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Purpose: We aimed to estimate the absolute (incidence) and relative (hazard ratio; HR) risk of agranulocytosis associated with metamizole in comparison with non-steroidal antiinflammatory drugs (NSAIDs). Methods: A cohort study of new users of metamizole versus NSAIDs was performed with BIFAP (Pharmacoepidemiologic Research Database in Public Health Systems; Spain). Patients aged ≥ 2 years in 2005–2022 were followed up from the day after their first metamizole or NSAID dispensation till the end of the treatment period to identify patients hospitalized due to idiosyncratic agranulocytosis. Incidence rate (IR) and adjusted HR of agranulocytosis with metamizole versus NSAID were estimated assuming the onset date of agranulocytosis was the date of hospitalization sensitivity analysis or 7 days before (main analysis). In secondary analyses, we used (1) opioids-paracetamol as negative control and (2) any hospitalized neutropenia as outcome (assuming the onset was 7 days before). Results: The cohorts included 444,972 new users of metamizole, 3,814,367 NSAID, and 3,129,221 opioids-paracetamol on continuous treatment during a median of 37–40 days. Overall, 26 hospitalized agranulocytosis occurred, 5 in the first week (and so removed in main analysis) and 21 thereafter. IR of agranulocytosis was 14.20 (N = 5 cases) and 8.52 (N = 3), 1.95 (N = 6) and 1.62 (N = 5), and 4.29 (N = 15) and 3.72 (N = 13)/107 person-weeks of continuous treatment using the date of hospitalization or 7 days before, respectively. Two, 0 and 2 of cases identified in both analyses had neoplasia in every cohort, respectively. HR of agranulocytosis associated with metamizole was 7.20 [95% CI: 1.92–26.99] and 4.40 [0.90–21.57] versus NSAID, and 3.31 [1.17–9.34] and 2.45 [0.68–8.83] versus opioid-paracetamol, respectively. HR of neutropenia with metamizole was 2.98 [1.57–5.65] versus NSAID. Conclusions: Agranulocytosis was very rare but more common (above 4 times more) with metamizole than other analgesics. The impact of the drug-induced agranulocytosis was less precise with metamizole than the comparators due to its lower use, which precluded to find statistical differences in main analysis. The increased risk of hospitalized neutropenias with metamizole supports the link with its severity although triggers unavailable during the follow-up (ex. cytotoxic medication) can not be discarded. [ABSTRACT FROM AUTHOR]

Concern about clozapine-associated neutropenia contributes to clozapine's underutilization and racial disparities in access. People with African ancestry are more likely to have lower normative absolute neutrophil counts (ANC), associated with the Duffy null genetic polymorphism. Recent data on clozapine-associated neutropenia in the US are lacking. Patients prescribed clozapine in the Johns Hopkins Medicine electronic medical record (EMR) between 2013 and 2023 were identified. Duffy null Associated Neutrophil Count (DANC) was assigned if there were two ANC's < 2000 cells/μL, >30 days apart, before starting clozapine. Rates of neutropenia, timing of first neutropenia, and demographic differences were explored. 974 received clozapine and had ANC's available, with 63.9 % male, 51.1 % White, and 39 % Black. 287 were presumed to start clozapine during the study period, and were 62.4 % male, 46 % White, and 44.9 % Black. No patients developed severe neutropenia. 59 (6.1 %) developed mild or moderate neutropenia. 19 (6.6 %) new starts had presumed DANC, and none developed neutropenia. 11 of 16 presumed new starts who developed neutropenia did so within eight months. No demographic differences were found between groups for presumed new starts. For non-new starts, where DANC assignment was not possible, Black patients were more likely than White patients to develop neutropenia (OR 3.48, 95 % CI [1.65, 7.73]). To our knowledge, this is the first observational study of clozapine-associated neutropenia in the US in the past decade, and it includes a substantial proportion of Black patients. ANC monitoring requirements may be too strict, contributing to clozapine underutilization. [ABSTRACT FROM AUTHOR]

Background: Levamisole is less expensive and has a better toxicity profile compared to other steroid sparing agents used in nephrotic syndrome. It has a plasma half-life of 2.0 to 5.6 hours, but is conventionally administered on alternate days. We aimed to assess whether daily levamisole is safe and more effective than standard alternate-day therapy in maintaining remission in children with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). Methods: An open-label randomized controlled trial was conducted in children with FR/SDNS. Group A received daily while Group B received alternate-day levamisole (2–3 mg/kg/dose) for 12 months. Prednisolone was tapered off by 3 months. Patients were monitored for relapses, further steroid requirement, and adverse effects. Results: A total of 190 children with FR/SDNS (94 in Group A and 96 in Group B) were analyzed. Sustained remission for 12 months was observed in 36% of Group A and 27% of Group B patients (p = 0.18). Numbers completing 12 months in the study were 67% in Group A and 56% in Group B (p = 0.13). Time to first relapse, persistent FR/SDNS, and withdrawal due to poor compliance were statistically similar in both groups, while relapse rate and cumulative steroid dosage were significantly lower in Group A compared to Group B (p = 0.03 and p = 0.02, respectively). The incidence of adverse effects was comparable in both groups, with reversible leucopenia and hepatic transaminitis being the commonest. Conclusions: Daily levamisole therapy was not superior to alternate-day therapy in maintaining sustained remission over 12 months. Nevertheless, relapse rate and cumulative steroid dosage were significantly lower without increased adverse effects. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Insurance coverage for oral valganciclovir (VGCV) began in Japan in April 2023 on the basis of results, including our clinical trials for symptomatic congenital cytomegalovirus (CMV) disease. The VGCV treatment is available throughout Japan, so clinicians must consider the likelihood of hearing improvement and the possibility of neutropenia before dosing. We performed a substudy of an investigator-initiated, single-arm, prospective, multicenter, clinical trial in which 24 infants with symptomatic congenital CMV disease were orally administered 16 mg/kg VGCV twice daily for 6 months as an intervention. We examined the infants' baseline characteristics associated with improved hearing impairment or a severely reduced neutrophil count. Of the 24 patients, 4 had normal hearing on assessment of their ear with the best hearing. Hearing impairment improved in 14 patients and did not respond to VGCV treatment in 6 patients at the 6-month hearing assessment. CMV DNA levels in plasma at baseline were higher in patients in whom hearing did not respond to treatment. A neutrophil count <500/mm3 occurred in 5 (21%) patients for the first 6 weeks and in 8 (33%) patients for the first 6 months. A neutrophil count at screening and the lowest neutrophil count over the 6 months showed the highest correlation (r = 0.477, p = 0.019). Infants with a low plasma viral load at screening tend to have an improvement in hearing impairment. Clinicians should be aware of neutropenia during VGCV treatment particularly in patients with a low neutrophil count during screening. [ABSTRACT FROM AUTHOR]

