Case report: Dual-targeted BCMA and CS1 CAR-T-cell immunotherapy in recurrent and refractory extramedullary multiple myeloma.

Background: The development of CAR-T-cell immunotherapy has notably elevated the efficacy of treating multiple myeloma. Currently, a variety of targets, including BCMA, CS1, CD38, FcRH5, and GPRC5D, are being investigated. Despite these significant advancements, challenges such as antigen escape, limited persistence of CAR-T cells, and the intricate nature of the tumor microenvironment persist, leading to relapses following treatment. Case presentation: We report the case of a patient with recurrent and refractory multiple myeloma (RRMM) who developed a substantial extramedullary plasmacytoma in the muscles of the lower limb following multiple rounds of radiotherapy and chemotherapy. The patient underwent CAR-T-cell immunotherapy targeting BCMA and CS1; however, the tumor progressed despite treatment. Surgical resection of the extramedullary plasmacytoma was subsequently performed. Upon comparison of the tumor tissue with the adjacent tissue, increased expression of MYBL2 was noted in the tumor tissue, potentially contributing to the lack of improvement in extramedullary relapse after dual-targeted CAR-T cell therapy. Conclusions: In patients with recurrent and refractory multiple myeloma who underwent multiple cycles of chemotherapy and radiotherapy, dual-targeted CAR-T cell therapy aimed at BCMA and CS1 failed to effectively manage extramedullary relapse. Elevated expression of MYBL2 in multiple myeloma correlates with a poorer prognosis.

Association of acetaminophen use with perinatal outcomes among pregnant women: a retrospective cohort study with propensity score matching.

BACKGROUND: Although acetaminophen is widely used in women during pregnancy, its safety has not been clearly stated. The study aimed to investigate the association between acetaminophen use and adverse pregnancy outcomes in pregnant women in China. METHODS: We conducted a retrospective cohort study by collecting data on pregnant women who delivered in the Beijing Obstetrics and Gynecology Hospital from January 2018 to September 2023. An acetaminophen use group and a control group were formed based on prenatal exposure to acetaminophen. The pregnancy outcomes that we focused on were stillbirth, miscarriage, preterm birth, APGAR score, birth weight, and congenital disabilities. Pregnant women exposed to acetaminophen were matched to unexposed in a 1:1 ratio with propensity score matching, using the greedy matching macro. SPSS software was used for statistical analysis. Multivariable logistics regression was used to assess the association between acetaminophen use during pregnancy and adverse pregnancy outcomes. RESULTS: A total of 41,440 pregnant women were included, of whom 501 were exposed to acetaminophen during pregnancy, and 40,939 were not exposed. After the propensity score matching, the acetaminophen use and control groups consisted of 501 pregnant women each. The primary analysis showed that acetaminophen exposure during pregnancy was associated with an increased risk of stillbirth (adjusted OR (aOR) = 2.29, 95% CI, 1.19-4.43), APGAR score < 7 at 1 min (aOR = 3.28, 95% CI, 1.73-6.21), APGAR score < 7 at 5 min (aOR = 3.54, 95% CI, 1.74-7.20), APGAR score < 7 at 10 min (aOR = 3.18, 95% CI, 1.58-6.41), and high birth weight (HBW) (aOR = 1.75, 95% CI, 1.05-2.92). Drug exposure during the first and second trimesters increased the odds of stillbirth, miscarriage, APGAR < 7, and the occurrence of at least one adverse pregnancy outcome. In addition, the frequency of drug use more than two times was associated with a higher risk of preterm birth and APGAR score < 7. CONCLUSIONS: Exposure to acetaminophen during pregnancy was significantly associated with the occurrence of adverse pregnancy outcomes, particularly exposure in the first and second trimesters and frequency of use more than twice. It is suggested that acetaminophen should be prescribed with caution in pregnant women.

In vivo antitumor efficacy of 17-AAG loaded PMMA in a human multiple myeloma xenograft mouse model.

