Meta-analysis of clinical risk factors of patients with systemic lupus erythematosus complicated with invasive fungal infection.

BACKGROUND: To systematically evaluate the clinical risk factors of patients with systemic lupus erythematosus (SLE) complicated with invasive fungal infection (IFI) among patients. METHODS: A meta-analysis was performed of all the literatures germane to estimate the clinical risk factors of patients with SLE complicated with IFI from published clinical trials from 1990 to April 2022. Mean differences, odds ratio and 95% confidence intervals were calculated, and the meta-analysis was conducted with Stata 12.0 software (StataCorp, College Station, TX). RESULTS: A total of 14 clinical research involving 1129 patients were included. The results of meta-analysis demonstrated that immunosuppressant, glucocorticoids, systemic lupus erythematosus disease activity index score, antibiotic were risk factors associated with IFI in SLE patients. However, age, sex, course of disease, leukopenia, lymphopenia, C- reactive protein and hypoproteinemia were not the risk factors associated with IFI in patients with SLE. CONCLUSION: Our results indicate that immunosuppressant, glucocorticoids, systemic lupus erythematosus disease activity index score, antibiotic were risk factors for IFI in SLE patients. However, high quality of multicenter, large sample size-controlled trials are needed to validate the result.

Single-Nucleotide Polymorphisms, c.415C > T (Arg139Cys) and c.416G > A (Arg139His), in the NUDT15 Gene Are Associated with Thiopurine-Induced Leukopenia.

While nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene polymorphism Arg139Cys (rs116855232) is known to be a risk factor for thiopurine-induced severe leukopenia, association with the NUDT15 gene polymorphism Arg139His (rs147390019) has not yet been clarified. In addition, the accuracy of TaqMan PCR to assess these two polymorphisms has not been investigated. In this study, we evaluated TaqMan PCR for detection of the NUDT15 single-nucleotide polymorphisms (SNPs) and examined the clinical impact of Arg139His on thiopurine-induced leukopenia. First, we demonstrated that a TaqMan PCR assay successfully detected the Arg139His polymorphism of NUDT15 in clinical samples. Next, the NUDT15 gene polymorphisms (Arg139Cys and Arg139His) were separately analyzed by TaqMan Real-Time PCR in 189 patients from August 2018 to July 2019. The incidences of leukopenia within 2 years were 16.2, 57.9, and 100% for arginine (Arg)/Arg, Arg/cysteine (Cys), and Arg/histidine (His), respectively. The leukopenia was significantly increased in Arg/Cys and Arg/His compared with Arg/Arg. This retrospective clinical study indicated that, in addition to Arg139Cys, Arg139His may be clinically associated with a high risk of leukopenia. Pharmacogenomics will help in selecting drugs and determining the individualized dosage of thiopurine drugs.

Safety and efficacy of PD-1 and PD-L1 inhibitors in relapsed and refractory Hodgkin's lymphoma: a systematic review and meta-analysis of 20 prospective studies.

BACKGROUND: Inhibitors of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have been used in the treatment of relapsed and refractory Hodgkin's lymphoma (R/R HL) recently. To further understand the safety and efficacy of PD-1/PD-L1 inhibitors in R/R HL, we conducted this meta-analysis. METHODS: Databases and the Clinical Registration Platforms have been systematically searched for related studies by March 2022. For safety analysis, the incidence and exhibition of any grade and grade 3 or higher adverse effects (AEs) were evaluated. Besides, severe AEs (SAEs), treatment-related deaths, and AEs leading to treatment discontinuation were summarized. The overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, progression-free survival (PFS), overall survival (OS), and duration of response (DOR) were calculated for efficacy analysis. All processes were implemented mainly through the package Meta and MetaSurv of software R 4.1.2. RESULTS: Overall 20 studies and 1440 patients were enrolled. The pooled incidence of any grade and grade 3 or higher AEs were 92% and 26%, respectively. The pooled ORR, CR rate and PR rate were 79%, 44% and 34%, respectively. The most common AEs were neuropathy (29%), nausea (27%), pyrexia (26%), and leukopenia (25%), and the most common grade 3 or higher AEs included leukopenia (10%), infusion reaction (8%), weight gain (3%), and neutropenia (2.7%). In survival analysis, pembrolizumab monotherapy appeared to perform better compared to nivolumab monotherapy. CONCLUSIONS: PD-1/PD-L1 inhibitors show promising efficacy and tolerable AEs in the treatment of R/R HL.

