Systemic and Cardiac Microvascular Dysfunction in Hypertension

Hypertension exerts a profound impact on the microcirculation, causing both structural and functional alterations that contribute to systemic and organ-specific vascular damage. The microcirculation, comprising arterioles, capillaries, and venules with diameters smaller than 20 μm, plays a fundamental role in oxygen delivery, nutrient exchange, and maintaining tissue homeostasis. In the context of hypertension, microvascular remodeling and rarefaction result in reduced vessel density and elasticity, increasing vascular resistance and driving end-organ damage. The pathophysiological mechanisms underlying hypertensive microvascular dysfunction include endothelial dysfunction, oxidative stress, and excessive collagen deposition. These changes impair nitric oxide (NO) bioavailability, increase reactive oxygen species (ROS) production, and promote inflammation and fibrosis. These processes lead to progressive vascular stiffening and dysfunction, with significant implications for multiple organs, including the heart, kidneys, brain, and retina. This review underscores the pivotal role of microvascular dysfunction in hypertension-related complications and highlights the importance of early detection and therapeutic interventions. Strategies aimed at optimizing blood pressure control, improving endothelial function, and targeting oxidative stress and vascular remodeling are critical to mitigating the systemic consequences of hypertensive microvascular damage and reducing the burden of related cardiovascular and renal diseases

Positive single-center randomized trials and subsequent multicenter randomized trials in critically ill patients: a systematic review

Background: It is unclear how often survival benefits observed in single-center randomized controlled trials (sRCTs) involving critically ill patients are confirmed by subsequent multicenter randomized controlled trials (mRCTs). We aimed to perform a systemic literature review of sRCTs with a statistically significant mortality reduction and to evaluate whether subsequent mRCTs confirmed such reduction. Methods: We searched PubMed for sRCTs published in the New England Journal of Medicine, JAMA, or Lancet, from inception until December 31, 2016. We selected studies reporting a statistically significant mortality decrease using any intervention (drug, technique, or strategy) in adult critically ill patients. We then searched for subsequent mRCTs addressing the same research question tested by the sRCT. We compared the concordance of results between sRCTs and mRCTs when any mRCT was available. We registered this systematic review in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023455362). Results: We identified 19 sRCTs reporting a significant mortality reduction in adult critically ill patients. For 16 sRCTs, we identified at least one subsequent mRCT (24 trials in total), while the interventions from three sRCTs have not yet been addressed in a subsequent mRCT. Only one out of 16 sRCTs (6%) was followed by a mRCT replicating a significant mortality reduction; 14 (88%) were followed by mRCTs with no mortality difference. The positive finding of one sRCT (6%) on intensive glycemic control was contradicted by a subsequent mRCT showing a significant mortality increase. Of the 14 sRCTs referenced at least once in international guidelines, six (43%) have since been either removed or suggested against in the most recent versions of relevant guidelines. Conclusion: Mortality reduction shown by sRCTs is typically not replicated by mRCTs. The findings of sRCTs should be considered hypothesis-generating and should not contribute to guidelines

Less is more: We are administering too much protamine in cardiac surgery

Context: Protamine is routinely administered to neutralize the anticlotting effects of heparin, traditionally at a dose of 1 mg for every 100 IU of heparin - a 1:1 ratio protamine sparing effects - but this is based more on experience and practice than literature evidence. The use of Hemostasis Management System (HMS) allows an individualized heparin and protamine titration. This usually results in a decreased protamine dose, thus limiting its side effects, including paradox anticoagulation. Aims: This study aims to assess how the use of HMS allows to reduction of protamine administration while restoring the basal activated clotting time (ACT) at the end of cardiac surgery. Settings and Design: A retrospective observational study in a tertiary care university hospital. Subjects and Methods: We analyzed data from 42 consecutive patients undergoing cardiopulmonary bypass (CPB) for cardiac surgery. For all patients HMS tests were performed before and after CPB, to determine how much heparin was needed to reach target ACT, and how much protamine was needed to reverse it. Results: At the end of cardiopulmonary bypass, 2.2 ± 0.5 mg/kg of protamine was sufficient to reverse heparin effects. The protamine-to-heparin ratio was 0.56:1 over heparin total dose (a 44% reduction) and 0.84:1 over heparin initial dose (a 16% reduction). Conclusion: A lower dose of protamine was sufficient to revert heparin effects after cardiopulmonary bypass. While larger studies are needed to confirm these findings and detect differences in clinically relevant outcomes, the administration of a lower protamine dose is endorsed by current guidelines and may help to avoid the detrimental effects of protamine overdose, including paradox bleeding