Neutropenia refers to a decrease in the absolute neutrophil count according to age and race norms and poses a common concern in pediatric practice. Neutrophils serve as host defenders and act crucially in acute inflammation procedures. In this narrative review, we systematically present causes of neutropenia in childhood, mainly adopting the pathophysiological classification of Frater, thereby studying (1) neutropenia with reduced bone marrow reserve, (2) secondary neutropenia with reduced bone marrow reserve, and (3) neutropenia with normal bone marrow reserve. Different conditions in each category are thoroughly discussed and practically approached from the clinician’s point of view. Secondary mild to moderate neutropenia is usually benign due to childhood viral infections and is expected to resolve in 2–4 weeks. Bacterial and fungal agents are also associated with transient neutropenia, although fever with severe neutropenia constitutes a medical emergency. Drug-induced and immune neutropenias should be suspected following a careful history and a detailed clinical examination. Cytotoxic chemotherapies treating malignancies are responsible for severe neutropenia and neutropenic shock. Rare genetic neutropenias usually manifest with major infections early in life. Our review of taxonomies clinical findings and associates them to specific neutropenia disorders. We consequently propose a practical diagnostic algorithm for managing neutropenic children.

Abstract Objective This retrospective study aimed to investigate the factors influencing the occurrence of neutropenia in patients with endometrial cancer (EC) following adjuvant chemoradiotherapy (CRT). Methods Retrospective analysis of EC patients who underwent adjuvant CRT from January 2012 to June 2023 in the Department of Gynecology and Oncology of the First Affiliated Hospital of Shandong First Medical University. Neutropenia was defined as an Absolute Neutrophil Count (ANC) of peripheral blood neutrophils below 2 × 109/L. Factors affecting neutropenia in EC patients treated with CRT using Generalized Estimating Equation (GEE), and Logistic regression was used to further analyze the effect of adding radiotherapy to different chemotherapy cycles on neutropenia, so that patients receive optimal adjuvant CRT while the risk of neutropenia is appropriately controlled. Results A total of 144 patients met the inclusion criteria. They underwent 330 cycles of adjuvant chemotherapy, of whom 96 (66.7%) developed neutropenia, which occurred 140 times. The results of one-way GEE analysis showed that before CRT, White Blood Cell (WBC) (OR = 0.827; 95%CI, 0.701–0.976), ANC (OR = 0.749; 95%CI, 0.586–0.957), Absolute Monocyte Count (AMC) (OR = 0.047; 95%CI, 0.008–0.283), Blood Urea Nitrogen (BUN) (OR = 0.857; 95%CI, 0.741–0.991), platinum and docetaxel (platinum/docetaxel) dosing regimen (OR = 2.284; 95%CI, 1.130–4.618) were associated with neutropenia with adjuvant CRT for EC (p

Aim: We present a case of Ecthyma gangrenosum (EG) affecting left thigh in a child with acute lymphoblastic leukaemia (ALL) with an aim to raise awareness about this condition. Case presentation: A 7-year-old female child who presented with lethargy, pallor and lumps to inner lip was diagnosed with B-cell precursor ALL. She was started on treatment as per UKALL 2011 guidelines Regime B. On day 28, she developed neutropenic sepsis along with a new lesion in her left thigh. She was started on intravenous Meropenum, Gentamicin and Caspofungin. The clinical diagnosis of EG was made based on lesion progression, positive blood and wound swab & tissue cultures for Pseudomonas aeruginosa and patient's immunocompromised status. The wound healed with secondary intention following debridement. We present a series of photographs to demonstrate her remarkable improvement. Discussion: EG occurs in 1–30% of cases of Pseudomonas sepsis; other bacteria and fungi can be associated with this condition. It is identified more in oncology patients as seen in our patient. A multidisciplinary team approach should be provided in 3 stages with empirical antibiotics, followed by targeted antibiotics or antifungals & surgical debridement. Our patient was treated in similar fashion and made a good recovery. Conclusion: It is a rare skin condition associated with a high mortality. We suggest all clinicians to be vigilant about this condition to be able to provide accurate diagnosis and prompt treatment to improve the overall prognosis.

Introduction: Systemic lupus erythematosus (SLE), the commonest type of lupus, is an autoimmune multisystemic disorder that can affect any organ system of the body, especially blood vessels and connective tissues, causing widespread inflammation. Pediatric onset of SLE is a rare condition with more hematological involvement. Aim: This study was undertaken to observe various hematological abnormalities and their association with various autoantibodies present in pediatric SLE in Eastern India. Methodology: It was a single-centered, cross-sectional, observational, hospital-based study conducted in the Department of Pediatric Medicine in collaboration with the Department of Rheumatology in IPGME and R and SSKM Hospital, Kolkata. The duration of the study was 1.5 years, and a total of 30 children up to 12 years of age of either gender were enrolled. Study participants were evaluated for various parameters like demographic, hematological (anemia, neutropenia, leucopenia, lymphopenia, and thrombocytopenia), biochemical (CRP, Lactate dehydrogenase (LDH), and bilirubin), autoantibodies (anti-dsDNA, anti-Ro 52, and anti-Ribonucleoprotein [RNP]), and SLE related pathologies (Cutaneous, nephritis, serositis). Results: In the present study, most of the participants had arthritis, muscle pain (86.66%), and hematological involvement (80%). Among cytopenias, anemia was the commonest. dsDNA autoantibody was positive in most of the patients (83%), and about one-third suffered from autoimmune hemolytic anemia (AIHA). No association was observed between autoantibodies and various hematological manifestations. Conclusion: It can be concluded from the present study that anemia is the most common cytopenia in pediatric SLE, but there is no association between autoantibodies and these cytopenias. However, study on larger population may give better results.