The need for evolution in the management of febrile neutropenia in pediatric cancer: TRIIO KIDS update

New treatments have increased the life expectancy of pediatric patients diagnosed with malignant hematological diseases, often at the cost of protracting their immunocompromised state in the form of prolonged neutropenia. This neutropenic state favors the development of bacterial and fungal infections. Moreover, recent years have seen a series of changes in the epidemiology of fungal and Clostridium infections. These changes necessitate adaptations to the management of pediatric patients with febrile neutropenia, who are at risk of further increases in already high rates of morbidity and mortality. This article discusses the current bases for the management of febrile neutropenia and associated emerging fungal infections, as well as the epidemiology, diagnosis, and treatment of Clostridioides difficile in pediatric patients diagnosed with malignant hematological diseases (AU)

[Clinical characteristics of 37 antiphospholipid syndrome patients complicated by autoimmune hemolytic anemia].

Objective: We sought to investigate the clinical characteristics and risk factors of antiphospholipid syndrome (APS) complicated by autoimmune hemolytic anemia (AIHA). Methods: Retrospective anaysis.Three hundred fifteen consecutive patients with APS were enrolled at the Department of Rheumatology of Peking Union Medical College Hospital between May 2017 to May 2021, and their clinical manifestations[including initial symptoms, time interval between APS onset and diagnosis, systemic lupus erythematosus(SLE), thrombotic events, obstetric morbidity, and extra-criteria manifestations] and laboratory test results[including blood routine, antiphospholipid antibodies(aPLs), blood lipid profile, homocysteine, anti-nuclear antibody profile, immunoglobulin levels, and complement levels] were collected. Then, univariate and multivariate logistic regression analyses were performed. Clinical features and risk factors were analyzed using univariable and multivariable logistic regression analysis. Results: Among 315 APS patients, 37 cases (11.7%) were complicated by AIHA, and AIHA was the first manifestation or co-occurrence. The median time interval between APS onset and diagnosis was 12 months. The proportion of SLE in APS patients combined with AIHA was higher than that in APS patients without AIHA[62.2%(23/37) vs. 19.4%(54/278), P<0.001]. There was no significant difference in the proportions of thrombosis and pregnancy morbidity between the two groups. In terms of extra-criteria manifestations, APS patients with AIHA had a significantly (P<0.05) greater risk of thrombocytopenia (OR=6.19, 95%CI 2.81-13.65) and higher proportions of hypocomplementemia, a positive lupus anticoagulant (LA) result, double aPLs positivity[i.e., any two of the following antibodies were positive: LA, anticardilolipin antibody(aCL), and anti-ß2 glycoprotein Ⅰ(ß2GPⅠ)], and triple aPLs positivity (i.e., LA, aCL, and anti-ß2GPⅠ antibodies were all positive). Multivariate logistic regression analysis showed that SLE (OR=3.46,95%CI 1.60-7.48), thrombocytopenia (OR=2.56,95%CI 1.15-5.67), and hypocomplementemia (OR=4.29,95%CI 2.03-9.04) were independent risk factors for the complication of APS. In the primary APS subgroup, multivariate logistic regression analysis showed that livedo reticularis (OR=10.51,95%CI 1.06-103.78), thrombocytopenia (OR=3.77, 95%CI 1.23-11.57), and hypocomplementemia (OR=5.92,95%CI 1.95-17.95) were independent risk factors for the complication of APS. Conclusions: AIHA is not rare in APS patients; moreover, it occurs more frequently in APS secondary to SLE and is more likely to present with a variety of extra-criteria manifestations. Patients with AIHA should be promptly tested for antiphospholipid antibody profiles and alerted to the possibility of thrombotic events.

Complicated multi-drug resistant typhoid fever with cerebral oedema, diffuse encephalitis and fungal infection of the oral cavity: A case report.

