BACKGROUND

Lithium has been known as a second-line treatment for hyperthyroidism. However, it has a narrow therapeutic range especially in patients with impaired renal function. Toxicity can cause neurological, gastrointestinal, cardiovascular, and renal symptoms, including rare cases of renal failure needing renal replacement therapy. This case report highlights a rare instance of acute lithium toxicity in a patient with multinodular goiter and chronic kidney disease, following methimazole-induced agranulocytosis.

A 55-year-old Filipino woman with chronic kidney disease and multinodular toxic goiter who developed methimazole-induced agranulocytosis presented with altered mental status after pre-treatment with lithium. Laboratory tests confirmed elevated lithium levels, consistent with acute lithium toxicity. She developed acute kidney injury, necessitating urgent hemodialysis with hemoperfusion. After two sessions, her neurological status and renal function improved. The patient resumed pre-treatment with carbimazole and subsequently underwent successful RAI then maintained on levothyroxine for long-term thyroid management

Lithium toxicity is rare but can cause life-threatening complications, particularly in patients with pre-existing kidney disease. Hemodialysis remains the treatment of choice for severe toxicity, significantly improving patient outcomes. Lithium toxicity can occur even within therapeutic levels, emphasizing the need for careful monitoring. This case highlights the importance of clinical vigilance when using lithium.

Introduction: Autoimmune thyroid disease is frequently associated with other immune-mediated disorders; however, clinically significant pancytopenia is rare. In patients with Graves’ disease receiving antithyroid therapy, leukopenia raises concern for drug-induced agranulocytosis, a rare but potentially life-threatening complication characterized by severe neutropenia requiring immediate drug withdrawal. The coexistence of hemolytic anemia and thrombocytopenia may instead suggest Evans syndrome, defined by autoimmune hemolytic anemia with immune thrombocytopenia, with or without neutropenia. Importantly, uncontrolled thyrotoxicosis itself may cause immunemediated cytopenias, creating a diagnostic challenge. Case: We report a 55-year-old female with thyroid receptor antibody-positive Graves’ disease who presented with jaundice and pancytopenia while receiving carbimazole therapy. Laboratory evaluation demonstrated anemia with reticulocytosis and a positive direct antiglobulin test, thrombocytopenia and leukopenia. Complement testing revealed reduced C3 with normal C4, consistent with immune-mediated hemolysis. Peripheral blood film showed no blast cells or marrow infiltration, and autoimmune screening, including antinuclear antibodies and anti–double stranded DNA, was negative. The coexistence of Coombs-positive hemolysis and thrombocytopenia initially raised suspicion for Evans syndrome, while leukopenia during carbimazole therapy prompted concern for drug-induced agranulocytosis. However, neutropenia was not severe, and the absence of marrow infiltration or systemic autoimmune disease made alternative causes of pancytopenia less likely. Importantly, blood counts progressively improved following the optimization of thyroid control despite continuation of carbimazole at a reduced dose, without the use of immunosuppressive therapy. This clinical course supported the interpretation of thyrotoxicosis-associated immune cytopenia rather than primary Evans syndrome or carbimazole-induced agranulocytosis. Conclusion This case highlights thyrotoxicosis-associated immune cytopenia as an important mimic of Evans syndrome and carbimazole-related hematological toxicity. Recognizing this entity is essential to avoid unnecessary discontinuation of antithyroid therapy or inappropriate immunosuppressive treatment.
Evans Syndrome ; Carbimazole ; Pancytopenia ; Agranulocytosis ; Graves Disease

Objective To investigate the clinical features of neutropenia after splenectomy in patients with hepatolenticular degeneration， also known as Wilson's disease （WD）， and related influencing factors. Methods The patients with WD who were hospitalized and underwent splenectomy from January 2018 to March 2023 were enrolled as subjects. The patients with an absolute neutrophil count of <1.7×109/L at 1 year after splenectomy were enrolled as observation group， and those with an absolute neutrophil count of ≥1.7×109/L were enrolled as control group. The two groups were compared in terms of the change in routine blood test results at 1 year after splenectomy， as well as the indicators such as general information，preoperative myelogram data， preoperative Child-Pugh score， preoperative spleen size， surgical procedures， and postoperative laboratory markers， and the influencing factors for the reduction in neutrophil count were analyzed. Results A total of 61 patients were included. At 1 year after splenectomy， both groups had significant increases in white blood cell count， neutrophil count， red blood cell count， and platelet count and a significant reduction in the percentage of neutrophils （P<0.05）. After surgery， 39.34%（24/61） of the patients still had a neutrophil count lower than the normal level. Before surgery， compared with the control group，the observation group had significantly higher Child-Pugh score， total bilirubin（TBIL），aspartate aminotransferase， and prothrombin time and a significantly lower level of albumin（ALB）（P<0.05）， and there was also a significant difference in the proportion of patients with ascites between the two groups（P<0.05）. The multivariate analysis showed that preoperative Child-Pugh score， TBIL， and ALB were independent influencing factors for neutropenia. Conclusion Splenectomy cannot completely correct neutrophil level in WD patients， which may be associated with the degree of liver damage.
Splenectomy ; Neutropenia

