Dual specific STAT3/5 degraders effectively block acute myeloid leukemia and natural killer/T cell lymphoma.

The transcription factors STAT3, STAT5A, and STAT5B steer hematopoiesis and immunity, but their enhanced expression and activation promote acute myeloid leukemia (AML) or natural killer/T cell lymphoma (NKCL). Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, but these kinase blockers are not selective against STAT3/5 activation and frequent resistance causes relapse, emphasizing the need for targeted drugs. We evaluated the efficacy of JPX-0700 and JPX-0750 as dual STAT3/5 binding inhibitors promoting protein degradation.

Corticosteroid therapy in older adults with cancer: Expert recommendations from a task force of the International Society of Geriatric Oncology.

Corticosteroids are used frequently in oncology and many patients require short- or long-term corticosteroid therapy. General clinical guidelines and recommendations exist on the use of corticosteroids; however, evidence is lacking for recommendations on their appropriate use in older adult with cancer. Treatment of chemotherapy-induced nausea and vomiting (CINV) has dramatically improved over the last decade with 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists and neurokinin-1 (NK-1) receptor antagonists or a combination of both.

A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development.

Unlabelled: CAR T-cell product quality and stemness (Tstem) are major determinants of in vivo expansion, efficacy, and clinical response. Prolonged ex vivo culturing is known to deplete Tstem, affecting clinical outcome. YTB323, a novel autologous CD19-directed CAR T-cell therapy expressing the same validated CAR as tisagenlecleucel, is manufactured using a next-generation platform in <2 days.

Controversies in the management of patients with soft tissue sarcoma: Recommendations of the Conference on State of Science in Sarcoma 2022.

Background: Owing to the rarity and heterogeneity in biology and presentation, there are multiple areas in the diagnosis, treatment and follow-up of soft tissue sarcoma (STS), with no, low-level or conflicting evidence.

Methods: During the first Consensus Conference on the State of Science in Sarcoma (CSSS), we used a modified Delphi process to identify areas of controversy in the field of sarcoma, to name topics with limited evidence-based data in which a scientific and knowledge gap may remain and a consensus statement will help to guide patient management. We determined scientific questions which need to be addressed in the future in order to generate evidence and to inform physicians and caregivers in daily clinical practice in order to improve the outcomes of patients with sarcoma.

Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma.

Background: Patient outcomes are poor for aggressive B-cell non-Hodgkin's lymphomas not responding to or progressing within 12 months after first-line therapy. Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for diffuse large B-cell lymphoma after at least two treatment lines.

Methods: We conducted an international phase 3 trial involving patients with aggressive lymphoma that was refractory to or progressing within 12 months after first-line therapy.

Noninferiority of cetuximab every-2-weeks versus standard once-weekly administration schedule for the first-line treatment of RAS wild-type metastatic colorectal cancer.

Aim: This study assessed whether cetuximab 500 mg/m administered every 2 weeks (Q2W), when combined with chemotherapy as a first-line (1L) treatment, was noninferior to the approved dose (400 mg/m followed by 250 mg/m once weekly [Q1W]) for overall survival (OS) in adults with RAS wild-type metastatic colorectal cancer (mCRC).

Methods: This pooled analysis included patients receiving 1L treatment with cetuximab Q1W or Q2W in combination with chemotherapy from post-authorisation studies with patient-level data available to the sponsor. Baseline characteristics were adjusted with a propensity score using inverse probability of treatment weighting (IPTW).

Association of De Ritis ratio with oncological outcomes in patients with non-muscle invasive bladder cancer (NMIBC).

Purpose: The De Ritis ratio (aspartate aminotransferase/alanine aminotransferase, DRR) has been linked to oncological outcomes in several cancers. We aimed to assess the association of DRR with recurrence-free survival (RFS) and progression-free survival (PFS) in patients with non-muscle-invasive bladder cancer (NMIBC).

Methods: We conducted a retrospective analysis of 1117 patients diagnosed with NMIBC originating from an established multicenter database.

Factors predicting the need for vaginal replacement at the time of primary reconstruction of a cloacal malformation.