Enteric fever is a highly fatal infectious disease that can present with extensive symptoms that renders diagnosis quite risky. Multi-drug resistant Salmonella typhi infection has become endemic in third world countries and has been routinely associated with catastrophic complications and even death, with diagnostic and therapeutic impedance. Typhoid fever is known to cause life-threatening cerebral complications. We report the case of a 16-year-old male who presented to us with a high-grade fever, watery diarrhoea, altered level of consciousness, and a mixed dark-coloured crusted oral lesion. Blood workup showed neutropenia, lymphocytopenia, thrombocytopenia, transaminitis, and hyponatraemia. Blood culture grew multi-drug resistant Salmonella Typhi. CT scan of the brain showed diffuse cerebral oedema, while EEG was consistent with the diagnosis of diffuse encephalitis. The patient responded well to culture-sensitive antibiotics, while the oral lesion showed a dramatic response to presumptive antifungal treatment. We discuss the compositions available to date on typhoid-associated encephalitis and the connection of fungal infection in this specific case attempting to promote awareness regarding possible unorthodox presentations of enteric fever.

[Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy].

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Treatment of Infants and Children With SARS-CoV-2 Monoclonal Antibodies: A European Case Series.

BACKGROUND: Although severe COVID-19 in children is rare, those with certain pre-existing health conditions are more prone to severe disease. Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are potent antiviral agents that reduce adverse clinical outcomes in adults, but are commonly not approved for use in pediatric patients. METHODS: We retrospectively evaluated mAb treatment in children <12 years of age or <40kg with SARS-CoV-2 infection between January 1, 2021, and March 7, 2022, in 12 tertiary care centers in 3 European countries. RESULTS: We received data from 53 patients from Austria, Denmark and Germany. Median age was 5.4 years [0-13.8, interquartile range (IQR) = 6.2], and median body weight was 20 kg (3-50.1, IQR = 13). The most frequent SARS-CoV-2 variant in this study, if known, was Omicron, followed by Delta and Alpha. Pre-existing conditions included immunodeficiency, malignancy, hematologic disease, cardiac disease, chronic lung disease, chronic liver disease, kidney disease and diabetes. Forty-two patients received sotrovimab (79%), 9 casirivimab/imdevimab (17%) and 2 bamlanivimab (4%). All but 1 patient survived. Median duration of hospital stay was 3 days (0-56, IQR = 6). Seven patients required treatment in an intensive care unit, and 5 required high-flow nasal cannula treatment. Potential side effects included neutropenia (6/53, 11%), lymphopenia (3/53, 6%), nausea or vomiting (2/53, 4%), rise of alanine transaminase (1/53, 2%) and hypotonia (1/53, 2%). CONCLUSIONS: MAb treatment was well tolerated by children in this cohort.

Relationship between the EULAR/ACR classification criteria and organ damage in systemic lupus erythematosus.

OBJECTIVES: To study the relationship between the 2019 EULAR/ACR classification criteria and organ damage in patients with systemic lupus erythematosus (SLE). METHODS: Patients involved in a cross-sectional validation study of the EULAR/ACR criteria and judged by a panel of rheumatologists to be clinical SLE were studied. Those who fulfilled the EULAR/ACR criteria at their last clinic visit were stratified into 2 groups based on a cutoff score of 20. The last SLE International Collaborating Clinic (SLICC) Organ Damage Index (SDI) was compared between these two groups. Relationship among the domains of the EULAR/ACR criteria and SDI in all patients was studied by using Spearman's rank correlation. RESULTS: A total of 562 SLE patients were studied (93.6% women; age 36.5 ± 14.1 years; follow-up duration 11.6 ± 6.6 years). The mean and median EULAR/ACR criteria scores in those who fulfilled the EULAR/ACR criteria (N = 542) were 24.6 ± 7.3 and 24 (interquartile range 19-30), respectively. A total of 392 patients had EULAR/ACR scores of ≥20 (group 1), and 150 patients had scores of 10-19 (group 2). Group 1 patients had significantly higher prevalence of fever, alopecia, oral ulcers, acute lupus skin lesions, arthritis, serositis, seizure, hemolytic anemia, leukopenia, and renal disease and so were the anti-dsDNA, anti-Sm, antiphospholipid antibodies, and low complement state. Organ damage (SDI score of ≥1) occurred in 232 (42.8%) patients. Patients in group 1 had significantly higher SDI scores in the renal, cardiovascular, dermatological, and gonadal domains than group 2. The renal, neuropsychiatric, and antiphospholipid antibody domain scores of the EULAR/ACR criteria correlated positively with the total SDI. The renal domain of the EULAR/ACR criteria had the strongest correlation with renal damage (Rho 0.30; p < 0.001). Patients who scored 10 points in the renal domain had significantly higher renal damage score than those scored 8 points or 4 points. Gonadal damage score was also significantly more common in the 10-point than in the 8-point group. CONCLUSION: In addition to disease classification, the EULAR/ACR SLE criteria may have value in predicting prognosis.