Abstract Background Traditional dosing of chemotherapy drugs based on body surface area may overdose small dogs, leading to an increased frequency of adverse events (AEs). Hypothesis/Objectives Evaluate the frequency of hematologic and gastrointestinal AEs in dogs with newly diagnosed lymphoma treated with vincristine weighing ≤15 kg in comparison to dogs weighing >15 kg. We hypothesized that dogs weighing ≤15 kg would experience a higher frequency of AEs. Animals One hundred and thirty‐eight dogs with newly diagnosed lymphoma were treated with vincristine. Methods A multicenter retrospective study reviewing hematologic data and medical record information. Complete blood counts were performed no more than 24 hours before vincristine administration and then between 4 and 8 days post‐administration. Data were evaluated using logistic regression or ordinal logistic regression. Results Thirty‐eight dogs weighing ≤15 kg and 100 dogs weighing >15 kg were included. The median vincristine dose for both groups was 0.6 mg/m2. Seventeen (12.3%) instances of neutropenia occurred with no significant difference in overall frequency or grade between groups. Thirty initially asymptomatic substage A dogs (29.4%) experienced gastrointestinal AEs. Because of the widespread use of gastrointestinal supportive care medications, statistical comparison between groups could not be performed. Seven instances of hospitalization occurred (5.0%) and the risk of hospitalization did not differ significantly between groups (P = .37). Conclusions and Clinical Importance Vincristine dosed at ≤0.6 mg/m2 does not increase the risk of hematologic AEs in dogs weighing ≤15 kg.

Purpose: Anatomical structures and organ preservation concepts of the head and neck are important for patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC). Neoadjuvant chemotherapy has been applied to improve organ preservation; however, pathological complete remission is still unsatisfactory. The purpose of this study was to explore the pathological complete response (pCR) rate and safety of immune checkpoint blockade combined with neoadjuvant chemotherapy (NAC) in patients with LA HNSCC. Methods: Fifty-one patients participated in this retrospective study, and of these, 25 received NAC only (cisplatin+5-fluorouracil+nab-paclitaxel), and 26 received NAC (cisplatin+5-fluorouracil) plus pembrolizumab. Pathological complete remission, the objective response rate (ORR), delayed surgery and toxicity were compared between the two groups. Results: A significant difference was observed in the pCR rate and ORR between the NAC+ICB group and the NAC group. Delaying surgery and Grade 3 or 4 AEs occurred more frequently in the NAC group. In the NAC-only group, during a median follow-up period of 31.80 months, the recurrence-free survival (RFS) rate was 80.0%, the disease-free survival (DFS) rate was 80.0% and the overall survival (OS) rate was 88.0%. In the NAC+ICB group, during the median follow-up period of 22.99 months, the RFS rate was 96.2%, the DFS rate was 96.2% and the OS rate was 100%. Conclusion: The combination of pembrolizumab with NAC could improve the pathological response without increasing the risk of toxicity, which provides pathological evidence for the treatment of LA HNSCC patients with NAC+ICB. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion The recommended dosage of pegylated recombinant human granulocyte‐colony stimulating factor (PEG‐rhG‐CSF) for Western chemotherapy patients is 6 mg per cycle. However, for Eastern Asians, the optimal dose remains unknown.This open‐label, randomized, non‐inferiority trial (NCT05283616) enrolled Chinese female breast cancer patients receiving adjuvant chemotherapy. Participants were randomized to receive either 3 or 6 mg of PEG‐rhG‐CSF per cycle, stratified by body weight (BW; ≤60 kg vs. >60 kg). The primary endpoint was timely absolute neutrophil count (ANC) recovery before the second cycle of chemotherapy.A total of 122 patients were randomized and 116 were included for efficacy analyses. The timely ANC recovery rate in the 3 mg arm was 89.8%, compared to 93.0% in the 6 mg arm (one‐sided 95% confidence interval [CI] lower limit for difference: −11.7%), meeting the prespecified non‐inferiority margin of 15%. The rate was 93.3% with PEG‐rhG‐CSF 3 mg and 96.6% with 6 mg in patients with BW ≤ 60 kg, and 86.2% and 89.3%, respectively, in those with BW > 60 kg. Although the incidence of severe neutropenia was similar across arms, the occurrence of excessively high ANC and white blood cell counts was higher in the 6 mg arm. No grade ≥3 adverse events related to PEG‐rhG‐CSF occurred.Three milligrams of PEG‐rhG‐CSF per cycle provided non‐inferior neutrophil protection and attenuated neutrophil overshoot compared to 6 mg doses. This low‐dose regimen could be a new supportive care option for Chinese breast cancer patients receiving anthracycline‐based adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Glycogen storage disease type 1b (GSD-1b) is characterized by neutropenia and neutrophil dysfunction generated by the accumulation of 1,5- anhydroglucitol-6-phosphate in neutrophils. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, facilitate the removal of this toxic metabolite and ameliorate neutropenia-related symptoms, including severe infections and inflammatory bowel disease (IBD). Our case series presents the treatment of three pediatric GSD-1b patients with empagliflozin over a follow-up of three years; the most extended reported follow-up period to date. Cases description: A retrospective analysis of empagliflozin treatment of three pediatric GSD-1b patients (two male and one female; ages at treatment initiation: 4.5, 2.5 and 6 years) was performed. Clinical and laboratory data from a symmetrical period of up to three years before and after the therapy introduction was reported. Data on the clinical course of the treatment, IBD activity, the need for antibiotic treatment and hospitalizations, neutrophil count and function, and markers of inflammation were assessed. Prior the introduction of empagliflozin, patients had recurrent oral mucosa lesions and infections, abdominal pain, and anemia. During empagliflozin treatment, the resolution of aphthous stomatitis, termination of abdominal pain, reduced frequency and severity of infections, anemia resolution, increased appetite, and improved wound healing was observed in all patients, as well as an increased body mass index in two of them. In a patient with IBD, long-term deep remission was confirmed. An increased and stabilized neutrophil count and an improved neutrophil function enabled the discontinuation of G-CSF treatment in all patients. A trend of decreasing inflammation markers was detected. Conclusions: During the three-year follow-up period, empagliflozin treatment significantly improved clinical symptoms and increased the neutrophil count and function, suggesting that targeted metabolic treatment could improve the immune function in GSD-1b patients. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study aimed to investigate the factors influencing the occurrence of neutropenia in patients with endometrial cancer (EC) following adjuvant chemoradiotherapy (CRT). Methods: Retrospective analysis of EC patients who underwent adjuvant CRT from January 2012 to June 2023 in the Department of Gynecology and Oncology of the First Affiliated Hospital of Shandong First Medical University. Neutropenia was defined as an Absolute Neutrophil Count (ANC) of peripheral blood neutrophils below 2 × 109/L. Factors affecting neutropenia in EC patients treated with CRT using Generalized Estimating Equation (GEE), and Logistic regression was used to further analyze the effect of adding radiotherapy to different chemotherapy cycles on neutropenia, so that patients receive optimal adjuvant CRT while the risk of neutropenia is appropriately controlled. Results: A total of 144 patients met the inclusion criteria. They underwent 330 cycles of adjuvant chemotherapy, of whom 96 (66.7%) developed neutropenia, which occurred 140 times. The results of one-way GEE analysis showed that before CRT, White Blood Cell (WBC) (OR = 0.827; 95%CI, 0.701–0.976), ANC (OR = 0.749; 95%CI, 0.586–0.957), Absolute Monocyte Count (AMC) (OR = 0.047; 95%CI, 0.008–0.283), Blood Urea Nitrogen (BUN) (OR = 0.857; 95%CI, 0.741–0.991), platinum and docetaxel (platinum/docetaxel) dosing regimen (OR = 2.284; 95%CI, 1.130–4.618) were associated with neutropenia with adjuvant CRT for EC (p < 0.05), results of multifactorial GEE analysis showed that before adjuvant CRT ANC (OR = 0.552; 95%CI, 0.973–2.231), AMC (OR = 0.047; 95%CI, 0.004–0.052), platinum/docetaxel (OR = 2.437; 95%CI, 1.087–5.464) were an independent influence on neutropenia in adjuvant CRT for EC (p < 0.05). Multifactorial Logistic regression shows addition of radiotherapy to the first cycle of chemotherapy (OR = 4.413; 95%CI, 1.238–18.891) was an independent influence of neutropenia (p < 0.05). Conclusions: Patients with low pre-CRT ANC and AMC, platinum/docetaxel dosing regimens need to be closely monitored during each cycle of CRT. Also, the concurrent addition of radiotherapy should be avoided during the first cycle of chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: The efficacy and safety of different doses of PEG recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the prevention of leukopenia/neutropenia during concurrent chemoradiotherapy for cervical cancer were investigated. Methods: The patients who received concurrent radiotherapy and chemotherapy for cervical cancer from June 2020 to January 2023 were selected to evaluate the difference in efficacy, adverse reactions, and treatment cost of PEG-rhG-CSF in the prevention of leukopenia/neutropenia between the test group and the control group. Results: The minimum value of leukopenia/neutropenia in the test group was significantly higher than that in the control group (P < 0.05). The incidence of grade ≥ 3 leukopenia/neutropenia was significantly lower than that of the control group (P < 0.05). The number of interrupted days of radiotherapy was less than that of the control group (P < 0.05). PEG-rhG-CSF of different prophylactic doses (100 μg/kg dose or 50 μg/kg dose) had similar prophylactic effects in the test group, OR=1.192 (0.761, 1.868), P=0.443. Conclusion: Prophylactic application of PEG-rhG-CSF could reduce the incidence of leukopenia/neutropenia in cervical cancer during concurrent chemoradiotherapy. There was no significant difference in efficacy and safety with prophylactic use of drug at doses of 100 μg/kg and 50 μg/kg. [ABSTRACT FROM AUTHOR]

