Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives.

The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response. IDH mutations have been associated with tumor development and progression in various solid tumors such as glioma, cholangiocarcinoma, chondrosarcoma, and other tumor types and have become crucial markers in molecular classification and prognostic assessment. The intratumoral and serum levels of D-2-hydroxyglutarate (D-2-HG) could serve as diagnostic biomarkers for identifying IDH mutant (IDHmut) tumors. As a result, an increasing number of clinical trials are evaluating targeted treatments for IDH1/IDH2 mutations. Recent studies have shown that the focus of these new therapeutic strategies is not only the neomorphic activity of the IDHmut enzymes but also the epigenetic shift induced by IDH mutations and the potential role of combination treatments. Here, we provide an overview of the current knowledge about IDH mutations in solid tumors, with a particular focus on available IDH-targeted treatments and emerging results from clinical trials aiming to explore IDHmut tumor-specific features and to identify the clinical benefit of IDH-targeted therapies and their combination strategies. An insight into future perspectives and the emerging roles of circulating biomarkers and radiomic features is also included.

A Systematic Review of Diagnostic and Prognostic Biomarkers for Head and Neck Cancer of Unknown Primary: An Unmet Clinical Need.

Head and neck cancer of unknown primary (HNCUP) is defined as cervical lymph node metastases without a detectable primary tumor. The management of these patients presents a challenge to clinicians since guidelines in the diagnosis and treatment of HNCUP remain controversial. An accurate diagnostic workup is fundamental for the search for the hidden primary tumor to allow the best adequate treatment strategy. The purpose of this systematic review is to present the currently available data about the diagnostic and prognostic molecular biomarkers for HNCUP. Systematic research in an electronic database was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and identified 704 articles, of which 23 studies were selected and included in the analysis. Fourteen studies investigated HNCUP diagnostic biomarkers and focused on the human papilloma virus (HPV) and the Epstein-Barr virus (EBV) due to the strong associations with oropharyngeal cancer and nasopharyngeal cancer, respectively. HPV status was shown to possess prognostic value, correlating with longer disease-free survival and overall survival. HPV and EBV are the only available HNCUP biomarkers, and they are already used in clinical practice. A better characterization of the molecular profiling and the development of tissue-of-origin classifiers are necessary to improve the diagnosis, staging, and therapeutic management of patients with HNCUP.

Mechanical thrombectomy in patients with stroke due to large vessel occlusion in the anterior circulation and low baseline NIHSS score.

We sought to verify the benefit of mechanical thrombectomy in patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation and low National Institute of Health stroke scale score at presentation. The prospective database of our stroke center was screened for patients with acute ischemic stroke due to large vessel occlusion and a baseline National Institute of Health stroke scale score ≤5 that had undergone mechanical thrombectomy. Outcome measures were the modified Rankin Scale (mRS) score at 90 days, brain bleeding events and death at 90 days. Out of 459 patients, 17 (12 females, mean age 70 ± 14 years) with occlusion of M1 or M2 segment of middle cerebral artery and baseline National Institute of Health stroke scale score ≤5 underwent mechanical thrombectomy. Eight patients (47%) were treated within 6 hours from the onset, 5 (29%) were treated beyond 6 hours, and 4 (24%) were wake-up strokes. Effective mechanical thrombectomy was achieved in 16 patients (94%) and associated with excellent functional outcomes at 3 months (mRS 0-1) in 13 (76%). The asymptomatic brain-bleeding event was observed in one patient 4 days after effective mechanical thrombectomy concerning safety issues. One patient died 1 month after mechanical thrombectomy of a cause unrelated to stroke. Our findings favor a potential benefit of mechanical thrombectomy in patients with stroke due to large vessel occlusion and low National Institute of Health stroke scale score at presentation. These patients may also benefit from a prolonged time window for treatment.

Categories of congruence between inpatient self-reported pain and nurses evaluation.

OBJECTIVE: To enhance the awareness that biased pain estimation may undermine its treatment, we sought to determine the congruence categories (CCs) between inpatient self-reported pain (PSRP) and nurse pain-evaluation (NEP) and to look for associations between CCs and inpatient and situational moderators. DESIGN: A point cross-sectional survey. SUBJECTS: The inpatient population [(n=869), > or = 6 years old and hospitalised for at least 24h] and n=115 nurses of the University of Bologna's teaching hospital, Italy. MEASURES: Using numerical rating scale, inpatients self-reported their pain while nurses indirectly rated these patients' pain using information acquired during their professional activity prior to the study and by reviewing patients' medical charts. OUTCOME MEASURES: Congruence moderator data were: gender, age, marital status, clinical area and length of hospital stay. The study was set to assess: PSRP-NEP mean of absolute difference (MAD), agreement and correlation; and to analyse the CCs dependence upon the PSRP and the congruence moderator variables. RESULTS: PSRP-NEP agreement and correlation were mild and moderate, respectively, while their MAD=2.0 (95% CI 1.8-2.2). Congruence was found in 50% of the cases. Under-estimation (21%) was directly proportional to the PSRP severity, while congruence and over-estimation (29%) were inversely proportional to it. The 'PSRP effect' on the CCs detected was further modulated by the moderators studied. CONCLUSIONS: PSRP-NEP congruence was limited while CCs were associated with PSRP, inpatient and situational moderators. Further prospective studies are needed to verify generalization and whether the studied moderators operate through patient stereotyping mechanisms. Awareness of the influence of such mechanisms on pain evaluation may ameliorate pain assessment.

Pain prevalence and predictors among inpatients in a major Italian teaching hospital. A baseline survey towards a pain free hospital.

Pain prevalence among inpatients is an important indicator of quality care; it may reach over 80% in various clinical settings. A cross-sectional survey was conducted in a teaching hospital to depict benchmark data regarding pain prevalence and predictors among the entire inpatient population. Overall 892 patients, 6 years old and hospitalized for at least 24 h in 57 hospital wards were interviewed using an internationally applied questionnaire. Patients self-reported their pain intensity at the time of the interview (T(0)) and worst pain perceived during the previous 24 h (T(-1)), using a numerical rating scale (NRS) and indicated current pain duration. Specific pain predictor data (hospital stay, gender, age and marital status) were obtained from patient medical charts. Pain prevalence at T(0) was 38% and 52% at T(-1). Pain was moderate to severe (NRS4) in approximately 25% of the patients at T(0) and in 40% at T(-1). High pain prevalence was found (at T(0) and T(-1), respectively) in Radiotherapy (63%;77%), Obstetrics (68%;54%), and Surgery (59%;45%) wards. Gender was a prominent determinant as pain was significantly associated with females. Pain prevalence was high among young adults or divorced/separated individuals and low among pediatric patients ( approximately 20%). Protracted hospitalization and prolonged pain duration were associated with major pain severity. Results yield Quality Assurance interventions to ameliorate pain undertreatment. Predictor analysis suggests that attention should be paid to pain management in young adults, socially vulnerable patients and those with protracted hospitalization and pain.