Real-Time Phase-Contrast MRI to Monitor Cervical Blood and Cerebrospinal Fluid Flow Beat-by-Beat Variability

Beat-by-beat variability (BBV) rhythms are observed in both cardiovascular (CV) and intracranial (IC) compartments, yet interactions between the two are not fully understood. Real-Time Phase-Contrast (RT-PC) MRI sequence was acquired for 30 healthy volunteers at 1st cervical level on a 3T scanner. The arterial (AF), venous (VF), and cerebrospinal fluid (CSF) flow (CSFF) were computed as velocity integrals over the internal carotid artery, internal jugular vein, and CSF. AF, VF, and CSFF signals were segmented in inspiration and expiration beats, to assess the respiration influence. Systolic and diastolic BBV, and heart period series underwent autoregressive power spectral density analysis, to evaluate the low-frequency (LF, Mayer waves) and high frequency (HF, respiratory waves) components. The diastolic VF had the largest BBV. LF power was high in the diastolic AF series, poor in all CSFF series. The pulse wave analyses revealed higher mean amplitude during inspiration. Findings suggests a possible role of LF modulation of IC resistances and propagation of HF waves from VF to AF and CCSF. PC-RT-MRI could provide new insight into the interaction between CV and IC regulation and pave the way for a detailed analysis of the cerebrovascular effects of varied respiration patterns due to exercise and rehabilitation

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

The role of lung colonization in connective tissue disease-associated interstitial lung disease

Connective tissue diseases (CTDs) may frequently manifest with interstitial lung disease (ILD), which may severely impair quality and expectation of life. CTD-ILD generally has a chronic clinical course, with possible acute exacerbations. Although several lines of evidence indicate a relevant role of infections in the acute exacerbations of CTD-ILD, little information is available regarding the prevalence of infections in chronic CTD-ILD and their possible role in the clinical course. The aim of the present retrospective study was the identification of lung microbial colonization in broncho-alveolar lavage from patients affected by stable CTD-ILD with radiologically defined lung involvement. We demonstrated that 22.7% of patients with CTD-ILD display microbial colonization by Pseudomonas aeruginosa, Haemophilus influenzae, and non-tuberculous mycobacteria. Moreover, these patients display a major radiologic lung involvement, with higher impairment in lung function tests confirmed in a multivariate logistic regression analysis. Overall, the present study provides new information on lung colonization during CTD-ILD and its possible relationship with lung disease progression and severity

Cardiac and Respiratory Influences on Intracranial and Neck Venous Flow, Estimated Using Real-Time Phase-Contrast MRI

The study of brain venous drainage has gained attention due to its hypothesized link with various neurological conditions. Intracranial and neck venous flow rate may be estimated using cardiac-gated cine phase-contrast (PC)-MRI. Although previous studies showed that breathing influences the neck's venous flow, this aspect could not be studied using the conventional segmented PC-MRI since it reconstructs a single cardiac cycle. The advent of real-time PC-MRI has overcome these limitations. Using this technique, we measured the internal jugular veins and superior sagittal sinus flow rates in a group of 16 healthy subjects (12 females, median age of 23 years). Comparing forced-breathing and free-breathing, the average flow rate decreased and the respiratory modulation increased. The flow rate decrement may be due to a vasoreactive response to deep breathing. The respiratory modulation increment is due to the thoracic pump's greater effect during forced breathing compared to free breathing. These results showed that the breathing mode influences the average blood flow and its pulsations. Since effective drainage is fundamental for brain health, rehabilitative studies might use the current setup to investigate if respiratory exercises positively affect clinical variables and venous drainage

COVID-19 and Pregnancy: An Updated Review about Evidence-Based Therapeutic Strategies

The COVID-19 pandemic posed a significant challenge for clinicians in managing pregnant women, who were at high risk of virus transmission and severe illness. While the WHO declared in May 2023 that COVID-19 is no longer a public health emergency, it emphasized that it remains a global health threat. Despite the success of vaccines, the possibility of new pandemic waves due to viral mutations should be considered. Ongoing assessment of the safety and effectiveness of pharmacological therapies is crucial in clinical practice. This narrative review summarizes the evidence-based therapeutic strategies for pregnant women with COVID-19, considering over three years of pandemic experience. The review discusses the safety and effectiveness of various drug regimens (antivirals, anticoagulants, corticosteroids, immunoglobulins, monoclonal antibodies, and therapeutic gases) and procedures (prone positioning and extracorporeal membrane oxygenation). Drugs with contraindications, inefficacy during pregnancy, or unknown adverse effects were excluded from our evaluation. The aim is to provide healthcare professionals with a comprehensive guide for managing pregnant women with COVID-19 based on lessons learned from the pandemic outbreak

