Impact of Prophylaxis with Aerosolized Amphotericin-B Deoxycholate (d-AmB) on Respiratory Tract Invasive Fungal Infections (IFIs) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4986-4986
Author(s):  
Enrico Morello ◽  
Irene M. Cavattoni ◽  
Pietro Fabris ◽  
Silvia Coin ◽  
Barbara Amato ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Unrelated Donor ◽  
X Rays ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Number Of Patients ◽  
Increased Risk ◽  
The Impact

Abstract Background and aims IFIs still pose major challenges in HSCT, and effective prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the impact of aerosolized d-AmB on respiratory tract IFIs in a homogeneous cohort of allogeneic HSCT patients, transplanted at our institution. Patients and methods Since 1999, 81 consecutive patients were transplanted from matched related (N=61) or unrelated donor (MUD). Analysis was performed on 74 evaluable patients, in order to monitor the prevalence of respiratory tract IFIs within 40 days after HSCT, according to current guidelines (possible, probable, proven IFIs). Conventional antifungal prophylaxis was based on the association of fluconazole (400 mg/d), plus aerosolized d-AmB (15 mg bid) in 54 out of 74 cases (73%). All the patients were screened before transplant and monitored thereafter with CT or x-rays (paranasal sinuses, thorax), surveillance swabs and galactomannan antigenemia. Chi square test was performed to evaluate correlations between variables. Results Aerosolised d-AmB was administered to 70 patients for a median time of 15 days (range 1–45). Prolonged administration was not associated with increased severe bacterial infections, nor severe adverse events were observed; only a patient developed moderate bronchial spasm. In 13 pts, aerosolized d-AmB was delivered for less than 7 days, due to worsened clinical conditions, or poor compliance. In this group, proven IFIs were diagnosed in 2 patients (1 mucormycosis and 1 fusariosis), possible aspergillosis in one and probable aspergillosis in another one. A shortened administration (<7 days) of aerosolized d-AmB was associated with an increased risk of IFIs (p=0,002). Overall, 95% of patients did not experience IFIs and nobody died due to IFIs. Nine patients had a pre-transplant nasal swab positive for Aspergillus spp., and 8 of them received Aerosolized d-AmB; subsequent surveillance swabs proved negative. On the other hand, the only patient with positive swab who was not able to receive aerosolized d-AmB due to bronchial spasm developed a possible aspergillosis. Discussion Despite the low number of patients, prolonged aerosolized d-AmB seems to play a role in preventing respiratory tract IFIs, but a randomised controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.

scholarly journals RhizomucorandScedosporiumInfection Post Hematopoietic Stem-Cell Transplant

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Dânia Sofia Marques ◽  
Carlos Pinho Vaz ◽  
Rosa Branca ◽  
Fernando Campilho ◽  
Catarina Lamelas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Increased Risk

Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due toRhizomucor sp.and rhinoencephalitis due toScedosporium apiospermum6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis), its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies).

The Impact of NOD2/CARD15, TLR and IL23R Polymorphisms on the Incidence of Infectious Complications in Allo-HSCT Recipients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2201-2201
Author(s):  
Alexandra Maria Holowiecka-Goral ◽  
Sebastian Giebel ◽  
Jerzy Wojnar ◽  
Elzbieta Pietruszka ◽  
Agnieszka Karolczyk ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Infectious Complications ◽  
Individual Risk ◽  
Unrelated Donor ◽  
X Rays ◽  
Increased Risk ◽  
Card15 Gene ◽  
The Impact

