Global Current Practices of Ventilatory Support Management in COVID-19 Patients: An International Survey.

BACKGROUND: As the global outbreak of COVID-19 continues to ravage the world, it is important to understand how frontline clinicians manage ventilatory support and the various limiting factors. METHODS: An online survey composed of 32 questions was developed and validated by an international expert panel. RESULTS: Overall, 502 respondents from 40 countries across six continents completed the survey. The mean number (±SD) of ICU beds was 64 ± 84. The most popular initial diagnostic tools used for treatment initiation were arterial blood gas (48%) and clinical presentation (37.5%), while the national COVID-19 guidelines were the most used (61.2%). High flow nasal cannula (HFNC) (53.8%), non-invasive ventilation (NIV) (47%), and invasive mechanical ventilation (IMV) (92%) were mostly used for mild, moderate, and severe COVID-19 cases, respectively. However, only 38.8%, 56.6% and 82.9% of the respondents had standard protocols for HFNC, NIV, and IMV, respectively. The most frequently used modes of IMV and NIV were volume control (VC) (36.1%) and continuous positive airway pressure/pressure support (CPAP/PS) (40.6%). About 54% of the respondents did not adhere to the recommended, regular ventilator check interval. The majority of the respondents (85.7%) used proning with IMV, with 48.4% using it for 12-16 hours, and 46.2% had tried awake proning in combination with HFNC or NIV. Increased staff workload (45.02%), lack of trained staff (44.22%) and shortage of personal protective equipment (PPE) (42.63%) were the main barriers to COVID-19 management. CONCLUSION: Our results show that general clinical practices involving ventilatory support were highly heterogeneous, with limited use of standard protocols and most frontline clinicians depending on isolated and varied management guidelines. We found increased staff workload, lack of trained staff and shortage of PPE to be the main limiting factors affecting global COVID-19 ventilatory support management.

Upper and lower full arch dental reconstruction with implant supported overdentures: a case study.

STATEMENT OF PROBLEM: In clinical situations where implant placement in the maxilla is prohibited due to the lack of available bone, more invasive techniques such as autogenous bone grafting and sinus augmentation are often off-putting to patients due to the added expense, risk and morbidity. Purpose of treatment: The intention of this treatment was to dentally restore a patient with a severely resorbed edentulous maxilla, without the use of any grafting techniques. METHODS: Under local anaesthetic, five implants were placed in the patient's maxilla using the combined techniques of alveolar ridge-splitting and a Summer's lift. The crest of the alveolus was dissected bilaterally with a fine rotary disc. A combination of osteotomes and bone spreaders were then used to create the individual osteotomies. In the most distal site on the right side, the floor of the maxillary sinus was tapped up to facilitate implant placement. All implants were submerged under the gum for six months to allow them to ossteointegrate. Restorative stages were then completed. RESULTS: At six months, all five maxillary implants had successfully integrated. The maxilla also showed marked expansion where the alveolus had been dissected and bone had healed between the separated buccal and palatal plates. The final restoration was a metal-framed overdenture attached to a milled titanium bar supported on five implants. CONCLUSION: In this single case study, a patient's atrophic, edentulous maxilla was successfully restored without grafting techniques. The overdenture has been in trouble-free function for two years.

Implant placement in the aesthetic zone following an autogenous bone graft from an intraoral site: a case study.

AIMS: In the front of the mouth, the treatment of such a bony defect carries the risk of a poor aesthetic outcome. High patient expectations, combined with the difficulty of recreating a large mass of viable bone in which a dental implant will be biomechanically stable is a real challenge. PURPOSE OF TREATMENT: The intention of this treatment was to replace the patient's chronically infected upper right incisor with a dental implant that was both biomechanically and aesthetically stable for the long term. METHOD: Four months after extraction of the upper right central incisor, under local anaesthetic, a bone block was harvested from the right retromolar area of the patient's mandible and grafted into the defect. This was secured with a single bone screw. Small deficiencies between the block and the host site were filled in using bovine derived particulate bone (Bio Oss, Geistlich Biomaterials, Wolhuser, Germany). A resorbable porcine derived membrane (Bio-Gide, Geistlich Biomaterials, Wolhuser, Germany), held in position by two bone tacks (Frios, Friadent, Mannheim, Germany), was used to stabilse the graft. Following close clinical and radiographic monitoring of graft maturation, the bone screw was removed at three months and one week later the implant placed. A bone level impression was taken at surgery, and the implant left submerged for four months before exposure and abutment connection. After a further period of two months to facilitate soft tissue contouring the definitive crown was cemented. CONCLUSION: The implant tooth has been in trouble free function for eighteen months. In that period, the marginal bone levels and gingival margin around the implant have remained stable and aesthetically satisfactory.

Aspirin-associated iron loss as an anticancer mechanism.

A consensus view has emerged favoring an anticancer effect of long-term aspirin use. Aspirin-induced loss of stored iron from chronic gastrointestinal bleeding is proposed as a mechanism underlying this beneficial effect. In iron depletion, less iron may be available for carcinogenesis through free-radical mediated mechanisms and for promotion of tumor growth. Low-dose aspirin increases gastrointestinal losses of transfused radiolabeled autologous red cells. Observational studies report lower serum ferritin values with regular aspirin use. A protective effect of induced iron reduction against cancer mortality has been confirmed in a recent trial (FeAST) with subjects randomized to iron reduction or observation. Serum ferritin reductions in the FeAST trial were within conventionally normal reference ranges and were quantitatively similar to ferritin reductions in observational studies in regular aspirin users. Delayed anticancer effects of aspirin are compatible with the proposed mechanism, as continual microbleeding has a gradual cumulative effect on stored iron.

Iron in arterial plaque: modifiable risk factor for atherosclerosis.

