Hassanrogers2989
7 months vs. 11.1 months,
= 0.029; HR, 0.53; 95% confidence interval, 0.30-0.95). The ORR of anlotinib treatment was 48.4%. The incidence of treatment-related adverse events (TRAE) was 100% and 89.7% in the anlotinib and placebo groups, respectively. The most common TRAEs of all grades in the anlotinib group were palmar-plantar erythrodysesthesia syndrome (62.9%), proteinuria (61.3%), and hypertriglyceridemia (48.4%).
Anlotinib demonstrates its efficacy and safety in this phase IIB trial for the treatment of MTC and may become a new choice for this rare disease, especially for Chinese patients.
Anlotinib demonstrates its efficacy and safety in this phase IIB trial for the treatment of MTC and may become a new choice for this rare disease, especially for Chinese patients.
The survival rate of children with refractory/relapsed acute myeloid leukemia (R/R-AML) by salvage chemotherapy is minimal. Treatment with chimeric antigen receptor T cells (CAR T) has emerged as a novel therapy to improve malignancies treatment. C-type lectin-like molecule 1 (CLL1) is highly expressed on AML stem cells, blast cells, and monocytes, but not on normal hematopoietic stem cells, indicating the therapeutic potential of anti-CLL1 CAR T in AML treatment. This study aimed to test the safety and efficacy of CAR T-cell therapy in R/R-AML.
Four pediatric patients with R/R-AML were enrolled in the ongoing phase I/II anti-CLL1 CAR T-cell therapy trial. The CAR design was based on an apoptosis-inducing gene, FKBP-caspase 9, to establish a safer CAR (4SCAR) application. Anti-CLL1 CAR was transduced into peripheral blood mononuclear cells of the patients via lentivector 4SCAR, followed by infusion into the recipients after lymphodepletion chemotherapy. Cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and other adverse events were documented. Treatment response was evaluated by morphology and flow cytometry-based minimal residual disease assays.
Three patients with R/R-AML achieved complete remission and minimal residual disease negativity, while the other patient remained alive for 5 months. All these patients experienced low-grade and manageable adverse events.
On the basis of our single-institution experience, autologous anti-CLL1 CAR T-cell therapy has the potential to be a safe and efficient alternative treatment for children with R/R-AML, and therefore requires further investigation.
On the basis of our single-institution experience, autologous anti-CLL1 CAR T-cell therapy has the potential to be a safe and efficient alternative treatment for children with R/R-AML, and therefore requires further investigation.
No circulating biomarkers are currently available to identify patients at highest risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy.
The ECOG-ACRIN E2805 (ASSURE) trial evaluated adjuvant sunitinib, sorafenib, or placebo in resected high-risk RCC. KIM-1 levels were measured from banked plasma at trial enrollment 4-12 weeks after nephrectomy. Lognormal accelerated failure time models were used to test for association between KIM-1 and disease-free survival (DFS) as well as overall survival (OS).
Plasma from 418 patients was analyzed. Higher post-nephrectomy KIM-1 was associated with worse DFS across all study arms after adjustment for Fuhrman grade, T stage, N stage, and tumor histology [survival time ratio 0.56 for 75th vs. 25th percentile of KIM-1; 95% confidence interval (CI), 0.42-0.73;
< 0.001]. The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement (
= 0.0086). The addition of post-nephrectomy KIM-1 improved the concordance of clinical prognostic models [Stage, Size, Grade, and Necrosis (SSIGN) concordance 0.57 vs. 0.43,
= 0.05; UCLA International Staging System (UISS) concordance 0.60 vs. 0.40,
= 0.0005]. Higher post-nephrectomy KIM-1 was also associated with worse OS after multivariable adjustment (survival time ratio 0.71 for 75th vs. 25th percentile of KIM-1; 95% CI, 0.56-0.91;
< 0.001).
Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.
Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.
N-803 is an IL15 receptor superagonist complex, designed to optimize
persistence and trans-presentation, thereby activating and expanding natural killer (NK) cells and CD8
T cells. Monoclonal antibodies (mAbs) direct Fc receptor-bearing immune cells, including NK cells, to recognize and eliminate cancer targets. The ability of IL15R agonists to enhance tumor-targeting mAbs in patients has not been reported previously.
Relapsed/refractory patients with indolent non-Hodgkin lymphoma were treated with rituximab and intravenous or subcutaneous N-803 on an open-label, dose-escalation phase I study using a 3+3 design (NCT02384954). Primary endpoint was maximum tolerated dose. Immune correlates were performed using multidimensional analysis via mass cytometry and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) which simultaneously measures protein and single-cell RNA expression.
This immunotherapy combination was safe and well tolerated and resulted in durable clinical responses including in rituximab-refractory patients. Subcutaneous N-803 plus rituximab induced sustained proliferation, expansion, and activation of peripheral blood NK cells and CD8 T cells, with increased NK cell and T cells present 8 weeks following last N-803 treatment. CITE-seq revealed a therapy-altered NK cell molecular program, including enhancement of AP-1 transcription factor. Furthermore, the monocyte transcriptional program was remodeled with enhanced MHC expression and antigen-presentation genes.