Abstract BACKGROUND: Infections and graft-vs.-host disease (GvHD) remain the major obstacles for successful allogeneic stem cell transplantation (alloHSCT). As specific immune response is profoundly suppressed during the first months after transplantation, the components of innate immunity are expected to play important role in protection against infections and modulation of GvHD. The goal of this prospective study was to evaluate the impact of NOD2/CARD15 gene, toll-like receptors (TLR), and interleukin-23 receptor (IL-23R) single nucleotide polymorphisms (SNPs), on outcome of alloHSCT, including the incidence of infectious complications and acute GvHD. All these factors were documented to take part in innate immunity. PATIENTS: One-hundred-twenty-five consecutive patients, mainly with hematological malignancies, aged 32 (18–58)y, treated with alloHSCT from HLA-matched related (n=43) or matched unrelated donor (MUD) (n=82) were analyzed. The conditioning regimen was myeloablative, GVHD prophylaxis consisted of cyclosporin, metotrexate, and, in case of MUD-HSCT, pre-transplant anti-thymocyte globulin. METHODS: Donors and recipients were tested for SNP8,12,13 of the NOD2/CARD15 gene, TLR2/753, TLR4/299, TLR4/399, TLR5/C1174T, and TLR9/1635 SNPs, as well as IL23R/11209026 SNP. Study end-points included the incidence of bacterial, fungal and clinically relevant viral infections. Infections were recognized based on clinical symptoms, microbial cultures, chest X-rays for pneumonia confirmation and in case of CMV and EBV- PCR screening. We analyzed separately infections occurring in the early, cytopenic phase and those occurring after engraftment. Additionally, the incidence of acute GvHD and survival was evaluated. RESULTS: Presence of NOD2/CARD15 SNP8 in recipient resulted in higher frequency of neutropenic pneumonia (40% vs. 6%, p=0.045) and bacterial pharyngitis (100% vs. 50%, p=0.06), as well as increased incidence of grade III-IV acute GVHD (40% vs. 7%, p=0.05), which translated into increased non-relapse mortality (60% vs. 14%, p=0.005) and decreased 2-year overall survival (20% vs. 71%, p=0.003). TLR4/299 SNP in recipient tended to increase the risk of neutropenic fever (FUO) (67% vs. 30%, p=0.06) and decrease survival (71% vs. 48%, p=0.09). TLR2/753 SNP in donor was associated with higher incidence of FUO (83% vs. 30%, p-0.01), while TLR5/C1174T SNP in recipient resulted in increased incidence of EBV infection (25% vs. 4%, p-0.05). Presence of IL23R/11209026 SNP in donor tended to increase the incidence of neutropenic pneumonias (29% vs. 6%, p=0.09). CONCLUSIONS: NOD2/CARD15, TLR, and IL23R SNPs appear to influence outcome of alloHSCT contributing to increased incidence of infections, and in case of NOD2/CARD15 SNP8 in recipient to increased risk of severe acute GVHD. The genomic analysis may allow elaboration of adequate preventive strategies based on individual risk assessment. Our results encourage for further, extended studies.

Weight Gain in the First 10 Days after Hematopoietic Stem Cell Transplantation (HSCT) Is a Risk Factor for Early Mortality

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2471-2471 ◽  
Author(s):  
Lucila Nassif Kerbauy ◽  
Erika MM Costa ◽  
Juliano Cordova Vargas ◽  
Claudia Mac Donald Bley Nascimento ◽  
Joyce E Hyppolito ◽  
...  
Keyword(s):  
Risk Factor ◽  
Weight Gain ◽  
Conditioning Regimen ◽  
Early Mortality ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Increased Risk ◽  
Inflammatory State ◽  
Unrelated Donors ◽  
The Impact

