Risk factors and interventions associated with mortality or survival in adult COVID-19 patients admitted to critical care: a systematic review and meta-analysis

Patients with confirmed COVID-19 admitted to intensive care units have a high mortality rate, which appears to be associated with increasing age, male sex, smoking history, hypertension and diabetes mellitus. Methods: A systematic review to determine risk factors and interventions associated with mortality/survival in adult patients admitted to an intensive care unit (ICU) with confirmed COVID-19/SARS-CoV-2 infection. The protocol was registered with PROSPERO (CRD42020181185).Results: The search identified 483 abstracts between 1 January and 7 April 2020, of which nine studies were included in the final review. Only one study was of low bias. Advanced age (odds ratio [OR] 11.99, 95% confidence interval [CI] 5.35­18.62) and a history of hypertension were associated with mortality (OR 4.17, 95% CI 2.90­5.99). Sex was not associated with mortality. There was insufficient data to assess the association between other comorbidities, laboratory results or critical care risk indices and mortality.The critical care interventions of mechanical ventilation (OR 6.25, 95% CI 0.75­51.93), prone positioning during ventilation (OR 2.06, 95% CI 0.20­21.72), and extracorporeal membrane oxygenation (ECMO) (OR 8.00, 95% CI 0.69, 92.33) were not associated with mortality. The sample size was insufficient to conclusively determine the association between these interventions and ICUmortality. The need for inotropes or vasopressors was associated with mortality (OR 6.36, 95% CI 1.89­21.36). Conclusion: The studies provided little granular data to inform risk stratification or prognostication of patients requiring intensive

Plasmodesmata-located protein overexpression negatively impacts the manifestation of systemic acquired resistance and the long-distance movement of Defective in Induced Resistance1 in Arabidopsis.

Systemic acquired resistance (SAR) is a plant defence response that provides immunity to distant uninfected leaves after an initial localised infection. The lipid transfer protein (LTP) Defective in Induced Resistance1 (DIR1) is an essential component of SAR that moves from induced to distant leaves following a SAR-inducing local infection. To understand how DIR1 is transported to distant leaves during SAR, we analysed DIR1 movement in transgenic Arabidopsis lines with reduced cell-to-cell movement caused by the overexpression of Plasmodesmata-Located Proteins PDLP1 and PDLP5. These PDLP-overexpressing lines were defective for SAR, and DIR1 antibody signals were not observed in phloem sap-enriched petiole exudates collected from distant leaves. Our data support the idea that cell-to-cell movement of DIR1 through plasmodesmata is important during long-distance SAR signalling in Arabidopsis.

Guideline for the diagnosis and management of multiple sclerosis: a Southern African perspective.

Before making a diagnosis of multiple sclerosis (MS), it is imperative that alternative diagnoses are considered and excluded. This is particularly important in South Africa, which is a moderate prevalence MS area, has a high burden of neurological infections and where the majority of the people are black - an ethnic group that has a very low frequency of MS. Before applying diagnostic criteria, there should be no better explanation for the patient's presentation. This guideline, written on behalf of the Multiple Sclerosis Society of South Africa, aims to assist in the diagnosis and treatment of MS in Southern Africa. 

Critical comparison between modified Monier-Williams and electrochemical methods to determine sulfite in aqueous solutions.

In the present work, known concentration of sulfite aqueous solutions in the presence and absence of gallic acid was measured to corroborate the validity of modified Monier-Williams method. Free and bound-sulfite was estimated by differential pulse voltammetry. To our surprise, the modified Monier-Williams method (also known as aspiration method) showed to be very inaccurate for free-sulfite, although suitable for bound-sulfite determination. The differential pulse approach, using the standard addition method and a correction coefficient, proved to be swift, cheap, and very precise and accurate.

Characterization of a neutral polysaccharide with antioxidant capacity from red wine.