A study conducted by the European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias (EuNet-INNOCHRON) and other organizations examined the impact of COVID-19 on patients with chronic neutropenia (CNP). The study collected data from 57 CNP patients infected with SARS-CoV-2 between March 2020 and May 2022. The findings showed that CNP patients experienced similar symptoms to the general population, with fever, cough, and musculoskeletal pains being the most frequently reported. The study also found that isolated CNP did not increase the risk of severe COVID-19 infection unless other comorbidities were present. Patients on long-term granulocyte colony-stimulating factor (G-CSF) treatment were more likely to develop musculoskeletal symptoms and shortness of breath, but these symptoms were not severe enough to require hospitalization. The study concluded that CNP patients should be treated according to local protocols and that initiation of G-CSF treatment is generally not necessary. Further research is needed to assess the relative susceptibility of CNP patients to SARS-CoV-2. [Extracted from the article]

Background: Immunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated. Methods: Retrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups. Results: A total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre‐specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes. Conclusion: The 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission. [ABSTRACT FROM AUTHOR]

Introduction: According to the PRISMA criteria, a systematic review has been conducted to investigate the clinical relevance between patients with severe congenital neutropenia (SCN) and cyclic congenital neutropenia (CyN) induced by ELANE mutations. Methods: We have searched PubMed, EMBASE, Web of Science, Scopus, Cochrane, CNKI, Wanfang Medicine, and VIP for ELANE mutation related literature published from 1997 to 2022. Using Microsoft Excel collect and organize data, SPSS 25, GraphPad Prism 8.0.1, and Omap analyze and plot statistical. Compare the gender, age, geography, mutation sites, infection characteristics, treatment, and other factors of SCN and CyN patients induced by ELANE mutations, with a focus on exploring the relationship between genotype and clinical characteristics, genotype and prognosis. Results: This study has included a total of 467 patients with SCN and 90 patients with CyN. The onset age of SCN and CyN are both less than 1 year old, and the onset and diagnosis age of SCN are both younger than CyN. The mutation of ELANE gene is mainly missense mutation, and hot spot mutations include S126L, P139L, G214R, c.597+1G>A. The high-frequencymutations with severe outcomes are A57V, L121H, L121P, c.597+1G>A, c.597+1G>T, S126L, C151Y, C151S, G214R, C223X. Respiratory tract, skin and mucosa are the most common infection sites, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli are the most common. Discussion: Patients with refractory G-CSF are more likely to develop severe outcomes. The commonly used pre-treatment schemes for transplantation are Bu-Cy-ATG and Flu-Bu-ATG. The prognosis of transplantation is mostly good, but the risk of GVHD is high. [ABSTRACT FROM AUTHOR]

