome was a composite of recurrent VTE, major bleeding or clinically relevant non-major bleeding. Cumulative incidence [95% confidence interval (CI)] was calculated for each anticoagulation group (LMWH, DOAC) and hazard ratios (HR) were calculated using cox-proportional hazards model, with death as a competing risk. 143 HM patients treated with LMWH (96) or DOACs (47) for acute VTE were included. The most common HM types were lymphoma in 83 (58%) and plasma cell dyscrasia in 32 (22.3%). The 12-month cumulative incidence of the composite outcome was 24.2% (95% CI 15.9-33.5%; n = 22) in the LMWH group and 18.5% (8.5-31.5%; n = 8) in the DOAC group (HR 1.51 [0.695-3.297]). Two recurrent VTE occurred (both in the DOAC group while off-treatment). Nine (9.4%) LMWH-treated patients had major bleeding compared to 1 (2.1%) DOAC-treated patient (HR 4.85 [0.64-36.56]). This study generates the hypothesis that DOACs may be a safe and effective alternative to LMWH for VTE in patients with HM types represented in the study.
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Tumeurs hématologiques , Tumeurs , Thromboembolisme veineux , Humains , Héparine bas poids moléculaire/effets indésirables , Thromboembolisme veineux/étiologie , Études rétrospectives , Tumeurs/traitement médicamenteux , Anticoagulants/effets indésirables , Hémorragie/induit chimiquement , Hémorragie/épidémiologie , Tumeurs hématologiques/complications , Tumeurs hématologiques/traitement médicamenteux , Administration par voie oraleRÉSUMÉ
INTRODUCTION: We aimed to assess the natural annual trends in the levels of haemoglobin, haematocrit, and mean corpuscular volume (MCV) in a population of adults, together with the influence of different clinical parameters on these trends. METHODS: A retrospective analysis was carried out on data from a large cohort of subjects attending a screening centre in Israel. For each subject, the yearly average change of haemoglobin, haematocrit, and MCV was calculated. Statistical analysis was performed for the whole cohort and for different subgroups. RESULTS: The study included 3,551 subjects. The average annual rates of decline were found to be -0.0550 g/dL (95% confidence interval [CI] -0.0590 g/dL to -0.0503 g/dL) and -0.097% (95% CI -0.112% to -0.083%) for haemoglobin and haematocrit, respectively. An average annual increase in the MCV level by 0.184 fL (95% CI 0.168 fL-0.200 fL) was found. Among men, the rate of decline in haemoglobin was found to be twice as high compared with women -0.06 g/dL versus -0.03 g/dL, respectively (p = 0.0063). In a multivariate analysis, gender remained the only parameter significantly associated with the annual decline of haemoglobin (p = 0.0001). CONCLUSION: An annual average decrease in the levels of haemoglobin and haematocrit together with an annual increase in MCV was found. These changes were more prominent in men.
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Index érythrocytaires , Hémoglobines , Mâle , Adulte , Femelle , Humains , Hématocrite , Études rétrospectives , Hémoglobines/analyse , IsraëlRÉSUMÉ
BACKGROUND: Previous studies demonstrated a 'weekend effect' and a 'night effect' of increased mortality among patients admitted during weekends or night shifts, presumably due to understaffing. AIMS: To examine whether death during hospitalisation follows a similar effect regardless of admission time. METHODS: A retrospective cohort study among deceased patients hospitalised in the internal medicine wing of a tertiary medical centre in Israel, between 2019 and 2020. Demographic and medical data were retrieved from electronic medical charts. Causes of death were specifically categorised. We applied statistical models to test for differences in mortality using incidence rate ratio (IRR) according to the day, time and cause of death. RESULTS: One thousand, two hundred and seventy-eight deceased patients were included. All-cause mortality was similar between weekends and weekdays. When sepsis was the cause of death, higher IRR were demonstrated on Fridays in comparison with weekdays (IRR 1.4; 95% confidence interval (CI) 1.1-1.9; P < 0.05). Other causes of death were not consistent with a 'weekend effect'. Mortality during night shifts was higher in comparison with the afternoon (IRR 1.5; 95% CI 1.3-4.7) and similar to the morning (IRR 1; 95% CI 0.9-1.2). CONCLUSION: Our study did not find a pattern of 'weekend effect' or 'night effect' on all-cause mortality among hospitalised patients in internal medicine wards. Our findings suggest that perhaps specifically death from sepsis, and not all-cause mortality, can be used as a surrogate for the measurement of understaffing or quality of care in the internal ward.