N-803 combines with mAbs to enhance tumor targeting in patients, and warrants further investigation in combination with immunotherapies.
N-803 combines with mAbs to enhance tumor targeting in patients, and warrants further investigation in combination with immunotherapies.Overview of Medicines and Healthcare products Regulatory Agency. Antiepileptic drugs in pregnancy updated advice following comprehensive safety review. Drug Safety Update 2021;14(6)1.Ewing's sarcoma is an aggressive tumour, common in paediatric age, in which treatment often implies a decrease in reproductive potential. We describe a case of a woman who had a lumbar Ewing's Sarcoma in 1991, at the age of 8. She was submitted to extended tumourectomy, chemotherapy and local radiotherapy without preservation techniques. In adult life, and after two in vitro fertilization (IVF) reproductive cycles without success, she spontaneously conceived at the age of 32. After an uneventful pregnancy, she delivered a healthy child by caesarean section. This is a rare successful case of a spontaneous and uneventful pregnancy without previous preservation techniques. In the last 30 years, there has been significant development in this area, and currently, there are solutions for these patients, including in prepubertal age.Brain injury with ventricle puncture is a well-known complication of ventriculoperitoneal (VP) shunting. However, parenchymal injuries caused by a shunt tunneller are rare. Herein, we present a case of penetrating brain injury caused by a shunt tunneller during VP shunting. An 83-year-old woman with brainstem glioma underwent VP shunting to control hydrocephalus due to tumour growth. She underwent brainstem tumour biopsy with a lateral suboccipital approach. After the shunting, CT showed a linear haematoma in the left occipital lobe far from the site of the ventricular puncture. MRI revealed a small contusion in the left cerebellar hemisphere, disconnection of the left tentorial membrane and linear haematoma on a straight line. These facts suggested that the shunt tunneller had penetrated the skull through the craniotomy of the posterior fossa. This is a rare complication of VP shunting, with limited cases reported in the literature.Accessory breast tissue (ABT) is found in approximately 2%-6% of the female population and are subject to most of the physiological and pathological changes that occur in pectoral breast. Primary breast cancer occurring in ABT is a rare occurrence and a second primary breast cancer occurring in an accessory breast has never been reported. We report the case of a 60-year-old woman with a history of mastectomy for left breast cancer 5 years prior to presentation, who presented with an enlarging right axilla mass found to be a second primary breast cancer in an accessory tissue on biopsy. Many physicians are unfamiliar with the clinical presentation of accessory breast cancer due to the rarity of the condition and this ultimately results in delayed diagnosis and advanced disease at presentation. It is therefore prudent that physicians have a high index of suspicion when patients present with axillary masses.A 47-year-old man sustained multisystem injuries after being struck by a vehicle travelling at high speeds. Shortly after admission to the emergency department he suffered a ventricular tachycardia/ventricular fibrillation cardiac arrest lasting 30 min. Investigations following return of spontaneous circulation raised suspicion for an anterolateral ST-elevation myocardial infarction. Despite his major traumatic injuries the patient was transferred for percutaneous coronary intervention uncovering a complete thrombosis of the ostium of the left anterior descending artery. Immediately following coronary revascularisation, the patient developed cardiogenic shock resulting in a multidisciplinary decision to place the patient on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The management of cardiogenic shock due to acute myocardial infarction with VA-ECMO and multiple traumatic injuries were often at odds with each other, resulting in a series of challenging decisions on timing of surgery and anticoagulation. The patient was liberated from VA-ECMO after 72 hours and continues rehabilitation in hospital.A 71-year-old woman was brought in by ambulance to the emergency department with sudden-onset difficulty in breathing whilst shopping at a large UK retail shopping centre. She had no respiratory history and portable chest X-ray revealed a huge gastrothorax, secondary pneumothorax and mediastinal shift. Clinical deterioration with haemodynamic instability required urgent decompression. Successful needle decompression followed by tube thoracostomy improved patient condition with no further complications. Surgical repair was performed but was delayed by COVID-19. This case provides a rare presentation of an acute life-threatening tension gastrothorax with difficult management considerations. A review of the management options is undertaken.Pregnancy in patients with spinal cord injury presents unique challenges to their care teams. PCB chemical While spinal cord injury alters the function of several organ systems, one of the most important consequences is autonomic dysreflexia. Anaesthesia providers must be familiar with the pathophysiology and management of gravid patients with spinal cord injury to manage their deliveries successfully. A multidisciplinary team is essential; close collaboration between the obstetrical and anaesthesiology teams is crucial. The authors will present a case of a successful caesarean delivery in a woman with a T5 injury as well as a recent epidural abscess using general endotracheal anaesthesia.