Les infections urinaires représentent les infections bactériennes les plus fréquemment documentées en pédiatrie. Les choix thérapeutiques proposés dans ce guide sont issus des recommandations publiées par le Groupe de pathologie infectieuse pédiatrique (GPIP), la Société française de pédiatrie (SFP) et la Société de pathologie infectieuse de langue française (SPILF). En dehors de situations particulières (nouveau-né, neutropénie, sepsis), une bandelette urinaire positive pour les leucocytes ou les nitrites doit précéder la réalisation d'un examen cytobactériologique des urines et toute antibiothérapie. Après avoir augmenté régulièrement entre 2000 et 2012, la proportion de souches de Escherichia coli résistantes par production de ß-lactamases à spectre étendu (E-BLSE) est stable ces dix dernières années, entre 7 et 10 % en pédiatrie. Cependant, il n'est pas exceptionnel qu'aucun antibiotique administrable par voie orale ne soit actif, conduisant soit à prolonger le traitement parentéral, soit à utiliser une association non-orthodoxe comme céfixime + acide-clavulanique. Dans l'objectif d'épargner les antibiotiques de la classe des pénèmes et de favoriser la prise en charge ambulatoire, ce guide privilégie un traitement initial des infections urinaires fébriles en cas de suspicion ou d'infection à E-BLSE, par l'amikacine. Celle-ci reste active sur la majorité des souches d'enterobacterales productrices de ß-lactamases à spectre étendu. Elle est donnée en monothérapie pour les patients pris en charge aux urgences pédiatriques ou hospitalisés. Urinary tract infections are the most frequently proven bacterial infections in pediatrics. The treatment options proposed in this guide are based on recommendations published by the Groupe de Pathologie Infectieuse de Pédiatrique (GPIP-SFP). Except in rare situations (newborns, neutropenia, sepsis), a positive urine dipstick for leukocytes and/or nitrites should precede a urine culture examination and any antibiotic therapy. After rising steadily between 2000 and 2012, the proportion of Escherichia coli strains resistant to extended-spectrum ß-lactamases (E-ESBL) has remained stable over the last ten years (between 7 % and 10 % in pediatrics). However, in many cases no oral antibiotic is active on E-ESBL leading either to prolonged parenteral treatment, or to use of a non-orthodox combination such as cefixime + clavulanate. With the aim of avoiding penem antibiotics and encouraging outpatient management, this guide favors initial treatment of febrile urinary tract infections (suspected or actual E-ESBL infection), with amikacin. Amikacin remains active against the majority of E-ESBL strains. It could be prescribed as monotherapy for patients in pediatric emergency departments or otherwise hospitalized patients. [ABSTRACT FROM AUTHOR]

Background Neutropenic sepsis frequently requires admission to an intensive care unit (ICU). Differences between subgroups of patients with neutropenic sepsis are not well characterized. Aims To investigate clinical outcomes among patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis. Methods Retrospective cohort study of all patients admitted to ICU in Australia or New Zealand between January 2000 and December 2022 with a primary admission diagnosis of sepsis and total white cell count <1.0 × 109 cells/L. Results We identified 8617 ICU admissions with neutropenic sepsis (hematological malignancy n = 4660; metastatic solid cancer n = 1034; no cancer n = 2800). Patients with hematological malignancy were younger (median, 61.5 years) with low rates of chronic comorbidities (4.7%) and were usually admitted to ICU from the ward (67.4%). Mechanical ventilation rates were 20.2% and in-hospital mortality was 30.6%. Patients with metastatic solid cancers were older (median, 66.3 years), with higher rates of chronic comorbidities (9.9%), and were usually admitted to the ICU from the emergency department (50.8%). Mechanical ventilation rates were 16.9% and in-hospital mortality was 42.4%. Patients with no documented cancer had highest rates of mechanical ventilation (41.7%) and mortality (46.3%). Neutropenia was independently associated with mortality among patients with solid cancers or no cancer but did not confer increased risk among patients with hematological malignancy (odds ratio, 0.98; 95% confidence interval,.90–1.06; P =.60). Conclusions Patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis constitute 3 distinct clinical groups. Management approaches should be tailored accordingly. [ABSTRACT FROM AUTHOR]

Background: Agranulocytosis is a rare antithyroid drug treatment (ATD) side effect seen in children suffering from Graves' disease (GD). Neutropenia is a recognized adverse event associated with ATD but has also been reported as pre-treatment neutropenia in GD. Methods: We performed a retrospective cohort study to analyze the longitudinal clinical and biochemical data of 161 pediatric patients with GD who received either methimazole (MMI) or carbimazole (CBZ) as ATD. The inclusion criteria were elevated free thyroxine (fT4 >25 pmol/L), suppressed thyrotropin (TSH <0.05 mlU/mL), and elevated thyrotropin receptor antibodies (TSHRAbs >2.5 IU/L). Absolute neutrophil count (ANC) was used to define neutropenia (ANC <1800/µL) and agranulocytosis (ANC <500/µL). Results: Nine of the 161 patients had neutropenia at diagnosis (ANC: 1348/µL ± 250) without further deterioration under ATD. In this subgroup, we found higher levels of free triiodothyronine (fT3: 31.45 pmol/L ± 3.99) at diagnosis in comparison with those who developed neutropenia (26.29 pmol/L ± 12.96; p = 0.07) and those without neutropenia before and during therapy (23.12 pmol/L ± 13.7; p = 0.003). Thirty-eight patients (23.6%) became neutropenic (ANC: 1479/µL ± 262) while receiving ATD. Neutropenia occurred after a mean of 551.8 (range: 10–1376) days, mostly without further deterioration. Two of these 38 patients developed agranulocytosis and underwent emergency thyroidectomy. The patients with neutropenia were significantly younger (p = 0.031). Neutropenia occurred significantly more often in patients receiving CBZ (50%; n = 20/40) than in those receiving MMI (16.5%; n = 18/110; p = 0.001). The minimum ANC was significantly lower in the CBZ (1971/µL ± 1008) than in the MMI group (2546 ± 959); p = 0.004. Conclusions: Neutropenia occurred significantly more often under CBZ than MMI. As this is potentially due to higher immunogenicity, we suggest that children with GD should be treated with MMI. Frequent measurements of ANC may be needed to detect severe agranulocytosis, although low pre-treatment ANC may not necessarily be a contraindication to ATD treatment. Young age may be potentially associated with an increased risk of reduced ANC. Further investigation is necessary to fully understand risk factors for neutropenia in children with GD. [ABSTRACT FROM AUTHOR]

Extraosseous Ewing's sarcoma is an extremely rare tumor. In the literature, intestinal Ewing's sarcoma was reported in 20 cases, and omental Ewing's sarcoma was reported in only two cases. In this case report, we report a 23-year-old female who presented with the complaint of diffuse abdominal pain. Abdominal ultrasound and whole-body computed tomography revealed a mass starting from the adnexal area and extending between the intestinal loops. Serum levels of tumor markers were high. The serum levels of carbohydrate antigen-125 (CA-125) and carcinoembryonic antigen-19.9 (CA-19.9) were high (427.5 U/mL and 67.9 U/mL, respectively). Laparotomic exploration was performed with the preliminary diagnosis of an adnexal mass, and a mass originating from the small intestine meso and completely covered by the omentum was excised. Histological evaluation reported intestinal and omental origin of Ewing's sarcoma. This case highlights the importance of rare extraosseous Ewing's sarcoma, which should be included in the differential diagnosis of a young female with intra-abdominal mass. [ABSTRACT FROM AUTHOR]