Treatment of Infants and Children With SARS-CoV-2 Monoclonal Antibodies: A European Case Series.

BACKGROUND: Although severe COVID-19 in children is rare, those with certain pre-existing health conditions are more prone to severe disease. Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are potent antiviral agents that reduce adverse clinical outcomes in adults, but are commonly not approved for use in pediatric patients. METHODS: We retrospectively evaluated mAb treatment in children <12 years of age or <40kg with SARS-CoV-2 infection between January 1, 2021, and March 7, 2022, in 12 tertiary care centers in 3 European countries. RESULTS: We received data from 53 patients from Austria, Denmark and Germany. Median age was 5.4 years [0-13.8, interquartile range (IQR) = 6.2], and median body weight was 20 kg (3-50.1, IQR = 13). The most frequent SARS-CoV-2 variant in this study, if known, was Omicron, followed by Delta and Alpha. Pre-existing conditions included immunodeficiency, malignancy, hematologic disease, cardiac disease, chronic lung disease, chronic liver disease, kidney disease and diabetes. Forty-two patients received sotrovimab (79%), 9 casirivimab/imdevimab (17%) and 2 bamlanivimab (4%). All but 1 patient survived. Median duration of hospital stay was 3 days (0-56, IQR = 6). Seven patients required treatment in an intensive care unit, and 5 required high-flow nasal cannula treatment. Potential side effects included neutropenia (6/53, 11%), lymphopenia (3/53, 6%), nausea or vomiting (2/53, 4%), rise of alanine transaminase (1/53, 2%) and hypotonia (1/53, 2%). CONCLUSIONS: MAb treatment was well tolerated by children in this cohort.

Serum biochemical changes in cats with naturally acquired feline cytauxzoonosis.

OBJECTIVE: The geographical distribution of feline cytauxzoonosis is expanding in the US. Clinical signs of feline cytauxzoonosis, including lethargy, anorexia, and icterus, are similar to hepatic lipidosis and cholangiohepatitis. Hematologic and serum biochemical abnormality patterns may assist practitioners in prioritizing feline cytauxzoonosis as a differential diagnosis over hepatic lipidosis and cholangiohepatitis. SAMPLE: Hematology and serum biochemical profiles of cats with naturally acquired feline cytauxzoonosis, hepatic lipidosis, or cholangiohepatitis. PROCEDURES: Retrospective search and analysis of the Kansas State Veterinary Diagnostic Laboratory or Kansas State University Veterinary Health Center records between January 2007 and June 2018 for cats with cytauxzoonosis, hepatic lipidosis, or cholangiohepatitis. RESULTS: Patients with acute feline cytauxzoonosis presented with frequent nonregenerative anemia (20/28 [71%]), leukopenia (23/28 [82%]), thrombocytopenia (23/23 [100%]), hyperbilirubinemia (27/28 [97%]), hypoalbuminemia (26/28 [93%]), reduced (18/28 [64%]) or low normal (10/28 [36%]) serum ALP activity, and hyponatremia (23/28 [82%]). Reduced ALP activity was unique to cats with feline cytauxzoonosis relative to hepatic lipidosis and cholangiohepatitis. No correlation between the severity of anemia and the magnitude of hyperbilirubinemia was identified in feline cytauxzoonosis patients. CLINICAL RELEVANCE: The combination of nonregenerative anemia, leukopenia, thrombocytopenia, hyperbilirubinemia, and reduced serum ALP activity in icteric cats may increase the clinical suspicion, but is not pathognomonic, for acute feline cytauxzoonosis. Hematologic and serum biochemical abnormalities of naturally acquired feline cytauxzoonosis are like those reported with feline bacterial sepsis. Blood smear evaluation for intraerythrocytic Cytauxzoon felis piroplasms, tissue aspirates for schizont-laden macrophages, and/or molecular testing are required to diagnose feline cytauxzoonosis.

Epidemiological, clinical and hematological profiles of visceral leishmaniasis among patients visiting Tefera Hailu Memorial Hospital, Northeast Ethiopia: a 4 year retrospective study.

