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Keywords: Coronavirus, COVID-19, Angiotensin II, ACE2, RAAS

Background In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. Methods We measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes. Results Median baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30–676.00 pg/mL] vs 42 pg/mL [IQR 30.46–87.34 pg/mL] in controls; P  <  0.0001) and median ANG I/II ratio (1.63 [IQR 0.98–5.25] vs 0.4 [IQR 0.28–0.64] in controls; P  <  0.0001) were elevated, whereas median ANG II levels were similar (84 pg/mL [IQR 23.85–299.50 pg/mL] vs 97 pg/mL [IQR 35.27–181.01 pg/mL] in controls; P  = 0.9895). At baseline, patients with a ratio above the median (≥1.63) had higher ANG I levels ( P  <  0.0001), lower ANG II levels ( P  <  0.0001), higher albumin concentrations ( P  = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors ( P  <  0.00001), and they received a higher norepinephrine-equivalent dose ( P  = 0.003). In the placebo group, a baseline ANG I/II ratio <1.63 was associated with improved survival (hazard ratio 0.56; 95% confidence interval 0.36–0.88; P  = 0.01) on unadjusted analyses. Conclusions Patients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction. Trial registration ClinicalTrials.gov identifier NCT02338843 . Registered 14 January 2015.

The globalization of medical research and global health’s increasing popularity worldwide have resulted in greater geographic, ethnic, and socioeconomic diversity of studies published in the scientific literature. Yet the geographic distribution, authorship representation, and subject trends among Low-/Low-Middle-Income Country (LIC/LMIC)-based scientific publications remain largely unknown. This analysis assesses these gaps in knowledge. We performed a comprehensive bibliometric analysis of all scientific articles published between January 2014 and June 2016 in the four most prominent general medicine and five most prominent general global health journals based on impact factor. The African region, containing 24% of the global LIC/LMIC population, accounted for 49.9% of all publications. Corresponding authors with either exclusive or joint appointment to a LIC/ LMIC institution were present in 26.2% of all included articles. Over one-quarter (28.8%) of all publications did not list a local author. Nearly two-thirds (62.1%) of articles published in global health journals and roughly half (52.4%) in general medicine journals involved infectious diseases. Non-HIV infectious disease studies were by far the most frequent subject areas across all journals. The trends identified in this study may help to inform the evolution and prioritization of future research efforts, thereby allowing global health to remain truly global.

Background Circulatory shock is a common syndrome with a high mortality and limited therapeutic options. Despite its discovery and use in clinical and experimental settings more than a half-century ago, angiotensin II (Ang II) has only been recently evaluated as a vasopressor in distributive shock. We examined existing literature for associations between Ang II and the resolution of circulatory shock. Methods We searched PubMed, MEDLINE, Ovid, and Embase to identify all English literature accounts of intravenous Ang II in humans for the treatment of shock (systolic blood pressure [SBP] ≤ 90 mmHg or a mean arterial pressure [MAP] ≤ 65 mmHg), and hand-searched the references of extracted papers for further studies meeting inclusion criteria. Of 3743 articles identified, 24 studies including 353 patients met inclusion criteria. Complete data existed for 276 patients. Extracted data included study type, publication year, demographics, type of shock, dosing of Ang II or other vasoactive medications, and changes in BP, lactate, and urine output. BP effects were grouped according to type of shock, with additional analyses completed for patients with absent blood pressure. Shock was distributive ( n  = 225), cardiogenic ( n  = 38), or from other causes ( n  = 90). Blood pressure as absent in 18 patients. Results For the 276 patients with complete data, MAP rose by 23.4% from 63.3 mmHg to 78.1 mmHg in response to Ang II (dose range: 15 ng/kg/min to 60 mcg/min). SBP rose by 125.2% from 56.9 mmHg to 128.2 mmHg (dose range: 0.2 mcg/min to a 1500 mcg bolus). A total of 271 patients with complete data were determined to exhibit a BP effect which was directly associated with Ang II. Subgroups (patients with cardiogenic, septic, and other types of shock) exhibited similar increases in BP. In patients with absent BP, deemed to be cardiac arrest, return of spontaneous circulation (ROSC) was achieved, and BP increased by an average of 107.3 mmHg in 11 of 18 patients. The remaining seven patients with cardiac arrest did not respond. Conclusions Intravenous Ang II is associated with increased BP in patients with cardiogenic, distributive, and unclassified shock. A role may exist for Ang II in restoring circulation in cardiac arrest.