Background: A subset of patients with cloacal malformations requires vaginal replacement during their primary reconstruction, increasing the surgical complexity. Identifying factors which predict the need for vaginal replacement would facilitate operative planning.

Methods: We retrospectively reviewed patients who underwent primary cloacal reconstruction at our Center (2014-2018) and assessed the length of the common channel, urethra, and vagina.

Review of the outcomes of complex acetabular reconstructions using a stemmed acetabular pedestal component.

Aim: Until now, there has been no consensus as to whether stemmed acetabular components are appropriate for use in patients undergoing revision total hip arthroplasty (THA) who have major acetabular defects or pelvic discontinuity. We wished to address this deficiency in the literature.

Patients And Methods: We carried out a retrospective study of 35 patients (six men and 29 women) with a mean age of 68 years (37 to 87), with major acetabular defects who underwent revision THA between 2000 and 2012.

Single-stage revision for the infected total knee replacement: results from a single centre.

Peri-prosthetic infection is amongst the most common causes of failure following total knee replacement (TKR). In the presence of established infection, thorough joint debridement and removal of all components is necessary following which new components may be implanted. This can be performed in one or two stages; two-stage revision with placement of an interim antibiotic-loaded spacer is regarded by many to be the standard procedure for eradication of peri-prosthetic joint infection.

Independent or synergistic relationship of proteinuria and glomerular filtration rate on patient and renal survival in patients with glomerulonephritis?

Background: Glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD) identifies patients at risk for death or end-stage renal disease (ESRD). CKD staging by GFR should incorporate proteinuria to augment risk stratification. We therefore tested the predictive power of the combination of GFR with proteinuria in patients with different histologically-diagnosed types of glomerulonephritis (GN).

The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure.

Purpose: Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO(2)) in patients with chronic heart failure using (11)C-acetate positron emission tomography (PET).

Methods: We prospectively enrolled 21 patients with severe heart failure.

Her-2/neu gene amplification and over-expression in stomach and esophageal adenocarcinoma: from pathology to treatment.

Discovery of the over-expression of Her-2/neu or the amplification of its regulatory gene in stomach and esophageal cancer has resulted in targeted treatment directed at this protein. The fact itself and its consequences have been the topic of an abundance of studies and clinical trials. In the present report we review the current state of the art as regards diagnosis of the over-expression and amplification of Her-2/neu, its inhibition as a new therapeutic concept, treatment toxicity, and the development of resistance to Her-2/neu as a limiting factor in stomach and esophageal adenocarcinoma.

Markers of bone metabolism in premature myocardial infarction (≤ 40 years of age).

Introduction: Acute myocardial infarction (AMI) at young age is a rare disease with a poor prognosis. Bone metabolism parameters such as 1,25 (OH)₂ vitamin D₃, 25 (OH) vitamin D₃ and osteocalcin have been recently implicated in the development of coronary heart disease (CHD). We evaluated the role of these serum markers in a study population of very young AMI survivors (≤ 40 years).

Response of elderly patients with rheumatoid arthritis to methotrexate or TNF inhibitors compared with younger patients.

Objective: To compare the efficacy of MTX and MTX+TNF inhibitors (TNFis) in elderly patients with RA with that in patients of younger age.

Methods: Data from two large, randomized, controlled, double-blind trials in patients with early RA using adalimumab or infliximab+MTX or MTX alone were obtained and pooled. Composite disease activity indices were calculated at baseline and 1 year of treatment, and compared in groups of patients classified by quartiles of age with the highest age group comprising 61-82 years using analysis of variance or Kruskal-Wallis test.

Familial-combined hyperlipidaemia in very young myocardial infarction survivors (< or =40 years of age).

Aims: Myocardial infarction (MI) in very young individuals is a rare disease associated with an unfavourable prognosis. Familial-combined hyperlipidaemia (FCHL) increases the risk for MI in individuals below 60 years; however, its role in very young MI patients below 40 years is not as well established. We investigated the prevalence and impact of FCHL in these very young MI patients.