Visceral leishmaniasis is a major, life-threatening parasitic disease that still remains a serious public health problem in Ethiopia. Understanding the epidemiological, clinical, and hematological profiles of visceral leishmaniasis patients is important for implementing evidence-based control strategies. It is also important for early treatment and to decrease the mortality rate from the disease. Therefore, this study was aimed at assessing the epidemiological, clinical, and hematological profiles of visceral leishmaniasis among patients visiting Tefera Hailu Memorial Hospital, Northeast Ethiopia. A retrospective study was conducted at Tefera Hailu Memorial Hospital from September 2017 to August 2021. Data were collected from the medical records of suspected patients who were tested by the rK39 rapid diagnostic by strictly following standard operating procedures. The data was summarized using Microsoft Excel and analyzed using SPSS 26 version software. Descriptive statistics were used to describe the epidemiological, clinical, and hematological profiles of visceral leishmaniasis patients. A p-value < 0.05 was considered statistically significant. The overall positivity rate for visceral leishmaniasis was 23.4% (132/564). The result of this study indicated a fluctuating yet declining trend in VL over the past 4 years. From a total of 132 VL confirmed cases, the numbers of cases were highest among males (78.0%), those 15-29 years of age (37.1%), and urban residents (89.4%). Furthermore, Abergele (11.0%), Sehala (6.0%), and Ziquala (5.0%) districts had the highest number of VL cases. The major clinical presentations of patients were fever (96.2%), splenomegaly (94.7%), and general weakness (80.3%). With regard to hematological profiles, the most common findings were anemia (86.4%), thrombocytopenia (81.8%), leucopenia (78.8%), neutropenia (74.2%), and pancytopenia (71.2%). In the study area, the VL positivity rate was high. Our findings also concluded that VL causes significant alterations in clinical and hematological parameters. Therefore, the zone health office and other concerned stakeholders should strengthen evidence-based control programs for VL.

Pediatric autoimmune myelofibrosis: Experience from a large pediatric tertiary care center.

Autoimmune myelofibrosis (AIMF) is a rare disorder characterized by cytopenias and autoimmunity, with characteristic bone marrow findings that include lymphocytic infiltration and fibrosis. AIMF is described predominantly in adult populations who have systemic lupus erythematosis (SLE), with scant pediatric cases described mainly in older adolescents with SLE. Here, we described the largest single-center pediatric experience of pediatric autoimmune myelofibrosis (PAIMF) series, demonstrating both similarities and distinctions from the adult experience. Patients overall respond well to steroid therapy, but these patients were significantly younger, infrequently carried a diagnosis of SLE, and causative genetic lesions were identified in many cases.

Outcomes of Patients with Thrombocytopenia Evaluated at Hematology Subspecialty Clinics.

BACKGROUND: Thrombocytopenia is a frequently encountered laboratory abnormality and a common reason for hematology referrals. Workup for thrombocytopenia is not standardized and frequently does not follow an evidence-based algorithm. We conducted a systematic analysis to evaluate the laboratory testing and outcomes of patients evaluated for thrombocytopenia at hematology clinics in a tertiary referral center between 2013 and 2016. PATIENT AND METHODS: We performed a comprehensive chart review for patients evaluated for thrombocytopenia during the study period. Patients were followed for 1 year from the initial hematology evaluation and assessed for the development of a hematologic malignancy, rheumatologic, or infectious diseases among other clinical outcomes. RESULTS: We evaluated 472 patients with a median (range) age of 61 (17-94) years. The majority (63.8%) had mild thrombocytopenia. Within 1 year of follow-up, 14 patients (3.0%) were diagnosed with a hematologic malignancy. A higher likelihood of developing a hematologic malignancy was noted in patients with concurrent leukopenia (hazard ratio [HR] 9.97, 95% confidence interval [CI] 3.28-30.32, p < .01) and increasing age (HR per 10-year deciles 1.52, 95% CI 1.03-2.25, p = .03). In patients with asymptomatic isolated mild thrombocytopenia, laboratory testing did not reveal any significant positive findings and patients did not receive any new major diagnosis during the follow-up period. CONCLUSION: Our findings provide basis and call for development of an evidence-based algorithmic approach for evaluation of patients with thrombocytopenia, testing, and referrals. It also supports a conservative approach mainly driven by physical exam signs, symptoms, and other laboratory findings for patients with isolated mild thrombocytopenia.