Abstract Introduction: Hematopoietic stem cell transplantation (HSCT) is an effective treatment option for patients with hematological and neoplastic diseases. Despite recent improvements, HSCT is still associated with a significant risk of mortality. Determining risk factors for death within the first 100 days after HSCT could help to identify patients who would benefit from interventions in order to decrease that risk. We have previously reported that increased fluid accumulation during conditioning chemotherapy and in the early period after HSCT was associated with decreased survival (Costa EMM et al, ASH 2013Abstract #4512). Herein, we expand that series of patients and we further analyze the impact of weight gain on early (100-days) mortality in patients who underwent HSCT at our institution. Objective: To determine the impact of weight gain during the first 10 days post-HSCT on 100 days mortality. Methods:We retrospectively reviewed the medical charts of 331 patients who underwent HSCT at our institution from January, 2007 until December, 2013. Information on patients' body weight (BW) was measured daily, starting at admission. The highest BW recorded until until the first 10 days post-SCT (D+10) was used to calculate the BW increase in relation to the baseline BW. Based on our previous study, we used a cutoff of 6% gain in BW to identify a group of patients with increased risk of complications. The primary endpoint was mortality within 100 days post HSCT. Overall survival (OS) was estimated from the time of HSCT until death, and surviving patients were censored at last follow-up. A logistic regression model and a Cox model were fit to determine variables that predicted death within 100 days and OS, respectively. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results: Median age was 43 years old (range <1 year-76 years) and 60% were male. HSC sources included autologous (46%), matched related donors (16%), matched unrelated donors (12%), cord blood units (16%) and mismatched related/unrelated donors (10%). Diagnosis included acute leukemia or chronic myeloid disorders (34%), lymphoma/multiple myeloma (42%) and non-malignant hematological disorders (24%). Twenty-one percent of patients had a ≥6% gain in BW until the first 10 days post-HSCT. These patients had developed an increased inflammatory state after the start of the conditioning regimen: there was no difference in baseline levels of C-reactive protein (4.8 mg/L vs. 7.4, p=0.37), but by D+10 patients who gained more BW had higher CRP (116.7 mg/L vs. 178.6 mg/L; p=0.01). Patients with increased gain in BW until D+10 had a decreased OS (HR 2.33, p<0.0001, 95% CI 1.45-3.73). The mortality within 100 days was 47% in the increased BW vs. 17% in the control group (p<0.0001). Among 18 patients who died within 100 days and had a ≥6% BW gain by D+10, causes of death included pneumonia (N=4), septic shock (N=9), fungal endocarditis (N=1), ischemic stroke (N=1) and disease progression (N=3). In a logistic regression analysis, after adjusting for age, sex, diagnosis and type of SCT, a ≥6% BW gain by D10 was associated with an increased risk of being dead within 100 days (coefficient 1.75; p<0.0001; 95% CI 0.90-2.61). Similarly, in a multivariate Cox analysis after adjusting for age, sex, diagnosis and type of SCT, a ≥6% BW gain by D10 was an independent risk factor for survival (HR 2.72, p<0.0001, 95% CI 1.65-4.48). A landmark analysis at D+100 revealed that the negative impact of weight gain by D+10 on survival was restricted to the first 100 days, as after this time point there was no survival difference between the two groups (HR 1.35; p=0.41; 95% CI 0.65-2.83). Conclusion: A ≥6% BW gain by D+10 is a risk factor for early mortality in both autologous and allogeneic HSCT. The most common cause of death in these patients is infectious-related complications. An increase in BW is related to the development of an inflammatory state, probably induced by the conditioning regimen. BW gain is a simple variable that can be easily used to determine prognosis of patients post-allogeneic HSCT, and further studies are needed to determine its etiology. Disclosures No relevant conflicts of interest to declare.

Impact of Pretransplant Neutropenia on Post-Transplant Outcome in Patients with Myelodysplastic Syndrome (MDS).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 599-599
Author(s):  
Bart L. Scott ◽  
J.Y. Park ◽  
B. Storer ◽  
K.A. Marr ◽  
M. Boeckh ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Fungal Infections ◽  
International Prognostic Scoring System ◽  
Bacillus Species ◽  
Fungal Colonization ◽  
Probability Of Survival ◽  
Transfusion Requirements ◽  
Increased Risk ◽  
Neutropenic Patients ◽  
The Impact