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Mortalité hospitalière , Unités hospitalières , Médecine interne , Admission du patient , Humains , Mortalité hospitalière/tendances , Hospitalisation , Études rétrospectives , Facteurs temps , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plus , Centres de soins tertiaires , Israël/épidémiologie , Admission du patient/statistiques et données numériquesRÉSUMÉ
OBJECTIVES: Ceftriaxone is recommended as first-line antibiotic treatment (with the addition of macrolide) for hospitalised adults with community acquired pneumonia (CAP). Narrower-spectrum ß-lactam as ampicillin, may be associated with comparable clinical outcomes, with less emergence of resistant pathogens or Clostridioides difficile infection (CDI). We aimed to examine whether ampicillin and ceftriaxone (with the addition of macrolides for both arms) are comparable for the treatment of hospitalized adults due to CAP. METHODS: This was a single center, observational cohort study. We included adult patients who were hospitalized in internal medicine wards due to CAP and were treated with either ceftriaxone or ampicillin with the addition of macrolide. A propensity-score model was used. The primary outcome was 30-day all-cause mortality. A multivariable logistic regression analysis and Kaplan-Meier survival analysis was performed. We performed subgroup analyses for the main outcome based on CURB-65 score and age. RESULTS: A total of 1586 patients fulfilled the inclusion criteria. There was no difference in 30-day mortality rate in the total cohort (28/233 vs. 208/1353 in ampicillin and ceftriaxone arm, respectively; p = 0.184). In the propensity matched cohort (197 in ampicillin and 394 in ceftriaxone arm), there was no significant difference in 30-day all-cause mortality between treatment groups in multivariable analysis of the main model (OR 0.67, 95% CI, 0.37-1.2; p = 0.189) and Kaplan-Meier survival analysis (p = 0.108). Thirty-day mortality rate was (19/197 vs. 57/394, in ampicillin and ceftriaxone arms, respectively; p = 0.108) Patients who were treated with ampicillin experienced significantly lower rates of CDI (0/197, 0% vs. 8/394, 2%; p = 0.044). DISCUSSION: Ampicillin was associated with comparable clinical outcomes in comparison to ceftriaxone for patients who were hospitalized due to CAP. Ampicillin was associated with significantly lower rate of CDI. Results need to be confirmed by more robust study designs.
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Infections communautaires , Pneumopathie infectieuse , Adulte , Humains , Ceftriaxone/usage thérapeutique , Études de cohortes , Antibactériens/usage thérapeutique , Pneumopathie infectieuse/traitement médicamenteux , Ampicilline/usage thérapeutique , Infections communautaires/traitement médicamenteux , Macrolides/usage thérapeutiqueRÉSUMÉ
Immune thrombocytopenia (ITP), is an acquired autoimmune disorder characterized by the destruction of platelets and megakaryocytes, resulting in thrombocytopenia (platelet count <100 × 109/L). This review focuses on the diagnosis and current management of ITP. The diagnosis of ITP is based principally on the exclusion of other causes of isolated thrombocytopenia using patient history, physical examination, blood count, and evaluation of the peripheral blood film. The clinical treatment goals should be to resolve bleeding events and to prevent severe bleeding episodes. The platelet count should be improved to attain a minimum of > 20-30 × 109/L. Therapy should be given as an inpatient in newly diagnosed ITP with a platelet count of > 20 × 109/L or if there is active bleeding. Corticosteroids are considered the standard initial treatment for newly diagnosed patients. Subsequent medical therapies with robust evidence include thrombopoietin receptor agonists (TPO-RAs), rituximab and fostamatinib. Surgical therapy with splenectomy may be considered for patients failing medical therapy. The choice between therapy options is highly dependent upon patient values and preferences.
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Purpura thrombopénique idiopathique , Thrombopénie , Humains , Purpura thrombopénique idiopathique/diagnostic , Purpura thrombopénique idiopathique/thérapie , Thrombopénie/diagnostic , Numération des plaquettes , Hormones corticosurrénaliennes/usage thérapeutique , Rituximab/usage thérapeutique , Thrombopoïétine/usage thérapeutiqueRÉSUMÉ
Spontaneous resolution is common in patients with classic fever of unknown origin (FUO). Identifying predictors of spontaneous resolution could reduce the usage of unnecessary, invasive tests or empirical therapy, and furthermore reduce patient anxiety. Identify predictors associated with spontaneous resolution of FUO. A single center, retrospective, cohort study. All hospitalized patients who underwent an [18F] FDG PET-CT scan for the investigation of classical FUO between 1/2012 and 1/2020 were included. We compared patients with spontaneous resolution of fever and clinical symptoms, to those who were diagnosed with a specific etiology of FUO (subdivided to infectious diseases, non-infectious inflammatory diseases (NIID), and malignancies). Epidemiologic characteristics as well as laboratory and PETCT study results were compared. Variables that were found to be associated with spontaneous resolution of FUO on univariate analysis (p < 0.1) were entered into a multivariable regression analysis. The results are reported as odds ratios (OR) and 95% confidence intervals (CI). A total of 303 patients were hospitalized for the investigation of classical FUO and underwent complete assessment. Fever resolved without a diagnosis in 84/303 patients (28%). Variables that were associated with spontaneous resolution of FUO on multivariable analysis included: no anemia, no hypoalbuminemia and no pathological FDG uptake on PET-CT. In 17.8% (15/84) of studies, PET-CT yielded false-positive results that led to additional unnecessary, invasive investigation. Patients without anemia or hypoalbuminemia, and those without uptake on PET-CT are more likely to have spontaneous resolution of classical FUO.