Simple Summary: Ramucirumab (RAM) + docetaxel (DTX) therapy is recommended as a second-line treatment for non-small cell lung cancer (NSCLC) and pretreatment with immune checkpoint inhibitors (ICIs) has been reported to improve the therapeutic efficacy of this therapy. Meanwhile, caution should be exercised for the development of febrile neutropenia during this treatment and preventing the onset of neutropenia while continuing the treatment is greatly important. This study found that previous treatment with ICIs reduced the incidence of grade ≥ 3 neutropenia after RAM + DTX therapy in patients with NSCLC, regardless of the influences of pretreatment with cytotoxic anticancer agents. A history of ICI treatment may have a similar influence on carcinomas other than NSCLC. In the present study, the influence of previous immune checkpoint inhibitor (ICI) therapy with ramucirumab (RAM) + docetaxel (DTX) therapy on the occurrence of severe neutropenia in patients with non-small cell lung cancer (NSCLC) was evaluated, taking into account the influences of cytotoxic chemotherapy used in pretreatment. The study participants included patients who received a combination therapy of RAM and DTX as cancer chemotherapy for NSCLC. The influences of previous ICI treatment and pretreatment with cytotoxic anticancer agents on the development of grade ≥ 3 neutropenia were analysed. A total of 89 patients, including 50 with and 39 without a history of ICI treatment, were analysed. Kaplan-Meier curves showed a significant difference in the influence of previous ICI treatment on the development of grade ≥ 3 neutropenia (p = 0.006). Moreover, Cox regression analysis identified a history of ICI treatment and prophylactic administration of G-CSF as factors associated with the development of grade ≥ 3 neutropenia (p = 0.018 and p < 0.001, respectively). This study found that previous treatment with ICIs reduced the incidence of grade ≥ 3 neutropenia after RAM + DTX therapy in patients with NSCLC, regardless of the influences of pretreatment with cytotoxic anticancer agents. [ABSTRACT FROM AUTHOR]

Purpose: Febrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data. Methods: A retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group. Results: 7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI=0: $23,095; NCI >0-2: $26,084; NCI ≥2: $26,851). Conclusions: FN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios. [ABSTRACT FROM AUTHOR]

Background: Infective endocarditis (IE) is a serious complication of bloodstream infections (BSIs) that occurs at variable rates depending on the pathogen and clinical setting. There is a paucity of data describing the risk of IE in patients with hematologic malignancy who develop bacteremia while neutropenic. Methods: Adult patients on the hematology ward from January 2018 to December 2020 with hematologic malignancy and bacteremia were evaluated retrospectively for endocarditis by applying the 2023 Duke‐ISCVID criteria. Charts of possible cases were evaluated 90 days after the initial BSI for new infectious complications that could indicate missed IE. Descriptive statistics compared patients admitted for hematopoietic stem cell transplantation (HSCT) to those admitted for alternative reasons (non‐HSCT). Results: Among the 1005 positive blood cultures initially identified, there were 66 episodes in 65 patients with hematologic malignancy and at least grade 3 neutropenia for a mean duration of 11.4 days during their admission. Transthoracic echocardiography (TTE) was performed in 34.8% of BSIs, and transesophageal echocardiography (TEE) in 6.1%. There were no new infectious complications in possible cases 90 days after their initial BSI. No cases of endocarditis were identified. Conclusions: Endocarditis is rare amongst patients with hematologic malignancy, bacteremia, and neutropenia, and no cases were identified in this cohort. The use of routine TTE in this setting seems unwarranted, and the addition of TEE is unlikely to improve patient‐centered outcomes. [ABSTRACT FROM AUTHOR]

Neutropenia refers to a decrease in the absolute neutrophil count according to age and race norms and poses a common concern in pediatric practice. Neutrophils serve as host defenders and act crucially in acute inflammation procedures. In this narrative review, we systematically present causes of neutropenia in childhood, mainly adopting the pathophysiological classification of Frater, thereby studying (1) neutropenia with reduced bone marrow reserve, (2) secondary neutropenia with reduced bone marrow reserve, and (3) neutropenia with normal bone marrow reserve. Different conditions in each category are thoroughly discussed and practically approached from the clinician's point of view. Secondary mild to moderate neutropenia is usually benign due to childhood viral infections and is expected to resolve in 2–4 weeks. Bacterial and fungal agents are also associated with transient neutropenia, although fever with severe neutropenia constitutes a medical emergency. Drug-induced and immune neutropenias should be suspected following a careful history and a detailed clinical examination. Cytotoxic chemotherapies treating malignancies are responsible for severe neutropenia and neutropenic shock. Rare genetic neutropenias usually manifest with major infections early in life. Our review of taxonomies clinical findings and associates them to specific neutropenia disorders. We consequently propose a practical diagnostic algorithm for managing neutropenic children. [ABSTRACT FROM AUTHOR]

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia. In Japan, its use requires management by a blood monitoring system called the Clozaril Patient Monitoring Service (CPMS) for the early detection of serious side effects such as agranulocytosis, which is extremely rare. Monitoring services vary among the clozapine suppliers in different countries. Additionally, Japanese patients can be started on clozapine treatment exclusively through an 18-week inpatient admission at a psychiatric hospital capable of coordinating with a hematologist. One reported reason for the lack of widespread clozapine use in Japan is the difficulty in establishing collaboration with hematologists when agranulocytosis/leukopenia occurs. Hence, we conducted a nationwide web-based survey of CPMS-registered psychiatric facilities in Japan to determine the status of collaboration with hematology departments. Valid responses were received from the psychiatrists responsible for prescribing clozapine at 203 of the 547 facilities (response rate: 37.1 %). The largest number of psychiatric facilities (61 %) collaborated with hematologists at another facility with a psychiatry department, while psychiatrists in 32 % of the facilities worked with hematologists at their own facilities. Most patients with clozapine-induced agranulocytosis/leukopenia could be treated with clozapine discontinuation and follow-up in psychiatric inpatient units with the assistance of a hematologist. The actual workload of hematologists was limited, and the patients might experience the burden of repeated blood sampling. This study suggests that disseminating information regarding the status of collaborations with hematologists may promote the widespread use of clozapine in Japan. This study suggests that most patients with clozapine-induced agranulocytosis/leukopenia could be treated with clozapine discontinuation and follow-up in psychiatric inpatient units with the assistance of a hematologist. [ABSTRACT FROM AUTHOR]