Abstract MDS comprises a spectrum of clonal hematopoietic disorders with very heterogeneous clinical courses. Several classification and scoring systems have been developed in an attempt to define subgroups of patients with similar prognoses. The International Prognostic Scoring System (IPSS) incorporates marrow myeloblast count, karyotype, and peripheral blood cytopenias. The recent addition of transfusion requirements to the IPSS (WPSS) has sharpened this prognostic tool. Isolated neutropenia is not reflected in these classifications, but bacterial and fungal colonization and infection are problems in patients with MDS. Hematopoietic cell transplantation is the only treatment strategy that has been shown to have curative potential, and many patients come to transplantation with neutropenia, particularly when the disease progresses. We wanted to determine the impact of neutropenia before transplantation on transplant success. We reviewed results in 291 patients with MDS (including MDS that had transformed to AML [tAML]), 1 to 66 (median 50) years of age, who from 1994 through 2003 were transplanted from related or unrelated donors following conditioning with myeloablative regimens. There were 178 patients (61%) who had neutropenia, defined as &lt;1,500/microliter; in 16 of these (9%) neutropenia was an isolated finding. Among the 178 patients, 137 (47%) had neutrophil counts below 1,000, and 86 (30%) below 500. Patients with neutropenia following recent chemotherapy were excluded. The risk of clinically relevant bacterial infections after transplantation was significantly increased in patients with neutropenia (p=0.001). Neutropenic patients had an increased risk for infections with gram-positive (relative risk [RR] 1.77, p=0.02), but not gram negative bacteria (RR 1.33, p=0.53). Specific organisms for which the RR was significantly increased included coagulase negative Staphylococcus, Bacillus species and Corynebacterium spp., suggesting that at least part of this risk was associated with intravascular catheters. The RR for invasive fungal infections (Candida and Aspergillus spp.) was 2.56 (p=0.03) for patients with &lt;1,500 neutrophils. The hazard rate (HR) for non-relapse mortality by day 100 (21%) was 1.8 (p=0.03), and by 5 years (42%) was 1.62 (p=0.01). The most frequent causes of death were infections. The HR for 5-year mortality was 1.55 (p=0.007) for neutropenic patients. The pattern for the small group of patients with isolated neutropenia was identical to that for all patients with neutropenia. Pre-transplant neutropenia had no significant impact on engraftment or graft-versus-host disease. The probability of survival did not differ significantly between patients with IPSS scores of 0 and 0.5 with isolated or multiple cytopenias. In summary, only few patients with MDS who undergo transplantation have isolated neutropenia. However, pre-transplant neutropenia in patients with MDS is associated with a significantly increased risk of posttransplant bacterial infections, fungal infections, and non-relapse mortality, and a decreased probability of survival after myeloablative transplantation. A correlation with pre-transplantation colonization remains to be determined. Intensified and possibly extended antibiotic coverage should be considered.

Quantification by Superconducting Quantum Interference Device (SQUID) of Iron Overload after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2134-2134
Author(s):  
Alessandro Busca ◽  
Michele Falda ◽  
Paola Manzini ◽  
Sergio D’antico ◽  
Franco Locatelli ◽  
...  
Keyword(s):  
Risk Factor ◽  
Iron Overload ◽  
Median Time ◽  
Serum Ferritin ◽  
Fungal Infections ◽  
Ferritin Level ◽  
Unrelated Donor ◽  
Iron Depletion ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Introduction. Iron overload (IO) is an adverse prognostic factor in patients who undergo allogeneic HSCT for thalassemia and appears to play a similar role in patients with other hematological disorders. Estimation of IO is primarily based on serum ferritin, however many confounding factors particularly in HSCT recipients may result in frequent ferritin overestimation. Aim of the study was to quantify IO by SQUID after HSCT and evaluate the impact on hepatic function and infections. Additionally, the feasibility of iron-depletion has been investigated. Methods. Between December 2005 and December 2007, 102 consecutive pts who were admitted at our outpatient department have been analyzed. Patients received HSCT from a matched sibling (n=66), a partially matched relative (n=4) or a matched unrelated donor (n=32). Primary diagnosis included acute leukemia/MDS in 61% of cases. Assessment of IO after HSCT included serum ferritin and in those with hyperferritinemia (&gt; 1000 ng/ml), liver iron concentration (LIC) was evaluated by SQUID magnetic susceptometry. Iron removal therapy was offered to patients with moderate (LIC 1000–2000 microg/gww) or severe (LIC &gt;2000 microg/gww) IO. Results. Patients who were in complete remission underwent ferritin assessment at a median time of 578 days from transplantation. Fifty-seven had a ferritin level below the threshold of 1000 ng/ml; in this cohort the median time from HSCT to ferritin assessment was 1006 days, significantly different from the median time of 183 days of the 45 patients who had a ferritin level &gt; 1000 ng/ml. LIC evaluated by SQUID was available for 42/45 patients with elevated ferritin values. Overall, 29 patients had moderate to severe IO: median LIC values were 1493 microg/gww (range 1030–3253 microg/gww). Thirteen patients had normal LIC values (LIC&lt;400 microg/gww) despite high serum ferritin levels. Multivariate analysis showed a significant correlation between ferritin levels &gt; 1000 ng/ml and the occurrence of liver dysfunction defined by the presence of at least one abnormal liver function test (LFT) on two or more occasions (OR 6.8; 95%CI 2.2–20.6); the correlation hold the statistical significance even including into the multivariate model the different time of ferritin assessment. In addition, the rate of proven/probable invasive fungal disease was significantly higher among patients with hyperferritinemia as compared to patients with normal ferritin levels (13% vs 0%; p=.006). Nineteen of the 23 patients considered eligible to iron depletion, underwent regular phlebotomy: 9 patients completed the program after a median time of 10 months (range 3–13 months), reaching the target of ferritin &lt; 500 ng/ml; for 6 patients the program is still ongoing, while 4 patients discontinued the phlebotomy protocol (relapse n=2; hypotension, n=1; progressive anemia, n=1). In 8/9 patients who were revaluated by SQUID at the end of iron depletion program there was a significant decrease of LIC (median 1368 microg/gww to 606 microg/gww; p=.005) that parallels changes of serum ferritin; one patient did not show e remarkable reduction of LIC despite serum ferritin normalization.. Three of the 4 patients ineligible to phlebotomy were successfully treated with deferasirox and 1 patient was treated with deferoxamine. Conclusion. The measurement of LIC obtained by SQUID documented the presence of moderate/severe IO in 69% of the patients with high ferritin levels. Our preliminary data showed that in HSCT recipients, high ferritin level is an independent risk factor for the occurrence of abnormal LFTs and IO may be considered a potential risk factor for fungal infections. A phlebotomy program resulted feasible in 65% of the patients who might benefit from a procedure of iron depletion