Sujet(s)
Fièvre d'origine inconnue , Tomographie par émission de positons couplée à la tomodensitométrie , Humains , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Fluorodésoxyglucose F18 , Fièvre d'origine inconnue/étiologie , Fièvre d'origine inconnue/diagnostic , Études rétrospectives , Études de cohortes , Tomodensitométrie/méthodes , Tomographie par émission de positons/méthodesRÉSUMÉ
OBJECTIVES: To evaluate the role of additional chemotherapy before autologous hematopoietic cell transplantation (HCT) in patients with relapse/refractory diffuse large B-cell lymphoma (DLBCL) who achieve partial remission following first salvage therapy. METHODS: We conducted a multicenter retrospective study of all adult patients with DLBCL who underwent HCT between 2008 and 2020 and achieved partial response (PR) after the first salvage and were either referred directly to HCT (n = 47) or received additional salvage therapy before HCT (n = 22). RESULTS: Post-HCT CR rate and progression-free survival were comparable between the two groups (66% vs. 68%, p = .86 and median not reached vs. 10.2 months [95% confidence interval, CI 7.1-12.3], p = .27, respectively). Median overall survival (OS) and estimated 3-year OS favored patients who were directly referred to HCT (105.8 [95% CI 63-148] months vs. 14.5 [95% CI 0-44] months, p = .035, and 65% [95% CI 51%-75%] vs. 40% [95% CI 21%-53%], p = .035, respectively). In Cox regression model, while International Prognostic Index and primary refractory versus relapse disease did not impact OS, allocation to a second salvage regimen and older age were both associated with inferior survival (hazard ratio [HR] = 2.57 95% CI 1.1-5.8, p = .023 and HR = 1.04 95% CI 0.99-1.2, p = .064, respectively). CONCLUSIONS: Referring patients with chemotherapy-sensitive disease in PR directly to HCT is associated with better OS compared to those receiving additional lines of treatment.
Sujet(s)
Transplantation de cellules souches hématopoïétiques , Lymphome B diffus à grandes cellules , Lymphome malin non hodgkinien , Récidive tumorale locale , Adulte , Humains , Lymphome B diffus à grandes cellules/traitement médicamenteux , Lymphome malin non hodgkinien/traitement médicamenteux , Récidive tumorale locale/traitement médicamenteux , Études rétrospectives , Transplantation autologueRÉSUMÉ
Aggressive B cell lymphoma often requires prompt steroid treatment, even before baseline 18f-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and definitive treatment, to alleviate symptoms or prevent organ damage. Since lymphoma is a steroid-sensitive malignancy, there are concerns that steroids might affect the results of FDG PET/CT and decrease its diagnostic yield. The aim of the current study was to evaluate the effect of steroids administered before baseline PET/CT on the maximum standardized uptake value (SUVmax) and additional PET/CT parameters. Retrospective review of the database in a tertiary medical center yielded 178 patients newly diagnosed with aggressive B cell lymphoma between January 2017 and May 2020 who had an available baseline FDG PET/CT scan. The cohort was divided into patients who received steroids before PET/CT (n = 47) and those who did not (n = 131), and the groups were compared for SUVmax and additional PET/CT parameters. The steroid-treated group had a higher disease stage and lactate dehydrogenase level compared to the steroid-naïve group, with a trend toward a higher international prognostic index. There was no significant between-group difference in SUVmax (P = 0.61). This finding remained consistent across steroid treatment durations and dosage regimens. Further evaluation revealed a significantly larger mean tumor volume and a trend toward a higher tumor metabolic burden in the steroid-treated group, yet no between-group difference in SUV mean or other PET/CT parameters. In this retrospective analysis of patients with aggressive B cell lymphoma, steroid prophase prior to baseline PET/CT did not decrease the diagnostic yield of the scan. However, further studies are required to fully appreciate the impact of steroids on PET CT parameters.
RÉSUMÉ
Febrile neutropenia (FN) is a major complication in patients with diffuse large B-Cell lymphoma (DLBCL). Diabetes mellitus (DM) has deleterious effects on the immune system resulting in an increased risk of infections. We evaluated patients with DLBCL who started frontline treatment with R-CHOP, and compared outcomes according to presence of DM comorbidity. Between 2013 and 2018, 218 patients with DLBCL were included. 46 patients (21%) had DM. Rate of admissions for FN was higher for patients with DM (0.7 vs. 0.46 admissions/patient, p = .016), also after age and gender-matched subgroup analysis (p = .004). Improved glycemic control during FN hospitalizations was associated with shorter hospitalizations. Metformin was associated with improved median overall survival in diabetic patients (89 vs. 64 months, p = .018). In conclusion, Patients with DLBCL and DM had higher rates of FN hospitalizations. Improved glycemic control during FN hospitalization was associated with shorter length of stay.