After the introduction of clozapine eight Finnish patients died after developing agranulocytosis. Clozapine was withdrawn from the market and only reintroduced with strict mandatory white blood cell monitoring as long as treatment lasts and thresholds at which clozapine must be discontinued definitively. The fear of agranulocytosis and the need for intensive blood monitoring is the single most important barrier for prescribers and patients alike and leads to underprescription of the only effective and approved medication for treatment-resistant schizophrenia. We summarize evidence that the risk of agranulocytosis is smaller than perceived at the time of reintroduction, is concentrated in the first 18 weeks of treatment, is not greater than with other antipsychotics thereafter and that frequent blood monitoring has not demonstrably decreased the rate of agranulocytosis. Therefore we propose 1) mandatory monitoring of the absolute neutrophil count (ANC) exclusively during the first 18 weeks of clozapine treatment, 2) that thereafter the prescriber and the well-informed patient decide together about further monitoring frequency, 3) that clozapine treatment must be stopped if the ANC falls below 1.0 × 109/L. Continuation of clozapine or a rechallenge are possible if prescriber and patient determine that the benefits outweigh the risks. 4) National registries which control the haematologic monitoring are unnecessary and do not help to reduce clozapine-induced agranulocytosis. They should at least be restricted to the first 18 weeks of clozapine use. [ABSTRACT FROM AUTHOR]

To identify the risks and benefits of clozapine‑lithium co-prescription. Articles published in English or French were identified with a MEDLINE, Web of Sciences and PsycINFO search, from inception through January 2023, using the term 'clozapine' in combination with 'lithium'. Data were synthesized narratively. Of the 67 articles included in the review, more than half (n = 38, 56.7 %) were focused on clozapine-related blood dyscrasia. A body of evidence drawn from case reports and retrospective chart studies highlights the potential benefits of lithium prescription for clozapine-related neutropenia, since this strategy may avoid clozapine discontinuation or allow its rechallenge. The most documented adverse drug reactions (ADRs) associated with clozapine‑lithium co-prescription are neurotoxic events, which may be prevented or detected early by clinical, electroencephalographic and therapeutic drug monitoring. Causality assessment cannot be established for other reported ADRs occurring during clozapine‑lithium co-prescription. The benefits of the combined prescription on psychotic and/or mood symptoms are poorly documented. The risks and benefits of clozapine‑lithium co-prescription require further exploration as the combination might significantly contribute to reducing underprescription or premature discontinuation of clozapine. [ABSTRACT FROM AUTHOR]

Background: Research is limited on the role of antibodies against human neutrophil antigen (HNA) in hematopoietic progenitor cell (HPC) transplantation outcomes. Study Design and Methods: A retrospective review was conducted on medical records of patients at the NIH Clinical Center enrolled in six research protocols. This case–control study included 21 patients tested for HNA antibodies from January 2010 to March 2022 who underwent HPC transplantation. In addition, 42 patients following the same research protocols were randomly selected as a control group. Results: The cumulative incidence of time to neutrophil engraftment was significantly impacted by the patients' anti‐HNA status (p =.042), with the patients with anti‐HNA experiencing delayed engraftment. Secondary graft failure occurred in 4 out of 42 patients (9.52%; 95% confidence interval [CI]: 3.7–22.1) of the control group, while 5 out of 9 patients (55.5%; 95% CI: 26.7–81.1) with anti‐HNA experienced secondary graft failure (p =.005). Furthermore, patients with anti‐HNA had a lower proportion (p =.008 for full and p =.002 for partial chimerism) and cumulative incidence (p =.016 for full and p =.010 for partial chimerism) of achieving donor chimerism compared to the control group. Discussion: The study reveals a potential link between anti‐HNA and HPC transplantation outcomes not previously reported. Patients with anti‐HNA had a lower proportion and cumulative incidence of achieving donor chimerism. Additionally, anti‐HNA status affected the time for neutrophil engraftment, with a slower rate of neutrophil engraftment and increased risk of secondary failure in patients with anti‐HNA. [ABSTRACT FROM AUTHOR]

BACKGROUND: The management of and monitoring for hematologic adverse events associated with oral cyclin-dependent kinase (CDK) 4/6 inhibitors present unique challenges for providers and patients. Oncology pharmacists need to be familiar with drug manufacturers' recommendations and advance their clinical practice by assisting providers in the care of women with advanced breast cancer. This article highlights one institution's experience of using a pharmacist-driven approach to monitor the hematologic adverse events of CDK4/6 inhibitors and supplements the current literature with real-world patient outcomes. OBJECTIVE: To evaluate the outcomes of a pharmacist-driven approach in the monitoring for hematologic adverse events after receiving CDK4/6 inhibitors in women with advanced breast cancer. METHODS: Women aged ≥18 years with advanced breast cancer who initiated treatment with a CDK4/6 inhibitor at St Luke's Cancer Institute between September 26, 2022, and March 26, 2023, were identified. The prospective analysis identified and excluded patients if they did not initiate treatment with a CDK4/6 inhibitor within the study period. A total of 2 cohorts were identified, including patients who received CDK4/6 inhibitors within a medically integrated pharmacy who were managed by oncology clinical pharmacists (pharmacist-driven approach) and patients who received drugs through external fulfillment and were managed per usual care (non-pharmacist-driven). Data on the demographics and adverse events, such as diarrhea, that resulted from treatment with a CDK4/6 inhibitor were collected from the patients who met the inclusion criteria. RESULTS: A total of 32 patients were analyzed in the prospective chart review, with palbociclib and abemaciclib accounting for the majority of new prescriptions. Overall, >50% of patients managed by oncology clinical pharmacists in the medically integrated pharmacy achieved the manufacturer-recommended laboratory monitoring for neutropenia. Less than 20% of the patients receiving follow-up care outside the medically integrated pharmacy achieved the recommended monitoring, which represents a stark contrast compared with pharmacist-driven management. A total of 4 events of grade 3 neutropenia were observed, and early interventions by oncology clinical pharmacists occurred during treatment cycle 1. CONCLUSION: The results of this observational study show that patients receiving CDK4/6 inhibitors who were monitored by oncology clinical pharmacists obtained the recommended laboratory monitoring, which led to more timely interventions of neutropenia during treatment cycle 1. [ABSTRACT FROM AUTHOR]