scholarly journals Impact of Previous Invasive Fungal Infections on the Outcome of Patients Undergoing Allogeneic Hematopoietic Stem Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5748-5748
Author(s):  
Gaetano Maffongelli ◽  
Gaetano Maffongelli ◽  
Gaetano Maffongelli ◽  
Laura Cudillo ◽  
Fabio Di Piazza ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Conditioning Regimen ◽  
P Value ◽  
Period Range ◽  
European Organization ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Post Transplant ◽  
The Impact

Abstract Introduction: Outcome in allogeneic HSCT varies widely depending on disease type, stage, stem cell source, HLA-matched status and conditioning regimen. IFI is a possible complication of HSCT and a prior IFI increases the patient's risk for transplant related mortality due to the possibility of reactivation of the fungal infection. This study aimed to evaluate the impact of a previous IFI history on transplant outcome Methods: We retrospectively collected the clinical data of patients considered eligible for allogeneic HSCT during 2014 at the Rome Transplant Network (RTN), a JACIE accredited metropolitan transplant program established in Rome since 2006. The observation of patients was continued until 31 December 2015. The diagnosis of IFI were defined as possible, probable and proven as established by European Organization for Research and treatment of Cancer. Results: Twenty-one (37%) out of 57 eligible patients had an IFI episode before transplant: 6 of the episodes were proven, 4 probable and 11 possible. Overall, 10 (47%) pneumonia, 4 (19%) gastroenteritis, 3 sinusitis, 2 candida sepsis, 1 meningitis and 1 cutaneous abscess were registered. Five out of 21 patients (23%) died before HSCT versus 2 of 36 patients (5%) without previous documented IFI, [OR 5.31 95% CI 0.93- 30.40 , p value 0.06 Fisher Test], . A larger percentage of patients with past IFI waited HSCT over 6 months from the date of eligibility in comparison with those without previous IFI [43% vs 30% ; OR 1.87 95% CI 0.54-6.40 , p value 0.5 Yates test]; Sixteen (57%) out of 28 dead patients in the pre-transplant period have had a previous IFI episode vs 5(17%) out of patients alive [OR 6.4, 95% CI 1.89-21.68, p value: 0.004 Yates Test]. In the post-transplant period, only 6% of patients with a past IFI, experienced an engraftment in a time of < 15 days, vs 30% of patients without past IFI [OR 4.86 CI 95% 0,5-43,2, p value 0,2 Yates test]. In the post-transplant period, a IFI was diagnosed in 13 (26%) patients; ten (76%) out of 13 patients had a past IFI versus 9 (24%) of the patients without IFI.. [OR 7.87, CI 95% 1,8-34,2, p value 0,005 Yates test].Among the dead HSCT patients, those who had a previous IFI had a lower median survival [160 days (range 22- 480)] compared to patients without a previous IFI who died [196.5 days period (range 20-820)]. Conclusions: A previous IFI episode in the pre transplant period slow the accessibility to the transplant, adversely affects the engraftment, and is significantly associated with increased post-transplant mortality Disclosures No relevant conflicts of interest to declare.

