Clinical and Radiological Characteristics Associated with Respiratory Failure in Unilateral Lateral Medullary Infarction

BackgroundThe prognosis for unilateral lateral medullary infarction (ULMI) is generally good but may be aggravated by respiratory failure with fatal outcome. Respiratory failure has been reported in patients with severe bulbar dysfunction and large rostral medullary lesions, but its associated factors have not been systematically studied. We aimed to assess clinical and radiological characteristics associated with respiratory failure in patients with pure acute ULMI.Materials and MethodsSeventy-one patients (median age 55 years, 59 males) with MRI-confirmed acute pure ULMI were studied retrospectively. Clinical characteristics were assessed and bulbar symptoms were scored using a scale developed for this study. MRI lesions were classified into 4 groups based on their vertical extent (localized/extensive) and the involvement of the open and/or closed medulla. Clinical characteristics, bulbar scores and MRI lesion characteristics were compared between patients with and without respiratory failure.ResultsRespiratory failure occurred in 8(11%) patients. All patients with respiratory failure were male (p = 0.336), had extensive lesions involving the open medulla (p = 0.061), progression of bulbar symptoms (p=0.002) and aspiration pneumonia (p < 0.001). Peak bulbar score (OR, 7.9 [95% CI, 2.3–160.0]; p < 0.001) and older age (OR, 1.2 [95%CI, 1.0-1.6]; p=0.006) were independently associated with respiratory failure.ConclusionsExtensive damage involving the open/rostral medulla, clinically presenting with severe bulbar dysfunction, in conjunction with factors such as aspiration pneumonia and older age appears to be crucial for the development of respiratory failure in pure ULMI. Further prospective studies are needed to identify other potential risk factors, pathophysiology, and effective preventive measures for respiratory failure in these patients.     

Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture,Studied in Weight-Bearing and Non–Weight-Bearing Human Bone

We investigated mechanisms resulting in low bone mineral density (BMD) and susceptibility to fracture by comparing noncoding RNAs (ncRNAs) in biopsies of non–weight-bearing (NWB) iliac (n = 84) and weight bearing (WB) femoral (n = 18) postmenopausal bone across BMDs varying from normal (T-score > −1.0) to osteoporotic (T-score ≤ −2.5). Global bone ncRNA concentrations were determined by PCR and microchip analyses. Association with BMD or fracture, adjusted by age and body mass index, were calculated using linear and logistic regression and least absolute shrinkage and selection operator (Lasso) analysis. At 10% false discovery rate (FDR), 75 iliac bone ncRNAs and 94 femoral bone ncRNAs were associated with total hip BMD. Eight of the ncRNAs were common for the two sites, but five of them (miR-484, miR-328-3p, miR-27a-5p, miR-28-3p, and miR-409-3p) correlated positively to BMD in femoral bone, but negatively in iliac bone. Of predicted pathways recognized in bone metabolism, ECM-receptor interaction and proteoglycans in cancer emerged at both sites, whereas fatty acid metabolism and focal adhesion were only identified in iliac bone. Lasso analysis and cross-validations identified sets of nine bone ncRNAs correlating strongly with adjusted total hip BMD in both femoral and iliac bone. Twenty-eight iliac ncRNAs were associated with risk of fracture (FDR < 0.1). The small nucleolar RNAs, RNU44 and RNU48, have a function in stabilization of ribosomal RNAs (rRNAs), and their association with fracture and BMD suggest that aberrant processing of rRNAs may be involved in development of osteoporosis. Cis-eQTL (expressed quantitative trait loci) analysis of the iliac bone biopsies identified two loci associated with microRNAs (miRNAs), one previously identified in a heel-BMD genomewide association study (GWAS). In this comprehensive investigation of the skeletal genetic background in postmenopausal women, we identified functional bone ncRNAs associated to fracture and BMD, representing distinct subsets in WB and NWB skeletal sites. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

FRAIL‐HF,a Study to Evaluate the Clinical Complexity of Heart Failure in Nondependent Older Patients: Rationale,Methods and Baseline Characteristics

