Gonadal Function in Male Patients With Metastatic Renal Cell Cancer Treated With Sunitinib

Background/aim: Single-agent tyrosine kinase inhibitors are still prescribed as first-line treatment to a relevant subgroup of patients with metastatic renal cell carcinoma (mRCC). These agents are known to cause disfunction of many endocrine glands (e.g., thyroid). In this two-step trial, we aimed to assess gonadal function among male patients with mRCC treated with sunitinib. Patients and methods: We enrolled a first cross-sectional cohort of pre-treated (>6 months) patients and a subsequent cohort of treatment-naïve patients who were prospectively followed-up. All patients were screened for hypogonadism and received a Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire at study entry and after 6 months of therapy. Patients who were candidates for testosterone replacement therapy (TRT) also received a FACT-G questionnaire at baseline and 3 months after supplementation. Results: Among the 30 enrolled patients, the prevalence of hypogonadism was found to be higher in those receiving sunitinib for a longer period (27.3% at baseline, 41.7% in the first 6 months, and 68.4% after 9 months of therapy). The testosterone level of patients correlated with quality of life (R=0.32). A total of six patients received TRT, with a significant improvement in their global quality of life after the first 3 months of treatment. Conclusion: An increasing prevalence of hypogonadism was seen among male patients who received long-term treatment with sunitinib. TRT was associated with relevant improvements in quality of life. These findings corroborate similar published observations and encourage the assessment of gonadal function in male patients with mRCC under treatment with sunitinib

Immunotherapy failure in adrenocortical cancer: where next?

Excerpt: Adrenocortical carcinoma (ACC) is a rare endocrine neoplasia, characterized by an overall dismal prognosis and its clinical manifestations are the consequence of either steroid excess or tumor mass progression. Surgery is the mainstay of therapy. For patients with locally advanced or metastatic ACC, not amenable to surgery, Mitotane and cytotoxic chemotherapy (with etoposide, doxorubicin and cisplatin - EDP scheme) are the systemic treatments currently in use

Expiratory flow limitation in intensive care: prevalence and risk factors

Expiratory flow limitation (EFL) is characterised by a markedly reduced expiratory flow insensitive to the expiratory driving pressure. The presence of EFL can influence the respiratory and cardiovascular function and damage the small airways; its occurrence has been demonstrated in different diseases, such as COPD, asthma, obesity, cardiac failure, ARDS, and cystic fibrosis. Our aim was to evaluate the prevalence of EFL in patients requiring mechanical ventilation for acute respiratory failure and to determine the main clinical characteristics, the risk factors and clinical outcome associated with the presence of EFL

Transparent decision support for mechanical ventilation using visualization of clinical preferences

BACKGROUND: Systems aiding in selecting the correct settings for mechanical ventilation should visualize patient information at an appropriate level of complexity, so as to reduce information overload and to make reasoning behind advice transparent. Metaphor graphics have been applied to this effect, but these have largely been used to display diagnostic and physiologic information, rather than the clinical decision at hand. This paper describes how the conflicting goals of mechanical ventilation can be visualized and applied in making decisions. Data from previous studies are analyzed to assess whether visual patterns exist which may be of use to the clinical decision maker. MATERIALS AND METHODS: The structure and screen visualizations of a commercial clinical decision support system (CDSS) are described, including the visualization of the conflicting goals of mechanical ventilation represented as a hexagon. Retrospective analysis is performed on 95 patients from 2 previous clinical studies applying the CDSS, to identify repeated patterns of hexagon symbols. RESULTS: Visual patterns were identified describing optimal ventilation, over and under ventilation and pressure support, and over oxygenation, with these patterns identified for both control and support modes of mechanical ventilation. Numerous clinical examples are presented for these patterns illustrating their potential interpretation at the bedside. CONCLUSIONS: Visual patterns can be identified which describe the trade-offs required in mechanical ventilation. These may have potential to reduce information overload and help in simple and rapid identification of sub-optimal settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12938-021-00974-5

Pathological Complete Response to Pembrolizumab plus Axitinib Combination following Serious Immune-Related Adverse Events in an Advanced Renal Cell Carcinoma Patient with a History of Rheumatoid Arthritis

Immune checkpoint inhibitors (ICIs)-based combinations have improved survival outcomes of advanced renal cell carcinoma (RCC) patients and are currently recommended as first-line treatment options. Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) of unknown etiology characterized by a chronic inflammatory process involving joints and extra-articular organs. Patients with AD are usually excluded from large randomized clinical trials investigating immunotherapeutic drugs. Therefore, little is known about clinical outcomes of patients with a history of RA treated with ICIs in real-world practice. In the present study, we report the clinical outcome of an advanced RCC patient with a history of RA treated with pembrolizumab in combination with axitinib. The patient experienced serious immune-related adverse events (irAEs) and achieved pathological complete response following only one ICI administration. Our case report shows that ICI-based combinations can be administered efficaciously in advanced RCC patients with a history of AD. However, a close monitoring of these patients is required, given the risk of irAEs and clinical exacerbations of symptoms associated with the preexisting AD. Moreover, prospective clinical data are needed to assess the hypothesis of a correlation between the onset of irAEs and AD flares and responses and survival outcomes to ICIs

Circulating Skeletal Troponin During Weaning From Mechanical Ventilation and Their Association to Diaphragmatic Function: A Pilot Study

Background: Patients with acute respiratory failure (ARF) may need mechanical ventilation (MV), which can lead to diaphragmatic dysfunction and muscle wasting, thus making difficult the weaning from the ventilator. Currently, there are no biomarkers specific for respiratory muscle and their function can only be assessed trough ultrasound or other invasive methods. Previously, the fast and slow isoform of the skeletal troponin I (fsTnI and ssTnI, respectively) have shown to be specific markers of muscle damage in healthy volunteers. We aimed therefore at describing the trend of skeletal troponin in mixed population of ICU patients undergoing weaning from mechanical ventilation and compared the value of fsTnI and ssTnI with diaphragmatic ultrasound derived parameters.Methods: In this prospective observational study we enrolled consecutive patients recovering from acute hypoxemic respiratory failure (AHRF) within 24 h from the start of weaning. Every day an arterial blood sample was collected to measure fsTnI, ssTnI, and global markers of muscle damage, such as ALT, AST, and CPK. Moreover, thickening fraction (TF) and diaphragmatic displacement (DE) were assessed by diaphragmatic ultrasound. The trend of fsTnI and ssTnI was evaluated during the first 3 days of weaning.Results: We enrolled 62 consecutive patients in the study, with a mean age of 67 ± 13 years and 43 of them (69%) were male. We did not find significant variations in the ssTnI trend (p = 0.623), but fsTnI significantly decreased over time by 30% from Day 1 to Day 2 and by 20% from Day 2 to Day 3 (p < 0.05). There was a significant interaction effect between baseline ssTnI and DE [F(2) = 4.396, p = 0.015], with high basal levels of ssTnI being associated to a higher decrease in DE. On the contrary, the high basal levels of fsTnI at day 1 were characterized by significant higher DE at each time point.Conclusions: Skeletal muscle proteins have a distinctive pattern of variation during weaning from mechanical ventilation. At day 1, a high basal value of ssTnI were associated to a higher decrease over time of diaphragmatic function while high values of fsTnI were associated to a higher displacement at each time point

A serum proteome signature to predict mortality in severe COVID-19 patients.

Here, we recorded serum proteome profiles of 33 severe COVID-19 patients admitted to respiratory and intensive care units because of respiratory failure. We received, for most patients, blood samples just after admission and at two more later time points. With the aim to predict treatment outcome, we focused on serum proteins different in abundance between the group of survivors and non-survivors. We observed that a small panel of about a dozen proteins were significantly different in abundance between these two groups. The four structurally and functionally related type-3 cystatins AHSG, FETUB, histidine-rich glycoprotein, and KNG1 were all more abundant in the survivors. The family of inter-α-trypsin inhibitors, ITIH1, ITIH2, ITIH3, and ITIH4, were all found to be differentially abundant in between survivors and non-survivors, whereby ITIH1 and ITIH2 were more abundant in the survivor group and ITIH3 and ITIH4 more abundant in the non-survivors. ITIH1/ITIH2 and ITIH3/ITIH4 also showed opposite trends in protein abundance during disease progression. We defined an optimal panel of nine proteins for mortality risk assessment. The prediction power of this mortality risk panel was evaluated against two recent COVID-19 serum proteomics studies on independent cohorts measured in other laboratories in different countries and observed to perform very well in predicting mortality also in these cohorts. This panel may not be unique for COVID-19 as some of the proteins in the panel have previously been annotated as mortality markers in aging and in other diseases caused by different pathogens, including bacteria