scholarly journals Community-acquired and hospital-acquired respiratory tract infection and bloodstream infection in patients hospitalized with COVID-19 pneumonia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Kirstine K. Søgaard ◽  
Veronika Baettig ◽  
Michael Osthoff ◽  
Stephan Marsch ◽  
Karoline Leuzinger ◽  
...  
Keyword(s):  
Intensive Care ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Bloodstream Infection ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Icu Patients ◽  
Hospital Acquired Infections ◽  
Hospital Acquired

Abstract Objectives SARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce. Methods We identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for < 24 h (n = 17). We evaluated the frequency of community- and hospital-acquired infections using respiratory and blood culture materials with antigen, culture-based, and molecular diagnostics. For ICU patients, all clinical and microbial findings were re-evaluated interdisciplinary (intensive care, infectious disease, and clinical microbiology), and agreement reached to classify patients with infections. Results In the final cohort of 162 hospitalized patients (median age 64.4 years (IQR, 50.4–74.2); 61.1% male), 41 (25.3%) patients were admitted to the intensive care unit, 34/41 (82.9%) required mechanical ventilation, and 17 (10.5%) of all hospitalized patients died. In total, 31 infections were diagnosed including five viral co-infections, 24 bacterial infections, and three fungal infections (ventilator-associated pneumonia, n = 5; tracheobronchitis, n = 13; pneumonia, n = 1; and bloodstream infection, n = 6). Median time to respiratory tract infection was 12.5 days (IQR, 8–18) and time to bloodstream infection 14 days (IQR, 6–30). Hospital-acquired bacterial and fungal infections were more frequent among ICU patients than other patients (36.6% vs. 1.7%). Antibiotic or antifungal treatment was administered in 71 (43.8%) patients. Conclusions Community-acquired viral and bacterial infections were rare among COVID-19 pneumonia patients. By contrast, hospital-acquired bacterial or fungal infections were frequently complicating the course among ICU patients.

scholarly journals The impact of postoperative percent change of parathormone level from baseline value on the rate of hypocalcemia after total thyroidectomy

2017 ◽  
Author(s):  
Ismail Cem Sormaz ◽  
Ahmet Yalin Iscan ◽  
Ilker Ozgur ◽  
Seyma Karakus ◽  
Fatih Tunca ◽  
...  
Keyword(s):  
Total Thyroidectomy ◽  
Albumin Concentration ◽  
Postoperative Hypocalcemia ◽  
Percent Change ◽  
Number Of Patients ◽  
Increased Risk ◽  
Symptomatic Hypocalcemia ◽  
Postoperative Serum ◽  
Group 2 ◽  
The Impact

Background: To investigate the impact of the percent change of postoperative parathormone (PoPTH) level from baseline value (∆PTH) on the rate of hypocalcemia after total thyroidectomy. Methods: Assays of serum PTH and calcium (Ca) were performed preoperatively and at 24 hours postoperatively in 222 consecutive patients who underwent total thyroidectomy. Postoperative hypocalcemia was defined as serum calcium level corrected for albumin concentration (cCa) &lt;8.5mg/dl. Patients with postoperative hypocalcemia were classified as group1 (n=100) and those with normal Ca levels as group 2 (n=122). The PoPTH levels and ∆PTH were compared between the two groups. ROC analysis was performed to determine the cut off values for PoPTH and ∆PTH. Results: The mean PoPTH level was significantly lower in group 1 compared to group 2 (18.6±15.3 pg/ml vs 32.3±15.6 pg/ml, respectively; P&lt;0.0001). PoPTH values were within normal range in 54% of the patients with hypocalcemia and 35% of those with symptomatic hypocalcemia. PoPTH &lt;28pg/ml or ∆PTH &gt;45 were significantly associated with increased risk of post-thyroidectomy hypocalcemia (P=0.0001). A ∆PTH &gt;70% ,PoPTH ≤ 15.5pg/ml and postoperative serum cCa concentrations&lt;8.0mg/dl significantly predicted symptomatic hypocalcemia(P=0.009;P=0.006;andP=0.0001;respevtively).The sensitivities of ∆PTH,PoPTH level and postoperative serum cCa concentration to predict symptomatic hypocalcemia were 67%,64% and100, respectively. Conclusion: Although, PTH decline significantly correlate with symptomatic hypocalcemia, a considerable number of patients may experience hypocalcemic symptoms in spite of normal PoPTH levels. Analysis of serum Ca concentrations at 24 hours postoperatively help to achieve a more precise prediction of patients who bear a high risk for developing hypocalcemic symptoms.