The clinical scenario of heart failure (HF) in older hospitalized patients is complex and influenced by acute and chronic comorbidities, coexistent geriatric syndromes, the patient's ability for self‐care after discharge, and degree of social support. The impact of all these factors on clinical outcomes or disability evolution is not sufficiently known. FRAIL‐HF is a prospective observational cohort study designed to evaluate clinical outcomes (mortality and readmission), functional evolution, quality of life, and use of social resources at 1, 3, 6, and 12 months after admission in nondependent elderly patients hospitalized for HF. Clinical features, medical treatment, self‐care ability, and health literacy were prospectively evaluated and a comprehensive geriatric assessment with special focus on frailty was systematically performed in hospital to assess interactions and relationships with postdischarge outcomes. Between May 2009 and May 2011, 450 consecutive patients with a mean age of 80 ± 6 years were enrolled. Comorbidity was high (mean Charlson index, 3.4 ± 2.9). Despite being nondependent, 118 (26%) had minor disability for basic activities of daily living, only 76 (16.2%) had no difficulty in walking 400 meters, and 340 (75.5%) were living alone or with another elderly person. In addition, 316 patients (70.2%) fulfilled frailty criteria. Even nondependent older patients hospitalized for HF show a high prevalence of clinical and nonclinical factors that may influence prognosis and are usually not considered in routine clinical practice. The results of FRAIL‐HF will provide important information about the relationship between these factors and different postdischarge clinical, functional, and quality‐of‐life outcomes.     

Microbubble dynamics and jetting near tissue-phantom biointerfaces

Precise excitation of cavitation is a promising mechanism for microsurgery procedures and targeted drug delivery enhancement. The underlying phenomenon of interest, jetting behaviour of oscillating cavitation bubbles, occurs due to near-surface interactions between the boundary, liquid, and bubble. Within this study we measured boundary effects on the cavitation bubble dynamics and morphology, with an emphasis on observation and measurement of jetting behaviour near tissue-phantom biointerfaces. An important mechanism of boundary poration has been observed using time-resolved optical microscopy and explained for different tissue-phantom surface densities and Young’s modulus. Below a critical distance to the boundary, around γ = 1.0, the resulting jets penetrated the tissue-phantom, resulting in highly localized few micrometer diameter jets.     

Adverse Events During Immunotherapy in Slovenian Patients with Metastatic Melanoma Reveal a Positive Correlation with Better Treatment Outcomes

BackgroundImmunotherapy with CTLA-4 inhibitors and PD1 checkpoint inhibitors has initiated a breakthrough in the treatment and prognosis of patients with metastatic melanoma. The survival of these patients has increased from the expected survival time of less than 12 months to at least forty months. However, immunotherapy with either anti-CTLA-4 antibodies or PD1 inhibitors alone or in combination has a broad palette of significant immune-related adverse events. The aim of the study was to assess the correlation of immune-related adverse events with treatment outcomes defined as significant differences in the overall response rate (ORR) and progression-free survival (PFS) of patients, who developed immune-related adverse events during immunotherapy.Patients and methodsA retrospective analysis of patients with metastatic melanoma treated with immunotherapy in 2020 at the Oncology Institute of Ljubljana was performed. Only patients with radiological evaluation of the immunotherapy response were included. The patients were divided into two cohorts: a cohort of patients with immune-related adverse events (irAE group) and a cohort of patients with no immune-related adverse events (NirAE group). Significantly better overall response and progression-free survival in the irAE cohort defined the primary aim of our study. To investigate the differences in progression-free survival between the irAE cohort and NirAE cohort, we used survival analysis. In particular, a Cox proportional hazards model with covariates of time to progression and adverse events was used for survival analysis. The Kruskal-Wallis H-test was applied, and a p-value of p <= 0.05 was considered the cut-off point for a statistically significant difference between the groups.ResultsAmong the 120 patients treated with immunotherapy, radiological response evaluation was performed for 99 patients: 38 patients in the irAE cohort and 61 patients in the NirAE cohort. The ORRs for the irAE and NirAE cohorts were 57% and 37%, respectively. The PFS was significantly better for the irAE cohort (301.6 days) than for the NirAE cohort (247.29 days). The results of the survival regression analysis showed a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort.ConclusionsPatients with metastatic melanoma treated with immunotherapy who developed immune-related adverse events showed better treatment outcomes with longer times to disease progression and better overall response rates than patients treated with immunotherapy who did not develop immune-related adverse events, with a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort.Key words: immune related adverse events, immunotherapy, melanoma, metastases, response, survival     

Interatrial block,frailty and prognosis in elderly patients with myocardial infarction

Background

Interatrial block (IAB) is associated with atrial fibrillation (AF) in different clinical situations, but little information exists in elderly patients with myocardial infarction (MI) and its association with frailty.