It has been proposed that iron depletion protects against cardiovascular disease. There is increasing evidence that one mechanism for this protection may involve a reduction in iron levels within atherosclerotic plaque. Large increases in iron concentration are seen in human atherosclerotic lesions in comparison to levels in healthy arterial tissue. In animal models, depletion of lesion iron levels in vivo by phlebotomy, systemic iron chelation treatment or dietary iron restriction reduces lesion size and/or increases plaque stability. A number of factors associated with increased arterial disease or increased cardiovascular events is also associated with increased plaque iron. In rats, infusion of angiotensin II increases ferritin levels and arterial thickness which are reversed by treatment with the iron chelator deferoxamine. In humans, a polymorphism for haptoglobin associated with increased cardiovascular disease is also characterized by increased lesional iron. Heme oxygenase 1 (HO1) is an important component of the system for mobilization of iron from macrophages. Human HO1 promoter polymorphisms causing weaker upregulation of the enzyme are associated with increased cardiovascular disease and increased serum ferritin. Increased cardiovascular disease associated with inflammation may be in part caused by elevated hepcidin levels that promote retention of iron within plaque macrophages. Defective retention of iron within arterial macrophages in genetic hemochromatosis may explain why there is little evidence of increased atherosclerosis in this disorder despite systemic iron overload. The reviewed findings support the concept that arterial plaque iron is a modifiable risk factor for atherogenesis.

Overexpression of transferrin receptor and ferritin related to clinical symptoms and destabilization of human carotid plaques.

Accumulation of tissue iron has been implicated in development of atherosclerotic lesions mainly because of increased iron-catalyzed oxidative injury. However, it remains unknown whether cellular iron import and storage in human atheroma are related to human atheroma development. We found that transferrin receptor 1 (TfR1), a major iron importer, is highly expressed in foamy macrophages and some smooth muscle cells in intimal lesions of human carotid atheroma, mainly in cytoplasmic accumulation patterns. In 52 human carotid atherosclerotic lesions, TfR1 expression was positively correlated with macrophage infiltration, ectopic lysosomal cathepsin L, and ferritin expression. Highly expressed TfR1 and ferritin in CD68-positive macrophages were significantly associated with development and severity of human carotid plaques, smoking, and patient's symptoms. The findings suggest that pathologic macrophage iron metabolism may contribute to vulnerability of human atheroma, established risk factors, and their clinical symptoms. The cytoplasmic overexpression of TfR1 may be the result of lysosomal dysfunction and ectopic accumulation of lysosomal cathepsin L caused by atheroma-relevant lipids in atherogenesis.

[Current status of the iron hypothesis of cardiovascular diseases]. / La cosiddetta "iron hypothesis": un persistente stato di deplezione di ferro può proteggere contro le malattie cardiovascolari?

More than 25 years ago, the iron hypothesis proposed that a state of sustained iron depletion or mild iron deficiency exerts a primary protective action against ischemic heart disease. Iron depletion leads to a decreased availability of redox-active iron in vivo. The amount of free iron available at sites of oxidative or inflammatory injury appears to be a function of the stored iron level. Depletion of iron levels by phlebotomy, systemic iron chelation treatment or dietary iron restriction reduce atherosclerotic lesion size and increase plaque stability. In homozygous hemochromatosis there is commonly a defect that inhibits iron retention in macrophages. This defect may explain why atherosclerotic lesions appear to be less prevalent in this disorder. Findings of the "FeAST" trial have been recently reported. The trial assessed the potential benefit of mild iron reduction therapy in secondary prevention of cardiovascular disease. It was therefore not a fully valid test of primary prevention as postulated by the iron hypothesis. However, although no overall statistically significant cardiovascular benefit was found, in the youngest quartile at entry there were highly significant reductions in all cause mortality and in combined death plus non-fatal myocardial infarction and stroke in association with iron reduction therapy. The FeAST trial adds urgency to the initiation of new studies to assess the impact of maintenance of complete iron depletion in the primary prevention of cardiovascular diseases.

Macrophage iron, hepcidin, and atherosclerotic plaque stability.

Hepcidin has emerged as the key hormone in the regulation of iron balance and recycling. Elevated levels increase iron in macrophages and inhibit gastrointestinal iron uptake. The physiology of hepcidin suggests an additional mechanism by which iron depletion could protect against atherosclerotic lesion progression. Without hepcidin, macrophages retain less iron. Very low hepcidin levels occur in iron deficiency anemia and also in homozygous hemochromatosis. There is defective retention of iron in macrophages in hemochromatosis and also evidently no increase in atherosclerosis in this disorder. In normal subjects with intact hepcidin responses, atherosclerotic plaque has been reported to have roughly an order of magnitude higher iron concentration than that in healthy arterial wall. Hepcidin may promote plaque destabilization by preventing iron mobilization from macrophages within atherosclerotic lesions; the absence of this mobilization may result in increased cellular iron loads, lipid peroxidation, and progression to foam cells. Marked downregulation of hepcidin (e.g., by induction of iron deficiency anemia) could accelerate iron loss from intralesional macrophages. It is proposed that the minimally proatherogenic level of hepcidin is near the low levels associated with iron deficiency anemia or homozygous hemochromatosis. Induced iron deficiency anemia intensely mobilizes macrophage iron throughout the body to support erythropoiesis. Macrophage iron in the interior of atherosclerotic plaques is not exempt from this process. Decreases in both intralesional iron and lesion size by systemic iron reduction have been shown in animal studies. It remains to be confirmed in humans that a period of systemic iron depletion can decrease lesion size and increase lesion stability as demonstrated in animal studies. The proposed effects of hepcidin and iron in plaque progression offer an explanation of the paradox of no increase in atherosclerosis in patients with hemochromatosis despite a key role of iron in atherogenesis in normal subjects.