scholarly journals Molecular Analysis of Diamond Blackfan Anemia and Genotype-Phenotype Correlation: Experience from the Canadian Inherited Marrow Failure Registry

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3621-3621
Author(s):  
Omri Avraham Arbiv ◽  
Bozana Zlateska ◽  
Robert J. Klaassen ◽  
Conrad Fernandez ◽  
Rochelle Yanofsky ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Research Funding ◽  
Gene Panel ◽  
Ribosomal Protein Genes ◽  
Severe Phenotype ◽  
Hematopoietic Stem ◽  
Diamond Blackfan Anemia ◽  
Genetic Groups ◽  
Number Of Patients ◽  
The Impact

Abstract Background/Objectives: Diamond Blackfan anemia (DBA) is an inherited disorder characterized by chronic hypoproductive anemia, physical malformations, and an increased risk of malignancies. At least 12 DBA genes have been identified, which include various ribosomal protein genes and the transcription factor GATA1. The aims of our study were (1) to identify the mutation spectrum of DBA patients, utilizing a cohort of patients enrolled on the Canadian Inherited Marrow Failure Registry (CIMFR) and (2) to determine whether specific hematological abnormalities, malformations, and outcomes are associated with specific mutations. Methods: Patients were enrolled on the CIMFR, which is a multicenter cohort study of inherited bone marrow failure syndromes (IBMFS). Genetic testing was performed using one or more of the following tests: Sanger sequencing, next generation sequencing (NGS) DBA gene panel, a comprehensive NGS IBMFS gene panel developed in our laboratory, or comparative genetic hybridization (CGH). Severity of the hematological disease was dichotomized according to a patient's requirement for chronic treatment: those who were maintained on corticosteroids, blood transfusions, or received a hematopoietic stem cell transplantation were considered to have a more severe phenotype than those who did not require hematological treatment. Chi-square tests with a Fisher's exact test correction were used to compare genetic groups with at least 5 patients on observed phenotypes. Results: 71 patients with DBA have been enrolled in our registry. A causal mutation has been identified in 36 of these patients, with the following rates: RPS19 (n=11), RPL11 (n=7), RPL5 (n=6), RPS26 (n=5), RPL35a (n=2), RPS24 (n=2), and one of each RPS7, RPS29, RPS17. Remarkably, a substantial number of patients in our population-based cohort (19.4%) had mild hematological phenotype requiring no therapy. Patients with RPL11 mutations tended to have a less severe DBA phenotype, while patients with RPS19 mutations tended to have a more severe phenotype (p=0.04). In terms of non-hematological malformations, we found no differences in cardiac, stature and craniofacial malformations across the groups compared (all p>0.1). However, patients with RPL5 mutations had significantly more hand malformations (p=0.02), and patients with RPS26 mutations had more genitourinary malformations (p=0.04). To control for the impact of mutation severity on the observed phenotype, we compared the prevalence of mutations that are predicted to result in truncated or lack of protein from the respective allele (large copy-number variation, nonsense, or indel frameshift) to mutations that are predicted to be hypomorphic or affect function (splicing, indel/inframe and, missense) between mutation categories. There were no differences among genetic groups in the severity of their mutations (p=0.58). Conclusions: Mutations in a wide spectrum of ribosomal protein genes underlie DBA cases in Canada, which approximate those observed by other registries in Western countries. Patients with DBA caused by RPL11 mutations tended to have a milder hematological phenotype, while patients with RPS19 mutation tended to have a more severe phenotype. Mutations in RPS26 and RPL5 are associated with genitourinary and hand malformations, respectively. Our findings may help improve counseling of DBA patients and their family. Future studies are needed to replicate our results and determine whether these findings can help personalize care. Disclosures Lipton: Ariad: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding.

scholarly journals Impact of Different T Cell Depletion Protocols on Immune Reconstitution Following Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 43-44
Author(s):  
Amandine Pradier ◽  
Adrien Petitpas ◽  
Anne-Claire Mamez ◽  
Federica Giannotti ◽  
Sarah Morin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Reconstitution ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
T Cell Depletion ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
The Impact

Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic modality for a variety of hematological malignancies and congenital disorders. One of the major complications of the procedure is graft-versus-host-disease (GVHD) initiated by T cells co-administered with the graft. Removal of donor T cells from the graft is a widely employed and effective strategy to prevent GVHD, although its impact on post-transplant immune reconstitution might significantly affect anti-tumor and anti-infectious responses. Several approaches of T cell depletion (TCD) exist, including in vivo depletion using anti-thymocyte globulin (ATG) and/or post-transplant cyclophosphamide (PTCy) as well as in vitro manipulation of the graft. In this work, we analyzed the impact of different T cell depletion strategies on immune reconstitution after allogeneic HSCT. Methods We retrospectively analysed data from 168 patients transplanted between 2015 and 2019 at Geneva University Hospitals. In our center, several methods for TCD are being used, alone or in combination: 1) In vivo T cell depletion using ATG (ATG-Thymoglobulin 7.5 mg/kg or ATG-Fresenius 25 mg/kg); 2) in vitro partial T cell depletion (pTCD) of the graft obtained through in vitro incubation with alemtuzumab (Campath [Genzyme Corporation, Cambridge, MA]), washed before infusion and administered at day 0, followed on day +1 by an add-back of unmanipulated grafts containing about 100 × 106/kg donor T cells. The procedure is followed by donor lymphocyte infusions at incremental doses starting with 1 × 106 CD3/kg at 3 months to all patients who had received pTCD grafts with RIC in the absence of GVHD; 3) post-transplant cyclophosphamide (PTCy; 50 mg/kg) on days 3 and 4 post-HSCT. Absolute counts of CD3, CD4, CD8, CD19 and NK cells measured by flow cytometry during the first year after allogeneic HSCT were analyzed. Measures obtained from patients with mixed donor chimerism or after therapeutic DLI were excluded from the analysis. Cell numbers during time were compared using mixed-effects linear models depending on the TCD. Multivariable analysis was performed taking into account the impact of clinical factors differing between patients groups (patient's age, donor type and conditioning). Results ATG was administered to 77 (46%) patients, 15 (9%) patients received a pTCD graft and 26 (15%) patients received a combination of both ATG and pTCD graft. 24 (14%) patients were treated with PTCy and 26 (15%) patients received a T replete graft. 60% of patients had a reduced intensity conditioning (RIC). 48 (29%) patients received grafts from a sibling identical donor, 94 (56%) from a matched unrelated donor, 13 (8%) from mismatched unrelated donor and 13 (8%) received haploidentical grafts. TCD protocols had no significant impact on CD3 or CD8 T cell reconstitution during the first year post-HSCT (Figure 1). Conversely, CD4 T cells recovery was affected by the ATG/pTCD combination (coefficient ± SE: -67±28, p=0.019) when compared to the T cell replete group (Figure 1). Analysis of data censored for acute or chronic GVHD requiring treatment or relapse revealed a delay of CD4 T cell reconstitution in the ATG and/or pTCD treated groups on (ATG:-79±27, p=0.004; pTCD:-100±43, p=0.022; ATG/pTCD:-110±33, p&lt;0.001). Interestingly, pTCD alone or in combination with ATG resulted in a better reconstitution of NK cells compared to T replete group (pTCD: 152±45, p&lt;0.001; ATG/pTCD: 94±36, p=0.009; Figure 1). A similar effect of pTCD was also observed for B cells (pTCD: 170±48, p&lt;.001; ATG/pTCD: 127±38, p&lt;.001). The effect of pTCD on NK was confirmed when data were censored for GVHD and relapse (pTCD: 132±60, p=0.028; ATG/pTCD: 106±47, p=0.023) while only ATG/pTCD retained a significant impact on B cells (102±49, p=0.037). The use of PTCy did not affect T, NK or B cell reconstitution when compared to the T cell replete group. Conclusion Our results indicate that all TCD protocols with the only exception of PTCy are associated with a delayed recovery of CD4 T cells whereas pTCD of the graft, alone or in combination with ATG, significantly improves NK and B cell reconstitution. Figure 1 Disclosures No relevant conflicts of interest to declare.

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