Rapid identification of potentially life-threatening blood stream infections (BSI) improves clinical outcomes, yet conventional blood culture (BC) identification methods require ~24–72 hours of liquid culture, plus 24–48 hours to generate single colonies on solid media suitable for identification by mass spectrometry (MS). Newer rapid centrifugation techniques, such as the Bruker MBT-Sepsityper ® IVD, replace culturing on solid media and expedite the diagnosis of BCs but frequently demonstrate reduced sensitivity for identifying clinically significant Gram-positive bacterial or fungal infections. This study introduces a protocol that utilises the broad-range binding properties of an engineered version of mannose-binding lectin linked to the Fc portion of immunoglobulin (FcMBL) to capture and enrich pathogens combined with matrix-assisted laser desorption-ionisation time-of-flight (MALDI-TOF) MS for enhanced infection identification in BCs. The FcMBL method identified 94.1% (64 of 68) of clinical BCs processed, with a high sensitivity for both Gram-negative and Gram-positive bacteria (94.7 and 93.2%, respectively). The FcMBL method identified more patient positive BCs than the Sepsityper ® (25 of 25 vs 17 of 25), notably with 100% (3/3) sensitivity for clinical candidemia, compared to only 33% (1/3) for the Sepsityper ® . Additionally, during inoculation experiments, the FcMBL method demonstrated a greater sensitivity, identifying 100% (24/24) of candida to genus level and 9/24 (37.5%) top species level compared to 70.8% (17/24) to genus and 6/24 to species (25%) using the Sepsityper ® . This study demonstrates that capture and enrichment of samples using magnetic FcMBL-conjugated beads is superior to rapid centrifugation methods for identification of BCs by MALDI-TOF MS. Deploying the FcMBL method therefore offers potential clinical benefits in sensitivity and reduced turnaround times for BC diagnosis compared to the standard Sepsityper ® kit, especially for fungal diagnosis.

Critical illness affects health systems globally, but low- and middle-income countries (LMICs) bear a disproportionate burden. Due to a paucity of data, the capacity to care for critically ill patients in LMICs is largely unknown. Haiti has the lowest health indices in the Western Hemisphere. In this study, we report results of the first known nationwide survey of critical care capacity in Haiti. Nationwide, cross-sectional survey of Haitian hospitals in 2017-2018. Haiti. All Haitian health facilities with at least six hospital beds. Electronic- and paper-based survey. Of 51 health facilities identified, 39 (76.5%) from all ten Haitian administrative departments completed the survey, reporting 124 reported ICU beds nationally. Of facilities without an ICU, 20 (83.3%) care for critically ill patients in the emergency department. There is capacity to ventilate 62 patients nationally within ICUs and six patients outside of the ICU. One-third of facilities with ICUs report formal critical care training for their physicians. Only five facilities met criteria for a Level 1 ICU as defined by the World Federation of Societies of Intensive and Critical Care Medicine. Self-identified barriers to providing more effective critical care services include lack of physical space for critically ill patients, lack of equipment, and few formally trained physicians and nurses. Despite a high demand for critical care services in Haiti, current capacity remains insufficient to meet need. A significant amount of critical care in Haiti is provided outside of the ICU, highlighting the important overlap between emergency and critical care medicine in LMICs. Many ICUs in Haiti lack basic components for critical care delivery. Streamlining critical care services through protocol development, education, and training may improve important clinical outcomes.

Septic shock management in the cardiac intensive care unit (CICU) is challenging due to the complex interaction of pathophysiology between vasodilatory and cardiogenic shock, complicating how to optimally deploy fluid resuscitation, vasopressors, and mechanical circulatory support devices. Because mixed shock portends high mortality and morbidity, familiarity with quality, contemporary clinical evidence surrounding available therapeutic tools is needed to address the resultant wide range of complications that can arise. This review integrates pathophysiology principles and clinical recommendations to provide an organized, topic-based review of the nuanced intricacies of managing sepsis in the CICU.

In response to the 2010 earthquake and subsequent cholera epidemic, St Luke's Medical Center was established in Port-au-Prince, Haiti. Here, we describe its inception and evolution to include an intensive care unit and two operating rooms, as well as the staffing, training and experiential learning activities, which helped St Luke's become a sustainable surgical resource. We describe a three-phase model for establishing a sustainable surgical centre in Haiti (build facility and acquire equipment; train staff and perform surgeries; provide continued education and expansion including regular specialist trips) and we report a progressive increase in the number and complexity of cases performed by all-Haitian staff from 2012 to 2022. The results are generalised in the context of the 'delay framework' to global health along with a discussion of the application of this three-phase model to resource-limited environments. We conclude with a brief description of the formation of a remote surgical centre in Port-Salut, an unforeseen benefit of local competence and independence. Establishing sustainable and collaborative surgery centres operated by local staff accelerates the ability of resource-limited countries to meet high surgical burdens.

Abstract Despite the low risk of peripherally inserted central catheter (PICC) insertion-related bleeding, the practice of administering prophylactic platelets varies greatly. Limiting unnecessary blood product transfusions reduces transfusion-related adverse events, financial cost, and delays in care. We assessed the impact of lowering prophylactic platelet administration threshold on blood product utilization patterns and bleeding events. This quasi-experimental study was conducted in an urban academic tertiary medical center. The study population included patients with platelet counts ≥ 10,000/µL and < 50,000/µL undergoing PICC placement in 2018 and 2019 when the minimum platelet thresholds were 50,000/µL and 10,000/µL, respectively. The primary outcome was blood product utilization and the secondary outcome was PICC insertion-related bleeding complications. Thirty-five patients using the 10,000/µL (10 K) platelet threshold and 46 patients using the 50,000/µL (50 K) platelet threshold were enrolled. The 50 K group received more platelets before PICC insertion (0.870 ± 0.885 and 0.143 ± 0.430 pools of platelets-per-person, p < 0.001). No patients experienced clinically significant bleeding. Immediately following PICC insertion, minor bleeding occurred in five patients (two [4.3%] and three [8.6%] in the 50 K and 10 K groups, respectively). Bleeding rates between the two cohorts did not differ (p = 0.647). Lowering the minimum platelet threshold from 50,000/µL to 10,000/µL resulted in less prophylactic platelet and total blood product administration with no appreciable difference in PICC insertion-related bleeding.