A neutral fraction (PS-SI) (0.3g/L) with MW of 74kDa, which contained galactose, arabinose, mannose, and glucose in the molar ratio of 1.0:0.6:0.4:0.2 was obtained by treatment of the whole polysaccharide extracted from red wine with cetrimide, followed by gel permeation chromatography. Spectroscopic and methylation analyses indicated that PS-SI is a mixture of neutral polysaccharides, consisting mainly of beta (1-->3)-linked galactopyranosyl residues, with side chains of galactopyranosyl residues at positions O-6. Arabinofuranosyl residues linked alpha (1-->5), alpha-mannopyranosyl and glucosyl residues appear to be components of different polysaccharides. The in vitro antioxidant capacity of fractions of wine polysaccharide was studied by hydroxyl radical scavenging and ORAC assays. Fraction PS-SI presented the strongest effect on hydroxyl radicals (IC(50)=0.21).

Cytomegalovirus antiviral resistance associated with treatment induced UL97 (protein kinase) and UL54 (DNA polymerase) mutations.

HCMV-related illness due to infections with antiviral resistant virus was verified by phenotypic and genotypic assays in 17% (8/47) of high-risk immunocompromised Australian patients. Selective PCR-sequencing of UL97 (protein kinase; PK) and UL54 (DNA polymerase; DNApol) regions important for antiviral sensitivity, identified the majority (6/8) of resistant strains through detection of mutations known to confer antiviral resistance. Additionally, eight UL54 (DNApol) mutations (N408K, T691S, A692V, S695T, L737M, A834P, V955I, and A972V) of unknown phenotype were identified in six specimens from patients with clinical evidence of antiviral resistant infections. One isolate was resistant to ganciclovir (GCV) and another resistant to PFA on phenotypic testing where mutations in UL97 (PK) or UL54 (DNApol) were not detected, suggesting a loss of correlation between phenotype and genotype. Selective PCR-sequencing of UL97 (PK) and UL54 (DNApol) provided rapid and comprehensive results, but missed some resistance detected by phenotypic assays. A combination of phenotypic and genotypic assays is recommended for complete analysis of CMV antiviral resistance, as well as further definition of the clinical relationship between novel UL54 (DNApol) mutations and antiviral resistance.

In vitro effects of thawing fresh-frozen plasma at various temperatures.

Thawing fresh-frozen plasma (FFP) in South Africa is uncontrolled because the plasma is issued frozen from the blood bank and thawing techniques and temperatures are at the discretion of the clinician. Following anecdotal reports of disseminated intravascular coagulation (DIC) developing in patients who received FFP thawed in an uncontrolled manner, the effects of various thawing temperatures on coagulation parameters were studied. Fifteen adult units of FFP were each divided into 4 satellite units by the South African Blood Transfusion Service before freezing at -25 degrees C. These bags were then defrosted in a waterbath at 22 degrees C, 37 degrees C, 45 degrees C and 60 degrees C, respectively, and removed as soon as they had thawed. Samples were collected for measurement of International Normalized Ratio (INR), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, and D-dimers. These tests were done according to standard operating procedures. FFP samples were also used in place of agonist in platelet aggregation studies to assess whether the FFP could induce platelet aggregation. Results were analyzed with the percentage similarity model. Using this method the percentage similarity (%sim) of each bag thawed at each temperature with the same donor's bag thawed at 37 degrees C was calculated. The mean, standard deviation, and percentage coefficient of variation of the percentage similarities were then derived. Data sets were also compared using the Wilcoxon test. The fibrinogen values remained stable at 22-45 degrees C (%sim = 97-99%) while there was a significant decrease in fibrinogen levels at 60 degrees C compared with 37 degrees C (p<0.001, %sim = 75%). INR and PTT values were highest in the bags thawed at 60 degrees C (%sim = 114% and 110%, respectively) with the difference between the INR levels at 60 degrees C compared with 37 degrees C showing statistical significance (p<0.05). D-dimers were high at all temperatures tested with widely ranging results at each temperature. The FFP did not induce platelet aggregation at any of the thawing temperatures. In summary, INR and PTT values increase at a thawing temperature of 60 degrees C compared with 37 degrees C. D-dimers are elevated in thawed FFP. Fibrinogen levels are markedly decreased in FFP thawed at 60 degrees C compared with that thawed at 37 degrees C. FFP should be thawed at 37 degrees C in a strictly controlled environment.

Endovenous laser treatment of the incompetent greater saphenous vein.

PURPOSE: To assess the safety and preliminary efficacy of endovenous laser treatment (EVLT), a novel percutaneous technique for occlusion of the incompetent greater saphenous vein (GSV). MATERIALS AND METHODS: Ninety GSVs in 84 patients with reflux at the saphenofemoral junction (SFJ) into the GSV were treated endovenously with pulses of laser energy and evaluated in a prospective, nonrandomized, consecutive enrollment multicenter study. Patients were evaluated at 1 week and at 1, 3, 6, and 9 months to determine efficacy and complications. RESULTS: Eighty-seven of 90 GSVs (97%) were closed 1 week after initial treatment with endovenous laser. The remaining three GSVs were closed after repeat treatment. Eighty-nine of 90 GSVs (99%) remained closed for as long as 9 months according to serial duplex ultrasonography. Sonographic evaluation demonstrated 73% reduction in GSV diameter at 6 months (61 patients) and 81% reduction in GSV diameter at 9 months (26 patients) after EVLT. One patient developed a transient localized skin paresthesia. There have been no other minor or major complications. CONCLUSIONS: EVLT of the incompetent GSV appears to be an extremely safe technique that yields impressive short-term results. Long-term follow-up is awaited.

[Sandimmun vs Neoral, comparison between two types of cyclosporine in patients with kidney transplantation]. / Sandimmun vs Neoral: comparación entre dos tipos de Ciclosporina en pacientes con trasplante de riñón.

We present a comparative trial between Sandimmun, the original cyclosporine presentation, and a modified one, called Neoral, in microemulsion, to increase the blood absortion and stability of the product. We built for each product, an absorption kinetic curve and we applied it to three patients with stable renal function, using the same dosage that was used for ciclosporine. We observed a greater absorption and stability in the blood levels of Neoral. We analyzed hundred blood samples in 25 patients and we found a higher level of this product; this lead us to make possible that in 72% of the patients we could diminish the daily dosis in 5 to 10%. The patient's renal function was stable and no complications or secondary effects were present with Neoral.

Sandimmun vs Neoral: comparación entre dos tipos de Ciclosporina en pacientes con trasplante de riñón / Sandimmun vs Neoral: comparison between two types of cyclosporine in patients with kidney transplantation

We present a comparative trial between Sandimmun, the original cyclosporine presentation, and a modified one, called Neoral, in microemulsion, to increase the blood absortion and stability of the product. We built for each product, an absorption kinetic curve and we applied it to three patients with stable renal function, using the same dosage that was used for ciclosporine. We observed a greater absorption and stability in the blood levels of Neoral. We analyzed hundred blood samples in 25 patients and we found a higher level of this product; this lead us to make possible that in 72% of the patients we could diminish the daily dosis in 5 to 10%. The patient's renal function was stable and no complications or secondary effects were present with Neoral.

[Immunologic profile of patients with renal transplantation in Panama]. / Perfil inmunologico del paciente con trasplante renal en Panama.

We are presenting the immunologic pattern of 100 patients with kidney transplant made from 1990-2000 at CHM CSS Dr.AAM. Eighty nine were alive related donors. Most of them were from blood group O, donors and receptors. They came from Panama, Chiriqui and Colon. Many of the donors were siblings. The grades of compatibility in frequency were D, C, A & B. For locus HLA-A the most common gen was A2 for transplanted patients and for the rest of the Panamanian population is A24. For the locus HLA-B were B35 and B38 respectively and for the locus HLA-C the most common gen was C4, and C3 for the rest of the population.

Accuracy of paramedic identification of stroke and transient ischemic attack in the field.

PURPOSE: To determine the accuracy of acute stroke identification by paramedics in an urban emergency medical services system. METHODS: Retrospective chart review of all patient encounters by paramedics resulting in transport to two university hospitals during a six-month period. Subjects were identified by paramedic coding of stroke/transient ischemic attach (TIA) or final hospital discharge ICD-9 diagnosis of acute stroke and TIA. The sensitivity and positive predictive value for paramedic identification of stroke were calculated, and the time intervals from symptom onset to various points along the patients' prehospital and hospital courses were identified. RESULTS: Ninety-six patients were identified, of whom 81 met the diagnosis of acute stroke or TIA. Paramedics identified 49 of these 81 patients (sensitivity 61%). Fifteen patients were identified by paramedics as having a stroke when the patient ultimately had a different diagnosis (positive predictive value 77%) Patients or their families waited on average 2.5 +/- 3.6 (SD) hours before accessing 911, and a mean of 5.1 +/- 4.0 (SD) hours elapsed from symptom onset until head imaging studies were obtained. CONCLUSION: Paramedics in San Francisco County were correct three-fourths of the time when their documentation listed patients as having stroke/TIA. However, they did not identify 39% of stroke victims, a patient population who may benefit from urgent therapy. A substantial period elapses before stroke victims access 911. This highlights the need to develop an educational program for the community at risk for stroke, and another for paramedics directed toward more accurate identification of acute stroke victims.

Immunological markers of disease progression in patients infected with the human immunodeficiency virus.

Identification of inexpensive and technically simple immunological tests useful in predicting the progression to AIDS in human immunodeficiency virus (HIV)-infected patients would be especially welcome in developing countries, in which 80% of HIV-infected patients reside and health budgets are low. In the current study, we evaluated CD4+ and total lymphocyte counts and the concentrations in serum of beta 2-microglobulin, p24 antigen, and immunoglobulin A (IgA) as predictors of disease progression in 74 Panamanian HIV-positive patients and 50 HIV-negative healthy individuals. Total lymphocyte and CD4(+)-cell counts for AIDS patients (1,451 +/- 811 cells/microliters, P < 0.001, and 238 +/- 392 cells/microliters, P < 0.0001, respectively and asymptomatic patients (2,393 +/- 664 cells/microliters, P > 0.05, and 784 +/- 475 cells/microliters, P < 0.001, respectively) were lower than those observed for healthy subjects (2,596 +/- 631 cells/microliters and 1,120 +/- 296 cells/microliters, respectively). The levels of beta 2-microglobulin and IgA in serum were significantly elevated in patients with AIDS (5.7 +/- 3.6mg/liter, P < 0.001, and 541 +/- 265 mg/dl, P < 0.0002, respectively) and asymptomatic infected subjects (3.4 +/- 2.1 mg/liter, P = 0.001, and 436 +/- 216 mg/dl, P < 0.0001, respectively) compared with the levels in healthy subjects (2.2 +/- 0.7 mg/liter and 204 +/- 113 mg/dl, respectively). Nonstatistically significant differences (P > 0.05) for concentrations of p24 antigen between asymptomatic infected patients (29 +/- 13 pg/ml) and AIDS patients (40 +/- 23 pg/ml) were observed. Total lymphocyte counts of 1,750 cells/microliters or less, CD4 counts of 200 cells/microliters or less, beta 2-microglobulin concentrations in serum of 4 mg/liter or higher, concentrations of IgA in serum of 450 mg/dl or higher, and the presence in serum of p24 antigen were correlated with elevated risks for developing AIDS. Monitoring both total lymphocytes and beta 2-microglobulin identified 91% of the AIDS patients; these assays may allow reductions in the annual number of CD4(+)-cell evaluations and the costs associated with monitoring both total lymphocytes and beta 2-microglobulin identified 91% of the AIDS patients; these assays may allow reductions in the annual number of CD4(+)-cell evaluations and the costs associated with monitoring the immune status of HIV-positive patients.

Cell cycle-specific behavior of erythropoietin.

The murine erythropoietin-dependent erythroleukemia cell line, HCD-57, was employed to study the cell cycle-specific behavior of erythropoietin. Cell cycle duration for HCD-57 cells was approximately 12 hours and was uninfluenced by erythropoietin. Populations of HCD-57 cells synchronized in G1 by centrifugal elutriation were able to pass through one complete cell cycle in the absence of erythropoietin but, thereafter, arrested in G1 as identified by propidium iodide staining and flow cytometry. Analysis of cell cycle behavior using the metachromic dye acridine orange, however, revealed that HCD-57 cells pass through a G0 cell cycle phase and, like serum-deprived 3T3 cells, actually arrest in G0 when deprived of erythropoietin. Expression of the cell cycle regulatory protein p34cdc2 was invariant throughout the cell cycle in HCD-57 cells. p34cdc2 was constitutively phosphorylated in G0 cells, and this effect was not modified by erythropoietin. Erythropoietin receptor distribution was log normal in HCD-57 cells in each phase of the cell cycle. The affinity of these surface receptors for erythropoietin was essentially invariant throughout the cell cycle, but receptor expression was upregulated in G2M cells as compared with cells in G1 or S phase. Taken together, these data indicate that erythropoietin has an important role in the G0-G1 to S phase transition but, based on receptor expression, is involved in other phases of the cell cycle as well.