Fat Body Mass and Vertebral Fracture Progression in Women With Breast Cancer

Importance Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients receiving AIs and denosumab have not been explored to date.Objectives To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM.Design, Setting, and Participants For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022.Exposure Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy.Main Outcomes and MeasuresVF progression, defined as either new or worsening of preexisting VFs, between the 2 time points.Results Of the 237 patients enrolled (median [range] age, 61 [28-84] years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio [OR], 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression.Conclusions and Relevance The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting

Androgen serum levels in male patients with adrenocortical carcinoma given mitotane therapy: A single center retrospective longitudinal study

ObjectiveHypogonadism is common in male patients with adrenocortical carcinoma (ACC) who are under treatment with mitotane, but the phenomenon is underestimated, and its prevalence has been poorly studied. This single-center retrospective longitudinal study was undertaken to assess the frequency of testosterone deficiency before and after mitotane therapy, the possible mechanism involved, and the relationship between hypogonadism with serum mitotane levels and prognosis.Research design and methodsConsecutive male ACC patients followed at the Medical Oncology of Spedali Civili Hospital in Brescia underwent hormonal assessment to detect testosterone deficiency at baseline and during mitotane therapy.ResultsA total of 24 patients entered the study. Of these patients, 10 (41.7%) already had testosterone deficiency at baseline. During follow-up, total testosterone (TT) showed a biphasic evolution over time with an increase in the first 6 months followed by a subsequent progressive decrease until 36 months. Sex hormone binding globulin (SHBG) progressively increased, and calculated free testosterone (cFT) progressively decreased. Based on cFT evaluation, the proportion of hypogonadic patients progressively increased with a cumulative prevalence of 87.5% over the study course. A negative correlation was observed between serum mitotane levels >14 mg/L and TT and cFT.ConclusionTestosterone deficiency is common in men with ACC prior to mitotane treatment. In addition, this therapy exposes these patients to further elevated risk of hypogonadism that should be promptly detected and counteracted, since it might have a negative impact on quality of life

Measuring respiratory and cardiac influences on blood and cerebrospinal fluid flow with real-time MRI

Background. A link between various pathological conditions and blood and cerebrospinal fluid (CSF) flow alterations has been suggested by numerous studies.1 The blood and CSF dynamics are influenced by many factors, such as posture,2 heart beating, and thoracic pressure changes during respiration.2,3 The blood/CSF can be estimated using phase-contrast (PC) – magnetic resonance imaging (MRI). However, the clinical cardiac-gated cine PC-MRI requires several heartbeats to form the time-resolved flow images covering the entire cardiac cycle, not allowing to assess beat-by-beat variability differences and respiratory-driven flow changes. To overcome these limitations, we recently used a real-time (RT)-PC prototype for the study of blood and CSF flow rate modulations, showing low-frequency oscillations (Mayer waves).4 With the same MRI technique, in the current study we focused on assessing the cardiac and respiratory modulations on the blood and CSF flow rates, and the effects of different respiration modes. Methods. Thirty healthy volunteers (21 females, median age=26 years old, age range= 19-57 years old) were examined with a 3 T scanner. RT-PC sequences (Figure 1) allowed for a quantification of the flow rates of internal carotid arteries (ICAs), internal jugular veins (IJVs), and CSF at the first cervical level. The superior sagittal sinus (SSS) was also studied in 16 subjects.5 The flow rates were estimated with a temporal resolution of 58.5 ms for the blood, and 94 ms for the CSF. Each RT-PC lasted 60 seconds and was repeated three times: while the subject breathed with free (F) breathing, at a constant rate with a normal (PN) or forced (PD) strength. The systolic, diastolic and average flow rates and their power spectral densities were computed. High and very-high frequency peaks were identified on the spectra. Frequencies associated to the identified peaks were compared to the respiratory and cardiac frequencies estimated by a thoracic band and a pulse oximeter. The area under the spectra, normalized by the flow rate variance, was computed in the respiratory and cardiac frequency ranges (0.5 Hz-wide ranges, centered on the cardiac or breathing frequency peaks, respectively). Results. The frequencies associated with the spectral peaks were not significantly different compared to the respiratory and cardiac frequencies, for all regions and breathing modes. The average blood flow rate and the diastolic CSF peak progressively decreased from F to PN to PD breathing, the flow rate variance remained stable, and only the ICAs cross-sectional area decreased. The respiratory modulation increased with PD breathing compared with F and PN, while the cardiac modulations were less predominant for all the structures of interest. Conclusions. Using the RT-PC sequence we showed that the blood and CSF flow rates were modulated at the respiratory and cardiac frequencies. The observed reduced blood flow rate during forced breathing in the arteries and consequently in the extra and intracranial veins are suggestive of compensatory vasoconstriction in response to decreased CO2 blood concentration. Breathing modulation of flow rates was observed both in the extracranial and intracranial compartments, and it was greater during forced breathing than free breathing, due to the greater thoracic pump effect on the flow rates

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries