Predictors of mortality in critically ill patients with COVID-19 and diabetes.

The COVID-19 pandemic has challenged the entire world, and patients with diabetes mellitus (DM) have been particularly affected. We aimed to evaluate predictors of mortality during the first 30 days of hospitalization in critically ill patients with COVID-19 and comorbid DM. This prospective study included 110 critically ill patients admitted with COVID-19 infection. Thirty-two (29%) patients had a previous diagnosis of DM. Clinical variables, laboratory tests, and vascular biomarkers, such as VCAM-1, syndecan-1, ICAM-1, angiopoietin-1, and angiopoeitin-2, were evaluated after intensive care unit (ICU) admission. A comparison was made between patients with and without DM. No difference in mortality was observed between the groups (48.7 vs 46.9%, P=0.861). In the multivariate Cox regression analysis, VCAM-1 levels at ICU admission (HR: 1 [1-1.001], P<0.006) were associated with death in patients with DM. Among patients with DM, advanced age (HR 1.063 [1.031-1.096], P<0.001), increased Ang-2/Ang-1 ratio (HR: 4.515 [1.803-11.308] P=0.001), and need for dialysis (HR: 3.489 [1.409-8.642], P=0.007) were independent predictors of death. Higher levels of VCAM-1 in patients with DM was better at predicting death of patients with severe COVID-19 and comorbid DM, and their cut-off values were useful for stratifying patients with a worse prognosis. Vascular biomarkers VCAM-1 and Ang-2/Ang-1 ratio were predictors of death in patients with severe COVID-19 and comorbid DM and those without DM. Additionally, kidney injury was associated with an increased risk of death.

Predictors of mortality in critically ill patients with COVID-19 and diabetes

The COVID-19 pandemic has challenged the entire world, and patients with diabetes mellitus (DM) have been particularly affected. We aimed to evaluate predictors of mortality during the first 30 days of hospitalization in critically ill patients with COVID-19 and comorbid DM. This prospective study included 110 critically ill patients admitted with COVID-19 infection. Thirty-two (29%) patients had a previous diagnosis of DM. Clinical variables, laboratory tests, and vascular biomarkers, such as VCAM-1, syndecan-1, ICAM-1, angiopoietin-1, and angiopoeitin-2, were evaluated after intensive care unit (ICU) admission. A comparison was made between patients with and without DM. No difference in mortality was observed between the groups (48.7 vs 46.9%, P=0.861). In the multivariate Cox regression analysis, VCAM-1 levels at ICU admission (HR: 1 [1-1.001], P<0.006) were associated with death in patients with DM. Among patients with DM, advanced age (HR 1.063 [1.031-1.096], P<0.001), increased Ang-2/Ang-1 ratio (HR: 4.515 [1.803-11.308] P=0.001), and need for dialysis (HR: 3.489 [1.409-8.642], P=0.007) were independent predictors of death. Higher levels of VCAM-1 in patients with DM was better at predicting death of patients with severe COVID-19 and comorbid DM, and their cut-off values were useful for stratifying patients with a worse prognosis. Vascular biomarkers VCAM-1 and Ang-2/Ang-1 ratio were predictors of death in patients with severe COVID-19 and comorbid DM and those without DM. Additionally, kidney injury was associated with an increased risk of death.

Nasal CPAP complications in very low birth weight preterm infants.

BACKGROUND: Nasal trauma due to nasal CPAP (nCPAP) use is a commonly reported complication in infants under 1500 g of birth weight and 32 weeks of gestation. With the rise of nCPAP as the gold standard for non-invasive respiratory support, preventive measures should be considered. OBJECTIVE: To assess the prevalence and risk factors of nasal injury in very low birth weight (VLBW) preterm infants with nCPAP. METHODS: We retrospectively analyzed neonates hospitalized between 2012 and 2017, with less than 1500 g and 32 weeks of gestational age who received more than 12 hours of nCPAP. Demographic, antenatal and clinical data, along with information regarding respiratory support and nCPAP complications, were collected. We used Fischer's classification to grade nasal trauma. RESULTS: A total of 135 infants were evaluated. Mean gestational age was 28 weeks (SD 2) and mean birth weight 1072 g (SD 239). Nasal trauma was reported in 65% of patients and it was of stage I, II and III in 49%, 16% and 1% of patients, respectively. The multivariate logistic regression revealed that the risk of trauma was greater in neonates with a longer duration of nCPAP ventilation (OR = 1.098, 95% CI: 1.055-1.142; p < 0.001) and in patients submitted to oxygen therapy (OR = 3.174, 95% CI: 1.014-9.929, p = 0.004). The median of days after nCPAP administration until the onset of an identifiable lesion was 4. CONCLUSION: Nasal trauma is a frequent complication in VLBW preterm infants using nCPAP for long periods. Preventive measures in patients who are at greater risk of skin breakdown are of major clinical importance for a better outcome.

Sarcopenia and outcomes in ventral hernia repair: a preliminary review.

PURPOSE: Sarcopenia, or loss of muscle mass, is associated with increased morbidity and mortality in oncologic resections and several other major surgeries. Complex ventral hernia repairs (VHRs) and abdominal wall reconstruction are often performed in patients at high risk for morbidity and recurrence, though limited data exist on outcomes related to sarcopenia. We aimed to determine if sarcopenia is associated with worse outcomes in patients undergoing VHR. METHODS: We reviewed patients undergoing VHRs from 2014 to 2015. Preoperative CT images were analyzed for cross-sectional muscle mass. Patients with and without sarcopenia underwent statistical analysis to evaluate differences in perioperative morbidity and hernia recurrence. Muscle indices were analyzed independently for outcomes. RESULTS: 135 patients underwent VHR with/without fistula takedown, staged repairs or other concomitant procedures. 27% had sarcopenia (age 34-84, BMI 27-33, 62% male). Postoperative complications occurred in 43% of sarcopenic patients and 47% of non-sarcopenic patients (p = 0.70). Surgical site infections (SSI) were seen in 16% of sarcopenic patients compared to 29% without sarcopenia (p = 0.14). There was no difference in hernia recurrence between groups (p = 0.90). However, after adjusting for diabetes and BMI, a 10 cm2/m2 decrease in muscle index had 1.44 OR of postoperative complications (p < 0.05). CONCLUSIONS: Though prevalent in our population, sarcopenia was not associated with an increase in postoperative complications, surgical site occurences/infections,  or hernia recurrence when previously published oncologic sarcopenia cutoffs were utilized. Previously established sarcopenia outcomes in malignancy may be attributable to an altered metabolic state that is not present in hernia repair patients. Larger-scale studies are recommended to establish new sarcopenia cutoffs for VHRs.

Formation of alkali-soluble fluoride on the surface of human dental enamel after treatment with fluoridated gels: influence of the pH variation and of the treatment time.

The aim of this study was to quantify, in vitro, the formation of CaF2 after the application of three fluoridated gels: one neutral, one acidulated and another highly acidulated, on a bovine enamel dental surface treated with a Dijkman's demineralizing solution (1990). 145 sections were utilized, obtained from 145 sound teeth and divided into seven groups: C (enamel without treatment); FN1 (enamel demineralized and treated with neutral gel for 1 minute); FN4 (enamel demineralized and treated with neutral gel for 4 minutes); FFA1 (enamel demineralized and treated with acidulated gel for 1 minute); FFA4 (enamel demineralized and treated with acidulated gel for 4 minutes); FAA1 (enamel demineralized and treated with highly acidulated gel for 1 minute) and FAA4 (enamel demineralized and treated with highly acidulated gel for 4 minutes). The formation of CaF2 was analyzed by SEM and chemically by Caslavska's method (1975). The average and standard deviations from the groups studied were respectively: C-0.63; 0.38; FN1-23.06; 16.52; FFA1-54.11; 49.00; FAA1-43.87; 32.66; FN4-34.92; 23.00; FFA4-67.91; 42.36; FAA4-56.03; 38.96. (Mann-Whitney non-parametric test). The time of application did not interfere in the CaF2 formation from the acidulated and highly-acidulated gels. A minor concentration of fluoride and amount of pH from highly-acidulated gel did not affect the higher formation from the CaF2 in relation to the acidulated gel in both cases when the application was evaluated.

Metabolic fate of glutamine in lymphocytes, macrophages and neutrophils.

Eric Newsholme's laboratory was the first to show glutamine utilization by lymphocytes and macrophages. Recently, we have found that neutrophils also utilize glutamine. This amino acid has been shown to play a role in lymphocyte proliferation, cytokine production by lymphocytes and macrophages and phagocytosis and superoxide production by macrophages and neutrophils. Knowledge of the metabolic fate of glutamine in these cells is important for the understanding of the role and function of this amino acid in the maintenance of the proliferative, phagocytic and secretory capacities of these cells. Glutamine and glucose are poorly oxidized by these cells and might produce important precursors for DNA, RNA, protein and lipid synthesis. The high rate of glutamine utilization and its importance in such cells have raised the question as to the source of this glutamine, which, according to current evidence, appears to be muscle.

Echoplanar chemical shift imaging.

A novel method of chemical shift imaging utilizing echoplanar imaging (EPI) has been developed for the purpose of improving the spatial resolution of metabolite images for the specific goal of high spatial resolution mapping of neuronal content. An EPI sequence was modified to allow temporal offsets of the 180 degree refocusing pulse that encode the chemical shift information into the phase of the signal. Implementation of this method on 1.5 and 3 T human imagers has resulted in images of N-acetyl aspartate in humans with spatial resolution of 360 microl and signal-to-noise ratio approximately 7:1 in less than 13 min.

Metabolic fate of glutamine in lymphocytes, macrophages and neutrophils

Eric Newsholme's laboratory was the first to show glutamine utilization by lymphocytes and macrophages. Recently, we have found that neutrophils also utilize glutamine. This amino acid has been shown to play a role in lymphocyte proliferation, cytokine production by lymphocytes and macrophages and phagocytosis and superoxide production by macrophages and neutrophils. Knowledge of the metabolic fate of glutamine in these cells is important for the understanding of the role and function of this amino acid in the maintenance of the proliferative, phagocytic and secretory capacities of these cells. Glutamine and glucose are poorly oxidized by these cells and might produce important precursors for DNA, RNA, protein and lipid synthesis. The high rate of glutamine utilization and its importance in such cells have raised the question as to the source of this glutamine, which, according to current evidence, appears to be muscle

Imaging subcortical auditory activity in humans.

There is a lack of physiological data pertaining to how listening humans process auditory information. Functional magnetic resonance imaging (fMRI) has provided some data for the auditory cortex in awake humans, but there is still a paucity of comparable data for subcortical auditory areas where the early stages of processing take place, as amply demonstrated by single-unit studies in animals. It is unclear why fMRI has been unsuccessful in imaging auditory brain-stem activity, but one problem may be cardiac-related, pulsatile brain-stem motion. To examine this, a method eliminating such motion (using cardiac gating) was applied to map sound-related activity in the auditory cortices and inferior colliculi in the brain stem. Activation in both the colliculi and cortex became more discernible when gating was used. In contrast with the cortex, the improvement in the colliculi resulted from a reduction in signal variability, rather than from an increase in percent signal change. This reduction is consistent with the hypothesis that motion or pulsatile flow is a major factor in brain-stem imaging. The way now seems clear to studying activity throughout the human auditory pathway in listening humans.

Increased cerebral blood volume in HIV-positive patients detected by functional MRI.