Acute renal failure associated with the retinoic acid syndrome in acute promyelocytic leukemia.

All-trans-retinoic acid is an effective agent to induce remission in patients with acute promyelocytic leukemia (APL). Unlike conventional chemotherapy, this drug exerts its effect by inducing differentiation of immature leukemic cells. A distinctive clinical syndrome characterized by fever, dyspnea, effusions, weight gain, and organ failure (the "retinoic acid syndrome") can occur during treatment with this drug. Postmortem studies have shown extensive organ infiltration by leukemic cells, and the early administration of corticosteroids can result in prompt resolution of symptoms. We describe a patient with APL in whom acute renal failure developed during treatment with all-trans-retinoic acid. Transient renal enlargement during a period of leukocytosis and a beneficial response to treatment with dexamethasone suggest that renal failure in this patient was probably related to the retinoic acid syndrome.

Identification of arteriovenous anastomoses by duplex ultrasound. Implications for the treatment of varicose veins.

BACKGROUND: It has been suggested that arteriovenous anastomoses (AVA) may contribute to the etiology of varicose vein disease. Duplex ultrasound has recently assumed a major role in the diagnosis of venous disease. This noninvasive method can serve as a research tool to better elucidate the role of AVA, and as a guide to the treatment of varicose veins. OBJECTIVE: To determine the incidence and location of AVA identifiable by duplex ultrasound in a population with clinically apparent varicose veins due to underlying saphenous vein reflux. METHODS: The presence and location of AVA detected by duplex ultrasound were noted in 510 patients with varicose veins due to Doppler-positive saphenous vein reflux from three private practices. RESULTS: Twenty-six AVA were found in 19 patients (incidence 3.7%), mostly in the distal half of the long saphenous system. AVA were represented equally on both right and left sides, and regardless of previous vein stripping. Three AVA were found at the base of venous ulcers. AVA were more easily detected using higher resolution ultrasound. CONCLUSION: AVA occurring in association with saphenous vein disease and identified using duplex ultrasound are usually found below the knee in the long saphenous system, and sometimes at the base of venous ulcers. Knowledge of their presence and location may help to avert complications of sclerotherapy, and guide the approach to treatment.

[Gene frequency and haplotypes of the HLA system in the Panamanian population]. / Frecuencia de genes y haplotipos del sistema HLA en la poblacion Panameña.

The authors determined the frequency of genes and haplotypes of the HLA system in 965 panamanian men and women not related to each other, between 6 and 65 years of age. The HLA-A locus genes with the highest frequency (f) were A2, with f 0.1763; A24, f 0.1584; A30, f 0.1340; A23, f 0.1069; A3, f 0.0774. The other 20 genes each had less than 0.07. The genes with the highest frequency for locus HLA-B were B35, f 0.1946; B44, f 0.0904; B7, f 0.0774; B60 and B61, f 0.0582. For locus HLA-C, the most frequent genes were Cw3 with f 0.1549 and Cw4, f 0.1444. For locus HLA-DR, the most frequent genes were DR2 with f 0.1283; DR3, f 0.0620; DR7, f 0.0409. The most frequent haplotypes in the panamanian population were A2-B35 with f 0.0382; A3-B35, f 0.0191; A24-35, f 0.0287; A24-B61, f 0.0239; A29-B44, f 0.0287; A30-B42, f 0.0239; A23-B44, f 0.0191; A1-B8, f 0.0143. The authors conclude that the panamanian population exhibits a high degree of polymorphism for loci HLA-A, B and C, while for locu HLA-DR the frequency is the median when compared with that in caucasian, negro and oriental groups; and that, according to locus, predominant genes originating from these groups and found, corroborating the multiracial origen of the panamanian population.