OBJECTIVE: To explore the clinical features and genetic basis for a child with 3-methylglutaconic aciduria type VII. METHODS: A child who was diagnosed at the Gansu Provincial Maternity and Child Health Care Hospital on August 9, 2019 was selected as the study subject. Clinical data of the child, including urine gas chromatography and mass spectrometry, were collected. The child and her parents were subjected to whole exome sequencing. RESULTS: The child, a female neonate, had presented mainly with intermittent skin cyanosis, convulsions, hypomagnesemia, apnea, neutropenia after birth. Her urine 3-methylpentenedioic acid has increased to 17.53 μmol/L. DNA sequencing revealed that she has harbored compound heterozygous variants of the CLPB gene, namely c.1016delT (p.L339Rfs*5) and c.1087A>G (p.R363G), which were respectively inherited from her mother and father. Both variants were unreported previously. Based on the standards from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively predicted to be pathogenic and likely pathogenic. CONCLUSION The child was diagnosed with 3-methylglutenedioic aciduria type VII. Discovery of the c.1016delT and c.1087A>G variants has enriched the mutational spectrum of the CLPB gene.
Female ; Humans ; Infant, Newborn ; Pregnancy ; Base Sequence ; Metabolism, Inborn Errors/diagnosis* ; Mutation ; Neutropenia/genetics* ; Sequence Analysis, DNA

OBJECTIVE: To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children. METHODS: The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared. RESULTS: A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G⁺), the most common multi-drug resistant G⁺ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G^- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011). CONCLUSIONS The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.
Humans ; Child ; Shock, Septic ; Retrospective Studies ; Sepsis ; Risk Factors ; Bacteria ; Leukemia, Myeloid, Acute/complications* ; Acute Disease ; Escherichia coli ; Anti-Infective Agents ; Agranulocytosis

OBJECTIVE: To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML). METHODS: The clinical data, treatment outcomes, complications, and blood product consumption of 6 children with refractory/relapsed AML treated with VAC regimen in the Children's Hospital of Soochow University from August 2021 to December 2021 were retrospectively analyzed. RESULTS: Among the 6 children, there were 1 male and 5 females. 5 cases were refractory AML, and 1 case was relapsed AML, which recurred again 16 months after allogeneic hematopoietic stem cell transplantation. 4 children were accompanied by chromosomes or genes that predicted poor prognosis, such as RUNX1, FLT3-ITD, KMT2A exon 2-exon 8 dup, MLL-AF6, 7q-, KMT2A exon 2-exon 10 dup, etc. After received VAC regimen, 4 cases achieved CR+CRi, 1 case achieved PR (only MRD did not relieve, MRD was 0.59%), and 1 case was NR (but the proportion of bone marrow blasts decreased). All 6 patients had grade Ⅳ neutropenia, and 4 patients had grade Ⅳ thrombocytopenia. During the period of neutropenia, none of the 6 children developed symptoms of infection such as fever, cough, and diarrhea. No treatment-related death occurred. CONCLUSION Venetoclax combined with azacitidine followed by cladribine provides a new treatment option for patients with relapsed/refractory AML who have poor efficacy in early induction remission theragy, showing good efficacy and safety.
Child ; Female ; Humans ; Male ; Azacitidine/therapeutic use* ; Cladribine/therapeutic use* ; Retrospective Studies ; Leukemia, Myeloid, Acute/genetics* ; Neutropenia ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Humans ; Mutation ; Congenital Bone Marrow Failure Syndromes/genetics* ; Neutropenia/genetics* ; Leukocyte Elastase/genetics*

Chemotherapy-induced neutropenia (CIN) is a common hematological adverse events and dose-limiting toxicities of chemotherapy. CIN may lead to dose reduction and delay of chemotherapeutic agents, febrile neutropenia and severe infection, which results in increased treatment cost, reduced efficacy of chemotherapy, and even life-threatening morbidities. Assessment of risk of CIN, early detection of FN and infection, and proper prevention and treatment play a crucial role in reducing the occurrence of CIN-related morbidities, improving patient treatment safety and anticancer efficacy. Based on evidence and expert opinion, the expert committee of Chinese Anti-Cancer Association issued "the consensus on diagnosis and treatment of chemotherapy-induced neutropenia in China (2023 edition)", which is an update version of the 2019 edition, aiming to provide reference for the diagnosis and treatment of CIN for Chinese oncologists.
Humans ; Granulocyte Colony-Stimulating Factor ; Consensus ; Neutropenia/prevention & control* ; Neoplasms/drug therapy* ; Antineoplastic Agents/adverse effects* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).
Humans ; Antineoplastic Agents/adverse effects* ; Maximum Tolerated Dose ; Neoplasms/drug therapy* ; Neutropenia/chemically induced* ; Prospective Studies

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10⁹, 0.50×10⁹, 0.48×10⁹, 0.48×10⁹/L to 1.48×10⁹, 3.04×10⁹, 1.10×10⁹, 0.73×10⁹/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans ; Child ; Child, Preschool ; Adolescent ; Prospective Studies ; Glycogen Storage Disease Type I/drug therapy* ; Neutropenia ; Abdominal Pain ; Diarrhea/drug therapy* ; Hypoglycemia