OBJECTIVE: To study changes in cerebral hemodynamics related to HIV infection. BACKGROUND: Cerebral injury is a well-known manifestation of HIV infection. Physiologic changes in the HIV brain may precede structural changes and may be detected by functional MRI (fMRI). METHODS: Dynamic contrast fMRI was used to measure the cerebral blood volume (CBV) in 13 patients infected with HIV and in 7 healthy control subjects. RESULTS: Significant increases in dynamic CBV were found in the deep (p < 0.001) and cortical gray matter (p < 0.05) of HIV-positive (HIV+) patients. Patients with definite cognitive impairment showed significantly greater increases in CBV in the deep gray matter (DGM) compared with those without impairment. In one patient with rapidly progressive cognitive impairment, these abnormalities reversed and paralleled clinical improvement after initiation of zidovudine monotherapy. CONCLUSIONS: This study supports the hypothesis that HIV infection is associated with significant cerebral hemodynamic changes, particularly in the DGM, that may contribute to cognitive dysfunction in AIDS. Functional MRI may be useful for early detection of cerebral injury and for the assessment of novel therapies.

Treatment of malnutrition in Brazil: simple solutions to common problems.

At the largest rehabilitation centre in Ceará, Brazil, the World Health Organization (WHO) guidelines for improved dietary management of severe malnutrition were implemented. Rates of weight gain increased fourfold, daily food costs were reduced, and staff time was saved. Implementation was achieved within 1 week, including training. Other centres are encouraged to adopt similar measures.

The effect of N-3 PUFA rich diet upon macrophage and lymphocyte metabolism and function.

A large body of evidence from experimental studies has documented that n-3 fatty acids can modify a variety of cell functions and disease states. As lymphocytes and macrophages are important cells for the development of the inflammatory and non-inflammatory immune response and are known to utilize high rates of glucose and glutamine, we have evaluated the effect of n-3 PUFA rich diet on the metabolisation of glucose and glutamine these cells, as well as the effect of one such diet upon the proliferative response of lymphocytes and the phagocytic capacity and hydrogen peroxide production by macrophages. The diet provoked an increase in the flux of glucose through the Krebs cycle in macrophages as well as a reduction in G6PDh and glutaminase activity in these cells. Lymphocytes from n-3 PUFA rich diet-fed rats showed a reduction in glucose and glutamine decarboxylation. Taken together the data show that, at least in part, the functional changes observed in macrophages and lymphocytes from n-3 PUFA-rich diet fed rats are related to the effect of this diet upon glucose and glutamine metabolism, leading to immunosuppression.

The hippocampal formation participates in novel picture encoding: evidence from functional magnetic resonance imaging.

Considerable evidence exists to support the hypothesis that the hippocampus and related medial temporal lobe structures are crucial for the encoding and storage of information in long-term memory. Few human imaging studies, however, have successfully shown signal intensity changes in these areas during encoding or retrieval. Using functional magnetic resonance imaging (fMRI), we studied normal human subjects while they performed a novel picture encoding task. High-speed echo-planar imaging techniques evaluated fMRI signal changes throughout the brain. During the encoding of novel pictures, statistically significant increases in fMRI signal were observed bilaterally in the posterior hippocampal formation and parahippocampal gyrus and in the lingual and fusiform gyri. To our knowledge, this experiment is the first fMRI study to show robust signal changes in the human hippocampal region. It also provides evidence that the encoding of novel, complex pictures depends upon an interaction between ventral cortical regions, specialized for object vision, and the hippocampal formation and parahippocampal gyrus, specialized for long-term memory.

Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: A proton magnetic resonance spectroscopic study.

The CNS is frequently involved in human immunodeficiency virus (HIV) infection. In recent studies using proton magnetic resonance spectroscopy, investigators found a significant reduction in N-acetyl aspartate, a metabolic marker of neurons, in late stages of dementia. To further understand the relationship between proton magnetic resonance spectroscopy changes and clinical disease and dementia, we compared 20 HIV-infected patients presenting at varying stages of acquired immunodeficiency syndrome (AIDS) dementia complex and infection to 10 age-matched controls. We found a significant reduction in N-acetyl aspartate/creatine only in patients who had advanced dementia and CD4 counts less that 200/microliter. By contrast, a significant elevation in compounds containing choline was present in patients in the early stages of HIV infection of who had CD4 counts greater than 200/microliter, in patients with normal MRI scans, and in all AIDS dementia complex groups, including subjects with no or minimal cognitive impairment. An elevated choline level also occurred in later stages of HIV infection (CD4 < 200/microliter). Our results suggest that an increase in choline occurs before N-acetyl aspartate decrements, MRI abnormalities, and the onset of dementia, and may therefore provide a useful marker for early detection of brain injury associated with HIV infection.

Quantitative in vivo 31P magnetic resonance spectroscopy of Alzheimer disease.

The purpose of this study was to determine whether, in Alzheimer disease (AD) patients, abnormalities in energy charge or phospholipid metabolism could be detected during life with quantitative phosphorus magnetic resonance spectroscopy (31P MRS). We performed in vivo 31P MRS in 16 patients with a clinical diagnosis of probable AD with mild to moderate dementia severity (mean Blessed Dementia Score = 17.5, range = 7-37) and in 8 healthy, nondemented, age-matched, control subjects. MR studies were performed on a commercial 1.5 T MR imager using a volume head coil. We acquired brain spectra by sampling a 6-cm-thick axial slice through the cerebrum (a region that includes approximately 900 ml of brain tissue); we measured beta-nucleoside triphosphate (beta-NTP), phosphocreatine (PCr), phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Pi) concentrations, then calculated ratios of these resonances. The beta-NTP, PCr, and Pi resonances in AD and control subjects were not significantly different. These data indicate that brain energy stores are not depleted in AD. No significant differences were detected in the absolute measurements of PME and PDE between the AD and control groups. However, among the calculated ratios, an increase in the PME/PDE ratio of approximately 50%, mostly due to a decrease in the PDE signal, was statistically significant (AD PME/PDE mean = 0.35, range 0.13-0.71; normal PME/PDE mean = 0.22, range 0.16-0.34). We speculate that the difference in PDE reflects changes in the biophysical state of membrane phospholipids in AD.

Quantitative in vivo 1H nuclear magnetic resonance spectroscopic imaging of neuronal loss in rat brain.

The aim of this research was to determine whether in vivo nuclear magnetic resonance spectroscopic measurement of N-acetyl aspartate, a neuron specific brain marker, provides a quantitative index of neuronal loss. Five rats were injected unilaterally in the corpus striatum with kainic acid, an analogue of glutamate that causes excitotoxic degeneration of intrinsic neurons, and were subjected to nuclear magnetic resonance imaging and spectroscopic imaging. Measurements of N-acetyl aspartate were determined in vivo and compared to post mortem nuclear magnetic resonance spectroscopic measures of N-acetyl aspartate and choline acetyl transferase and glutamate decarboxylase activities, biochemical markers for striatal intrinsic neuronal integrity. Mean per cent neuronal survival of hemispheres with lesion versus the contralateral hemispheres measured 72 for glutamate decarboxylase and 71 for N-acetyl aspartate (in vivo), 74 for N-acetyl aspartate (in vitro), and 62 for choline acetyl transferase, respectively. Our studies in rats have shown that estimates of neuronal loss through nuclear magnetic resonance spectroscopic measurements of N-acetyl aspartate are equivalent to traditional neuronal enzyme activity assays. The results unequivocally demonstrate that N-acetyl aspartate is a valid and sensitive neuronal marker with the capability of providing accurate assessments of neuronal loss in vivo.

Functional MR in the evaluation of dementia: correlation of abnormal dynamic cerebral blood volume measurements with changes in cerebral metabolism on positron emission tomography with fludeoxyglucose F 18.

PURPOSE: To determine whether magnetic susceptibility functional MR imaging of cerebral blood volumes provides information similar to fludeoxyglucose F 18 positron emission tomography (PET) brain images in patients undergoing evaluation for dementia. METHODS: Ten subjects were studied with both PET and functional MR. Clinical diagnoses included probable Alzheimer disease (n = 5), possible Alzheimer disease (n = 1), Pick disease (n = 2), and primary progressive aphasia (n = 2). The studies were quantitatively evaluated by coregistration of PET and functional MR images followed by regression analyses of corresponding regions of interest. Qualitatively, each brain was categorized into eight regions, and each was classified as normal or abnormal by visual inspection. RESULTS: Correlation coefficients between registered functional MR and PET images were excellent (mean, r = 0.58) in most of the cerebrum. Significant correlations were observed in 72 of 74 brain sections. Qualitatively, 16 brain regions were judged to be abnormal by both MR imaging and PET; 46 regions were normal by both; 10 regions were abnormal by PET only; and 8 regions were abnormal only by functional MR. The concordance between functional MR and PET was 78%, which was highly significant. CONCLUSION: Cerebral blood volumes images derived from magnetic susceptibility (functional MR) provide information similar to fludeoxyglucose F 18 PET images in demented patients undergoing evaluation for dementia.

Variability of brain lithium levels during maintenance treatment: a magnetic resonance spectroscopy study.

In vivo magnetic resonance spectroscopy (MRS) was used to determine the relationship between serum and brain lithium levels in bipolar patients (n=25). Over the broad range of serum lithium levels observed, the correlation (r=.68) with brain lithium levels was high. This correlation was much weaker (r=.39) when limited to only those patients with serum lithium levels in the range of 0.6-1.0 mmol/l. This variability may account for failure of lithium prophylaxis in some patients who have serum lithium levels in the therapeutic range.

Composition of fatty acids in the liver and lymphoid organs of rats fed fatty acid-rich diets.

The composition of the fatty acids in the thymus, spleen and mesenteric lymph nodes was determined in rats fed polyunsaturated (UFC) or saturated (SFC) fatty acid-rich chow during 6 weeks or 14 months. The results indicated that the lipid composition of fatty acids in these tissues was modified by the type of fat given in the diets. Interestingly, the liver did not show any dietary induced change in the composition of fatty acids. The unsaturation index was raised in the lymphoid organs by UFC either after 6 weeks or 14 months. The ageing process itself increased the degree of unsaturation of fatty acids only in the spleen of the 3 groups. A high degree of unsaturation of fatty acids in the tissues may favour the occurrence of lipid peroxidation. It was noteworthy that a linoleic acid-rich diet (UFC) did not change the content of arachidonic acid in the tissues and so would therefore be unlikely to affect eicosanoid synthesis. As shown by previous studies, these fat-rich diets caused marked changes in the key enzyme activities of glucose and glutamine metabolism in the lymphoid organs, by as yet unknown mechanisms. The results reported here suggest that the effect of fat-rich diets on intermediary metabolism does not occur through eicosanoid synthesis and may be a consequence of the lipid peroxidative process or even alterations in the transcription of the enzymes of glycolysis and glutaminolysis.

Antioxidant enzyme activities in the lymphoid organs and muscles of rats fed fatty acids-rich diets subjected to prolonged physical exercise-training.

Rats weighing 45-50 g were fed 3 diets for 8 wk: a balanced control diet (CD) consisting of 4% fat (polyunsaturated/saturated fatty acids [P/S] ratio 2.9/1) and two fat-rich diets: polyunsaturated (UD)--P/S 7.6/1 and saturated (SD) P/S 0.3/1. After 8 wk feeding on the respective diets, rats were subjected to swimming for 90 min at 30 degrees C daily, 5 d/wk for 8 wk. At the end of this period, the rats were killed and the lymphoid organs (LO--thymus, spleen, and mesenteric lymph nodes) and muscles (soleus and gastrocnemius) removed for the measurement of TBARs (Thiobarbituric Acid Reactant Substances) content and of the activities of antioxidant enzymes (CuZn- and Mn-Superoxide dismutase--SOD--, catalase, and glutathione peroxidase). To evaluate the changes in the sites of generation of reducing equivalents involved in the formation of free radicals, the activities of citrate synthase and glucose-6-phosphate dehydrogenase were measured. The exercise-training clearly modified the enzyme activities and TBARs content of the lymphoid organs and skeletal muscles, but this effect was dependent upon the diet given to the rats. However, fatty acid rich diets had presented a more pronounced effect on the studied aspects than did physical activity. Although one could expect a summatory effect of polyunsaturated fatty acid-rich diet and exercise-training, swimming increased the activities of CuZn- and Mn-SOD in almost all tissues from the elevated level promoted by fat-rich diets.