Novel Coronavirus disease (Covid-19) in Italian patients: gender differences in presentation and severity

In the first wave of the novel coronavirus (severe acute respiratory syndrome coronavirus 2) infections, Italy experienced a heavy burden of hospital admissions for acute respiratory distress syndromes associated with the novel coronavirus disease (COVID-19). Early evidence suggested that females are less affected than males. This study aimed to assess the gender-related differences in presentation and severity among COVID-19 patients admitted to IRCCS San Raffaele Hospital, Milan, Italy. Materials and Methods: This prospective observational study included all patients admitted to the hospital between February 25 and April 19, 2020, with a positive real-time reverse-transcriptase polymerase chain reaction for COVID-19. The following data were collected: date of admission, gender, age and details of intensive care unit admission and outcomes. Results: A total of 901 patients with COVID-19 were admitted to the hospital and provided consent for the study. Of these, 284 were female (31.5%). The percentage of admitted female patients significantly increased over time (25.9% of all admissions in the first half of the study period vs. 37.1% in the second half; P < 0.001). Females accounted for 14.4% of all COVID-19 intensive care unit admissions. There was no gender-based difference in the overall hospital mortality: 20.1% for females and 19.2% for males (P = 0.8). Conclusions: In our hospital, which was in the epicenter of the first wave of COVID-19 pandemic in Italy, female patients were few, presented late and were less critical than male patients

Gender-gap in randomized clinical trials reporting mortality in the perioperative setting and critical care: 20 years behind the scenes

Background: Women researchers might experience obstacles in academic environments and might be underrepresented in the authorship of articles published in peer-reviewed journals. Material and Methods: This is a cross-sectional analysis of female-led RCTs describing all interventions reducing mortality in critically ill and perioperative patients from 1981 to December 31, 2020. We searched PubMed/MEDLINE and EMBASE with the keywords RCTs and mortality. The gender of the first author was extracted and descriptive analysis was performed including the year of publication, impact factor, country of the first author, and methodological aspects. Results: We analyzed 340 RCTs, of which 42 (12%) were led by female researchers. The presence of women increased from 8% (14/172) until 2010 up to 17% (28/168) in 2010 and beyond. The United States, the United Kingdom, and Brazil were the main countries of origin of female researchers. Women authors conducted mainly single-center and single-nation studies as compared to male authors. The median impact factor of the target journal was 6 (3-27) in women vs. 7 (3-28) in men, with a p-value of 0.67; Critical Care Medicine, JAMA, and The New England Journal of Medicine were the most frequent target journals for both women and men. Conclusion: In the last 40 years, only one out of eight RCTs had a woman as the first author but the presence of women increased up to 17% by 2010 and beyond. The impact factor of publication target journals was high and not different between genders

Gender Gap in Bibliometric Indices of Academic and Non-Academic Italian ICU Physicians

Hirsch-index, better known as, H-index is an important bibliometric index for Italian critical care physicians.   Aim of our study was to collect the H-index of all Italian critical care academic physicians and compare it with the Italian Ministry of University and Research thresholds necessary to be eligible as Professor, and to investigate potential gender disparities in such bibliometric indices.   Materials and Methods. We collected all the names of academic ICU physicians on June 24th, 2023 from the official Italian Ministry of University and Research website. We added non-academic ICU physicians searching on Scopus or among academic physicians’ collaborators. Minimum thresholds to be eligible as Professor were identified through the official Italian Ministry of University and Research website. Median H-index of men and women were compared.   Results. The total number of included physicians was 237 (46 Full Professors, 88 Associate Professors, 79 Researchers and 22 Non-academic physicians). Minimum threshold to be eligible as Associate Professor was 6 and to be eligible as Full Professor was 13. The median H-index in men versus women in every subgroup was: Full Professors (38 [27–49] vs 29 [21–34]), Associate Professors (25 [18–32] vs 22 [18–28]), Researchers (12 [7–21] vs 9 [6–16]) and Non-academic physicians (27 [25–37] vs 26 [25–29]).   Conclusion. Current median H-index of Italian academic ICU physicians is considerably greater than minimum thresholds released by the Italian Ministry of University and Research to be eligible as Professor. Gender gap in bibliometric indices of academic ICU physicians remains