Effects of peripheral blood leukocyte count and tumor necrosis factor-alpha on early death in acute promyelocytic leukemia.

BACKGROUND: Early death remains a major factor in survival in APL. We aimed to analyze the risk factors for differentiation syndrome and early death in acute promyelocytic leukemia (APL). METHODS: The clinical data of APL patients who were newly diagnosed at Mianyang Central Hospital from January 2013 to January 2022 were retrospectively analyzed. RESULTS: Eighty-six newly diagnosed APL patients (37 males and 49 females) were included in this study. The median age was 46 (17-75) years. Sixty-one patients (70.9%) had low/intermediate-risk APL, and 25 patients (29.1%) had high-risk APL. The incidence of differentiation syndrome (DS) was 62.4%. The multivariate analysis showed that a peak white blood cell (WBC) count ≥16 × 10^9/L was an independent risk factor (OR = 11.000, 95% CI: 2.830-42.756, P = 0.001) for DS in all APL patients, while a WBC count ≥10 × 10^9/L on Day 5 was an independent risk factor for DS in low-intermediate risk APL patients (OR = 9.114, 95% CI: 2.384-34.849, P = 0.001). There were 31 patients (36.5%) with mild DS and 22 patients (25.9%) with severe DS. The multivariate analysis showed that WBC count ≥23 × 10^9/L at chemotherapy was an independent risk factor for severe DS (OR = 10.500, 95% CI: 2.344-47.034, P = 0.002). The rate of early death (ED) was 24.4% (21/86). The multivariate analysis showed that male gender (OR = 7.578,95% CI:1.136-50.551, P = 0.036), HGB < 65 g/L (OR = 16.271,95% CI:2.012-131.594, P = 0.009) and WBC count ≥7 × 10^9/L on Day 3(OR = 23.359,95% CI:1.825-298.959, P = 0.015) were independent risk factors for ED. The WBC count at diagnosis, WBC count on Day 3 and WBC count on Day 5 had moderate positive correlations with tumor necrosis factor-α (TNF-α) at diagnosis, and the correlation coefficients were 0.648 (P = 0.012), 0.615 (P = 0.033), and 0.609 (P = 0.035), respectively. The WBC count had no correlation with IL-6. CONCLUSION: During induction treatment, cytotoxic chemotherapy may need to be initiated to reduce the risk of DS for APL patients with a low-intermediate risk WBC count ≥10 × 10^9/L on Day 5 or for all patients with a peak WBC count ≥16 × 10^9/L. Patients with WBC > 7 × 10^9/L on Day 3 have a higher risk of ED. Leukocyte proliferation is associated with TNF-α rather than IL-6, and TNF-α may be a potential biomarker for predicting ED.

Effectiveness and safety of switching to teriflunomide in older patients with relapsing multiple sclerosis: A real-world retrospective multicenter analysis.

BACKGROUND: The prevalence of multiple sclerosis (MS) in older people is increasing due to population aging and availability of effective disease-modifying therapies (DMTs). Treating older people with MS is complicated by age-related and MS-related comorbidities, immunologic effects of prior DMTs, and immunosenescence. Teriflunomide is a once-daily oral immunomodulator that has demonstrated efficacy and acceptable safety in clinical trials of adults with relapsing forms of MS (RMS). However, there are limited clinical trial and real-world data regarding teriflunomide use in people with MS aged >55 years. We analyzed real-world data to assess the effectiveness and safety of teriflunomide in older people with RMS who had switched to this agent from other DMTs. METHODS: People with RMS (relapsing remitting and active secondary progressive MS) aged ≥55 years who had switched from other DMTs to teriflunomide (7 mg or 14 mg) for ≥1 year were identified retrospectively by chart review at four sites in the United States. Data were extracted from medical records from 1 year pre-index to 2 years post-index (index defined as the teriflunomide start date). Assessments of effectiveness included annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging (MRI) outcomes. Assessments of safety included lymphocyte counts, infections, and malignancies. We examined the effectiveness outcomes and lymphocyte counts within sub-groups defined by age (55-64, ≥65 years), sex, MS type, and prior route of DMT administration (oral, injectable, infusible). RESULTS: In total, 182 patients with RMS aged ≥55 years who switched from other DMTs to teriflunomide were identified (mean [SD] age: 62.5 [5.4] years). Mean ARR decreased from the start of teriflunomide treatment (mean [SD]: 0.43 [0.61]) to year 1 post-index (0.13 [0.65]) and year 2 post-index (0.05 [0.28]). Mean EDSS score remained unchanged from index (mean [SD]: 4.5 [1.8]) to 1 year post-treatment (4.5 [1.8]) and increased slightly at 2 years post-treatment (4.7 [1.7]). MRI scans from index and years 1 and 2 post-index compared with scans from the previous year indicated that most patients had stable or improved MRI outcomes at index (87.7%) and remained stable or improved at years 1 (96.0%) and 2 (93.6%). Lymphopenia decreased at years 1 (21.4%) and 2 post-index (14.8%, compared to index (23.5%). By 1 year post-index, fewer patients had grade 3 or 4 lymphopenia, and at 2 years post-index, there were no patients with grade 3 or 4 lymphopenia. Infection incidence was low (n = 40, 22.0%) and none were related to teriflunomide. The decreases in lymphopenia were driven by decreases among people who switched from a prior oral DMT; there were no notable differences in lymphopenia across the other sub-groups examined. ARR, EDSS score, and MRI outcomes across all sub-groups were similar to the results of the overall population. CONCLUSION: Our multicenter, longitudinal, retrospective study demonstrated that patients with RMS aged 55 or older switching to teriflunomide from other DMTs had significantly improved ARR, stable disability, and stable or improved MRI over up to 2 years' follow up. Safety results were acceptable with fewer patients exhibiting lymphopenia at years 1 and 2 post-index.

Relapses are common in severe hematologic systemic lupus erythematosus and may be prevented by early institution of immunosuppressive agents: Α real-life single-center study.

BACKGROUND: Hematologic manifestations are common in systemic lupus erythematosus (SLE), either at initial presentation or during the course of the disease, but data regarding their natural history are scarce. OBJECTIVE: To describe the characteristics, treatments, and outcomes of severe hematological manifestations in a large cohort of lupus patients. METHODS: Retrospective cohort study of patients in the "Attikon" lupus cohort who had a history of a severe hematologic manifestation, defined as autoimmune hemolytic anemia (AIHA) with hemoglobin < 8 g/dL, thrombocytopenia with platelet count < 30,000/mm3, Evans syndrome with hemoglobin < 8 g/dL, and/or platelet count < 30,000/mm3, neutropenia with < 500 neutrophils/mm3, thrombotic microangiopathy (TMA)/thrombotic thrombocytopenic purpura (TTP)-like syndrome, or macrophage activation syndrome (MAS). Demographic and clinical characteristics, treatments, and outcomes were recorded. RESULTS: From over 300 patients with hematologic manifestations, 41 qualified as severe (70.7% women, mean [SD] age at SLE diagnosis 42.6 [18.0] years). Hematologic manifestations preceded SLE diagnosis in 13 patients (31.7%), was concomitant to SLE diagnosis in 16 patients (39%), and occurred during the course of the disease in 12 (29.3%) patients, with a mean (SD) disease duration of 8.7 (5.5) years. Thrombocytopenia was the most common severe hematological manifestation (56.1%), followed by AIHA (17.1%) and TTP-like syndrome (12.2%). For initial treatment, all patients were treated with glucocorticoids (GC), while rituximab and cyclophosphamide were the most frequently used immunosuppressive agents. Following initial treatment, relapse occurred in 22 patients (53.7%). Compared to patients that did not relapse, those that relapsed had less often received concomitant immunosuppressive agents following treatment of initial episode (n = 17/23, 73.9% vs 5/17, 29.4%, p = 0.005). CONCLUSION: Severe hematologic disease in SLE has a high risk of relapse, which may be mitigated by the early institution of GC-sparing agents.

Burden of neutropenia and leukopenia among adult kidney transplant recipients: A systematic literature review of observational studies.

BACKGROUND: Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post-KT. METHODS: We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception-June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs. RESULTS: Of 2081 records, 82 studies met inclusion criteria. Seventy-three studies reported the epidemiology of L/N post-KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/µl, ranged from 13% to 48% within 1-year post-transplant; ANC <500/µl ranged from 15% to 20%. Leukopenia, defined as white blood cell counts <3500/µl, was 19% to 83%. Eleven studies reported independent risk factors associated with L/N post-KT. D+/R- cytomegalovirus status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N-associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti-thymoglobulin and the need for granulocyte colony-stimulating factor (G-CSF) use were common with L/N. CONCLUSION: Findings suggest post-transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G-CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post-KT.

Sex differences in systemic lupus erythematosus (SLE): an inception cohort of the Chinese SLE Treatment and Research Group (CSTAR) registry XVII.

BACKGROUND: The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort. METHODS: Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex. RESULTS: In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ±â€Š15.8 years vs. 35.1 ±â€Š13.7 years, P  = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ±â€Š1.13 vs. 0.34 ±â€Š0.81, P  = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P  = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P  = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P  = 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P  = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P  = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P  = 0.002), musculoskeletal damage (P  = 0.023), cardiovascular impairment (P  = 0.009), and CYC use (P  = 0.001); while leukopenia (P  = 0.017), arthritis (P  = 0.014), and mycophenolate usage (P  = 0.013) rates were lower. CONCLUSIONS: Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.

Concurrent definitive chemoradiation incorporating intensity-modulated radiotherapy followed by adjuvant chemotherapy in high risk locally advanced cervical squamous cancer: a phase II study.

BACKGROUND: Although the prognosis of locally advanced cervical cancer has improved dramatically, survival for those with stage IIIB-IVA disease or lymph nodes metastasis remains poor. It is believed that the incorporation of intensity-modulated radiotherapy into the treatment of cervical cancer might yield an improved loco-regional control, whereas more cycles of more potent chemotherapy after the completion of concurrent chemotherapy was associated with a diminished distant metastasis. We therefore initiated a non-randomized prospective phaseII study to evaluate the feasibility of incorporating both these two treatment modality into the treatment of high risk locally advanced cervical cancer. OBJECTIVES: To determine whether the incorporation of intensity-modulated radiotherapy and the addition of adjuvant paclitaxel plus cisplatin regimen into the treatment policy for patients with high risk locally advanced cervical cancer might improve their oncologic outcomes. STUDY DESIGN: Patients were enrolled if they had biopsy proven stage IIIA-IVA squamous cervical cancer or stage IIB disease with metastatic regional nodes. Intensity-modulated radiotherapy was delivered with dynamic multi-leaf collimators using 6MV photon beams. Prescription for PTV ranged from 45.0 ~ 50.0 Gy at 1.8 Gy ~ 2.0 Gy/fraction in 25 fractions. Enlarged nodes were contoured separately and PTV-nodes were boosted simultaneously to a total dose of 50.0-65 Gy at 2.0- 2.6 Gy/fraction in 25 fractions. A total dose of 28 ~ 35 Gy high-dose- rate brachytherapy was prescribed to point A in 4 ~ 5 weekly fractions using an iridium- 192 source. Concurrent weekly intravenous cisplatin at 30 mg/m2 was initiated on the first day of radiotherapy for over 1-h during external-beam radiotherapy. Adjuvant chemotherapy was scheduled within 4 weeks after the completion of concurrent chemo-radiotherapy and repeated 3 weeks later. Paclitaxel 150 mg/m2 was given as a 3-h infusion on day1, followed by cisplatin 35 mg/m2 with 1-h infusion on day1-2 (70 mg/m2 in total). RESULTS: Fifty patients achieved complete response 4 weeks after the completion of the treatment protocol, whereas 2 patients had persistent disease. After a median follow-up period of 66 months, loco-regional (including 2 persistent disease), distant, and synchronous treatment failure occurred in 4,5, and 1, respectively. The 5-year disease-free survival, loco-regional recurrence-free survival, distant-metastasis recurrence-free survival was 80.5%, 90.3%, and 88.0%, respectively. Four of the patients died of the disease, and the 5-year overall survival was 92.1%. Most of the toxicities reported during concurrent chemo-radiotherapy were mild and transient. The occurrence of hematological toxicities elevated mildly during adjuvant chemotherapy, as 32% (16/50) and 4% (2/50) patients experienced grade 3-4 leukopenia and thrombocytopenia, respectively. Grade 3-4 late toxicities were reported in 3 patients. CONCLUSIONS: The incorporation of intensity-modulated radiotherapy and adjuvant paclitaxel plus cisplatin chemotherapy were highly effective and well-tolerated in the treatment of high-risk locally advanced cervical cancer. The former yields an improved loco-regional control, whereas distant metastases could be effectively eradicated with mild toxicities when adjuvant regimen was prescribed.