Purpose: Myelosuppressive chemotherapy-induced neutropenia (CIN) remains a major limitation of cancer treatment efficacy, necessitating very expensive supportive care. Lithium carbonate, an inexpensive drug, can increase the number of neutrophils, possibly providing an efficacious and cost-effective alternative for treating CIN. The aim of this study was to determine whether lithium therapy can attenuate chemotherapy-induced neutropenia and leukopenia in breast cancer patients. Methods: A total of 50 breast cancer patients were enrolled in this prospective, interventional, randomized, controlled, and single-blind study. The patients were divided into two groups: a control group (group 1, N = 25 patients) and a lithium-treated (treatment) group (group 2, N = 25 patients). Group 1 patients were further subclassified into a non-neutropenic control group (N = 16) and a neutropenic control (N = 9) based on the subsequent development of severe neutropenia, or not. The control group received 4 cycles of doxorubicin or epirubicin plus cyclophosphamide followed by 2 cycles of paclitaxel. The treatment group received the same regimen as the control group as well as oral lithium carbonate throughout the chemotherapy cycles. Results: The results showed that the absolute neutrophil count (ANC) was increased in the lithium-treated group, while it was markedly reduced in both the non-neutropenic and neutropenic control groups (by 55.56% and 65.42% post-4 chemotherapy cycles, and by 19.57% and 39.90% post-6 cycles, respectively). The same pattern of alterations was observed for the total white blood cell count in both the control and treatment groups. In addition, the incidence and period prevalence were greatly reduced in the lithium-treated group compared to non-neutropenic and neutropenic control groups. Conclusion: Lithium therapy ameliorated chemotherapy-induced leukopenia and neutropenia in breast cancer patients. This may provide a new strategy for cost-effective treatment of CIN, particularly in Egyptian cancer patients. [ABSTRACT FROM AUTHOR]

Background: Methotrexate (MTX) at a dose of ≤25 mg/week is one of the most prescribed disease-modifying anti-rheumatic drugs (DMARDs) in a variety of rheumatic diseases. It can potentially cause life-threatening neutropenic sepsis, and acute renal and hepatotoxicity when taken inadvertently at high doses. We aim to analyse the clinical profile and risk factors of patients who presented with acute MTX toxicity. Methods: All patients presenting to the Rheumatology department with a history of inadvertent consumption of higher doses of MTX (>25 mg/week), from July 2021 to May 2023 were included. Additional data was extracted from hospital electronic medical health records. The clinical profile, risk factors, and outcome of patients with MTX toxicity were analysed. Results: The median age of the patients in our cohort was 52 IQR (40–62.5) years, with 80% females. The median cumulative dose of MTX was 120 mg (IQR 95–150). The reason for overdose in our cohort was medication error in comprehending once-weekly dosing. The most common major adverse event was neutropenia (80%). All our patients had stomatitis, with half of them having oral bleeding. Gastrointestinal adverse events like vomiting and diarrhoea were seen in 60% and 13% of the patients, respectively. Our cohort had two patients who succumbed to the complications due to neutropenic sepsis. The dose of MTX did not correlate with the severity of the disease or duration of hospital stay; however, the latter was significantly influenced by lower absolute neutrophil count (ANC). Conclusion: Acute MTX toxicity is one of the severe rheumatological emergencies and the toxicity profile includes haematological, gastrointestinal, hepatic, and renal adverse events. Severe neutropenia leading to sepsis can be fatal if not intervened early. [ABSTRACT FROM AUTHOR]

Aim: The use of tumor necrosis factor-alpha (TNF-α) inhibitors is associated with potential side effects such as infusion reactions, anaphylaxis, development of infection, and cutaneous and paradoxical side effects. We evaluated the side effects observed with the use of these agents in patients with rheumatic diseases followed by TNF-α inhibitors in our clinic. Material and Methods: Patients admitted to our clinic in the last 5 years with a diagnosis of inflammatory rheumatic disease and treated with TNF-α inhibitors were included in the study. Demographic data, diagnoses, treatment, and side effects were recorded. Statistical analysis was performed using SPSS version 21.0. Results: Forty-two patients with rheumatic disease receiving TNF-α inhibitors were analyzed. Infliximab had cutaneous side effects in 26 patients, including one infusion reaction and two cases of anaphylaxis. These side effects included allergic rash, psoriasis, bullous pemphigoid, dermatitis herpetiformis, erythema AB Igne, dermatitis, and small vessel vasculitis. Golimumab caused neutropenia in two patients. The other adverse events were cervical intraepithelial lesions and Kaposi's sarcoma in one patient with psoriatic arthritis. Infections were the most common adverse events and were reported in four patients. Conclusion: TNF-α inhibitors are widely used in the treatment of inflammatory rheumatic diseases. These agents have side effects, and it is important to be aware of and cautious about potential side effects. [ABSTRACT FROM AUTHOR]

Giant inclusions in leukocytes is a common feature that can be observed in some infections but can be also related to rare genetic disorders such as Chédiak-Higashi syndrome (CHS). A differential diagnosis between these groups of diseases has to be performed using specific genetic tests. Clinical and pathological history is relevant for a diagnostic orientation due to the difficulty and specificity of the diagnostic confirmation. We present the case of a 3-years-old male patient with recurrent respiratory infections. It is important to highlight the presence of a lock of white hair on the front of the head and some hypopigmentation of the skin. In the blood smear, the presence of big cytoplasm granules in all the leukocytes, especially in neutrophils. CHS is an uncommon genetic disorder caused by the mutation in the LYST gene situated in chromosome 1q42.3 which codified for LYST protein. Molecular genetic testing also can be done to detect the biallelic variants in the LYST gene. It is essential to perform peripheral blood smears in the presence of changes in quantitative and/or qualitative values in the complete blood count as a first step in the diagnosis algorithm. [ABSTRACT FROM AUTHOR]

Shwachman Diamond Syndrome (SDS) is a multi-system disease characterized by exocrine pancreatic insufficiency with malabsorption, infantile neutropenia and aplastic anemia. Life-threatening complications include progression to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), critical deep-tissue infections and asphyxiating thoracic dystrophy. In most patients, SDS results from biallelic pathogenic variants in the SBDS gene, different combinations of which contribute to heterogenous clinical presentations. Null variants are not well tolerated, supporting the theory that the loss of SBDS expression is likely lethal in both mice and humans. A novel complex genotype (SBDS:c.[242C>G;258+2T>C];[460-1G>A]/WFS1:c.[2327A>T];[1371G>T]) was detected in a family with recurrent neonatal deaths. A female neonate died three hours after birth with hemolytic anemia, and a male neonate with severe anemia, thrombocytopenia and neutropenia succumbed on day 40 after Staphylococcus epidermidis infection. A subsequent review of the literature focused on fatal complications, complex SBDS genotypes and/or unusual clinical presentations and disclosed rare cases, of which some had unexpected combinations of genetic and clinical findings. The impact of pathogenic variants and associated phenotypes is discussed in the context of data sharing towards expanding scientific expert networks, consolidating knowledge and advancing an understanding of novel underlying genotypes and complex phenotypes, facilitating informed clinical decisions and disease management. [ABSTRACT FROM AUTHOR]