Awake Fiberoptic Intubation Protocols in the Operating Room for Anticipated Difficult Airway: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Awake fiberoptic intubation is one of the recommended strategies for surgical patients with anticipated difficult airway, especially when concurrent difficult ventilation is expected. We performed the first systematic review of randomized controlled trials assessing different protocols for awake fiberoptic intubation in anticipated difficult airway, including studies investigating elective awake fiberoptic intubation for scheduled surgery; randomized controlled trials comparing different methods for performing awake fiberoptic intubation; and adult patients with anticipated difficult airway. We excluded studies in the nonoperating theater settings, randomized controlled trials comparing awake fiberoptic intubation with other techniques, and studies based on simulation. Primary outcomes were success rate and death; secondary outcomes were major adverse events. Thirty-seven randomized controlled trials evaluating 2045 patients and 4 areas were identified: premedication, local anesthesia, sedation, and ancillary techniques to facilitate awake fiberoptic intubation. Quality of evidence was moderate-low and based on small-sampled randomized controlled trials. Overall, 12 of 2045 intubation failures (0.59%) and 7 of 2045 severe adverse events (0.34%) occurred, with no permanent consequences or death. All evaluated methods to achieve local anesthesia performed similarly well. No differences were observed in success rate with different sedatives. Dexmedetomidine resulted in fewer desaturation episodes compared to propofol and opioids with or without midazolam (relative risk, 0.51 [95% CI, 0.28-0.95]; P = .03); occurrence of desaturation was similar with remifentanil versus propofol, while incidence of apnoea was lower with sevoflurane versus propofol (relative risk, 0.43 [95% CI, 0.22-0.81]; P = .01). A high degree of efficacy and safety was observed with minimal differences among different protocols; dexmedetomidine might offer a better safety profile compared to other sedatives

A Randomized Trial of Intravenous Amino Acids for Kidney Protection

Background Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. Methods In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. Results We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P=0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. Conclusions Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI

One-year survival and Quality of Life of first wave COVID-19 invasively ventilated patients in Lombardy, Italy

BACKGROUND: Lombardy was the epicenter of the first coronavirus disease 2019 (COVID-19) outbreak in western countries. The outbreak began in February 2020 and rapidly disseminated throughout the region. ICU beds were vastly insufficient and clinical knowledge of disease was poor at that time. Unfortunately, data on long-term mortality, morbidity, and Quality of Life are scarce and controversial. The aim of this study was to evaluate 1-year survival, Quality of Life, and functional recovery in patients with COVID-19 admitted to Intensive Care Units. METHODS: All COVID-19 patients invasively ventilated and successfully discharged from 3 important academic hospitals in Lombardy were evaluated. Evaluations were performed by qualified medical staff and monitoring over time was performed by telephone call. Functional, cognitive, and psychological outcomes were explored using validated questionnaires. Selected patients were offered a follow-up chest computed tomography (CT) scan. RESULTS: Four hundred twenty-seven patients were invasively ventilated and 268 (63%) were successfully discharged. Out of these 268 patients, 266 (99%) were alive at one year with no patient loss during follow-up. Very severe or severe dyspnea was reported by 7% of patients, while most patients (84%) did not experience dyspnea at rest. A small proportion of patients (17%) reported severe anxiety/depression. Good Quality of Life was reported by 64% of survivors. In patients complaining of dyspnea on exertion, fibrotic-like changes were observed at chest CT scans in 32/37 (86%) and 7/11 (63%) patients who underwent CT at 3 months and 1 year, respectively. CONCLUSIONS: COVID-19 patients discharged from the hospital after invasive ventilation had excellent one-year survival and good overall recovery and Quality of Life

A Placebo-Controlled Trial of PCI for Stable Angina

To the Editor: In the editorial accompanying the article by Rajkumar and colleagues (Dec. 21 issue)(1) on the results of the ORBITA-2 trial involving the use of percutaneous coronary intervention (PCI) in patients with stable angina, White(2) begins with a flawed premise: "The primary aim of treating patients with stable angina is to decrease symptoms and improve quality of life." That is not the primary aim of treating these patients. Relieving angina is important, but the real priority in the management of stable angina is the provision of appropriate medical therapy to reduce the risk of myocardial infarction and sudden . .