Multiple myeloma (MM) is a monoclonal malignancy characterized by abnormal proliferation of plasma cells. The disease clinically manifests as anemia, hypercalcemia, renal insufficiencies, and osteolytic damage. Osteolytic damage goes with severe bone pain, spinal instability, and pathological fracture, symptoms that are collectively referred to as multiple myeloma bone disease (MMBD). Polymethylmethacrylate (PMMA) bone cement is widely used for bone repair after MMBD surgery, owing to its excellent biomechanical properties and fast curing. To date, however, efficacy of drug-loading PMMA in inhibition of tumor growth and angiogenesis remains unknown. Here, we report that 17-AAG-loaded PMMA bone cement inhibits MM growth in vivo and suppresses tumor diffusion to peripheral tissues. In addition, 17-AAG-loaded PMMA promotes MM apoptosis by downregulating Bax and active Caspase-3.

Paraplegia secondary to disseminated mucormycosis: case report and literature review.

BACKGROUND: We report a case of spine infection with mucormycosis that manifested signs of paraplegia in a patient suffering from disseminated mucormycosis. Timely and effective surgery was performed. A review of the literature is included. CASE PRESENTATION: A patient with diabetic ketoacidosis complained of back pain and fatigue for one month, and his right lower extremity activity had been limited for 10 days. T4-T6 vertebral and paravertebral soft tissue-involved infections were identified by MRI, which were derived from right lung pneumonia. He underwent abscess debridement, spinal canal decompression, pedicle screw fixation and amphotericin B liposome injection. Histopathological examination revealed broad aseptate hyphae suggestive of invasive mucormycosis. There was improvement in neurological function after surgical and medical treatment. Three months after the surgery, the patient died of uncontrollable massive bleeding of the urinary system. Mucormycosis is characterized by rapid development and a high mortality rate. This case shows the significance of a multidisciplinary team in the diagnosis and treatment of patients with mucormycosis. In addition, orthopedic surgeons should design appropriate surgery plans for spine-involved mucormycosis patients. CONCLUSION: This case present a patient with paraplegia caused by the spread of pulmonary mucormycosis to the vertebral and paravertebral soft tissue of levels T4-T6. After medical treatment, surgical debridement and internal fixation, the patient recovered well but later patient died of possible disease dissemination to the renal or urinary tract which resulted in massive haemorrhage.

Polymorphisms of methalenetetrahydrofolate reductase in recurrent pregnancy loss: an overview of systematic reviews and meta-analyses.

PURPOSE: The aim is to summarize and evaluate current systematic reviews and meta-analyses on MTHFR polymorphisms in recurrent pregnancy loss (RPL). METHODS: We searched Pubmed and Embase databases and selected in form of PICOS (participants, interventions, comparisons, outcomes, and study design). Our methodology was registered on PROSPERO (CRD42017042762). Systematic reviews and meta-analyses containing primary studies were extracted for meta-analyses, along with their OR and 95%CI. We assessed the quality of the included studies using AMSTAR and OQAQ criteria. RESULTS: Eleven systematic reviews and meta-analyses were identified. C677T was significantly related to RPL overall in Allele (OR, 95%CI 1.43, 1.29-1.60), Recessive (OR, 95%CI 1.66, 1.42-1.95), and Homozygous (OR, 95%CI 2.08, 1.66-2.61). There was no correlation observed between A1298C and RPL, except for in Heterozygous (OR, 95%CI 1.62, 1.17-2.25). CONCLUSIONS: We identified a difference in the association between MTHFR C677T polymorphism and RPL, especially in Asian population. No significant correlation was found between A1298C and RPL.

[Molecular genetic analysis of mitochondrial DNA C1494T mutation in non-syndromic hearing loss of Chinese population].

OBJECTIVE: To conduct a molecular epidemiological survey on the mitochondrial DNA C1494T mutation in non-syndromic hearing loss patients in Chinese population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to screen the mitochondrial DNA 12S rRNA C1494T mutation in 20 patients with aminoglycoside antibiotic induced hearing loss, 136 sporadic non-syndromic hearing loss patients and 50 probands of pedigrees with non-syndromic hearing loss. RESULTS: The C1494T mutation did not appear in all cases except for the positive control. CONCLUSION: Incidence of mitochondrial DNA C1494T mutation is much lower than that of mitochondrial DNA A1555G mutation in non-syndromic hearing loss of Chinese population. Mitochondrial DNA C1494T mutation may be a rare variation in non-syndromic hearing loss and is not the main cause of aminoglycoside antibiotic induced-deafness.