Comparison of Changes in PPV Using a Tidal Volume Challenge with a Passive Leg Raising Test to Predict Fluid Responsiveness in Patients Ventilated Using Low Tidal Volume.

BACKGROUND: Tidal volume challenge pulse pressure variation (TVC-PPV) is considered one of the recent reliable dynamic indices of fluid responsiveness (FR); also, passive leg raising (PLR)-induced changes in cardiac output (CO) detected by echocardiography are considered a reliable reversible self-fluid challenge test; many patients share eligibility for both tests. OBJECTIVES: The study aimed to compare the sensitivity and specificity of both tests for the prediction of FR in mechanically ventilated patients with hemodynamic instability. METHODS: We studied 46 patients. Hemodynamic parameters including PPV and CO (detected by velocity time integral (VTI) using echocardiography) recorded at tidal volume (VT) of 6 mL/kg/ideal body weight (IBW) in semi-recumbent position then recorded again after one-minute increase in TV from 6 to 8 mL/kg/IBW then recorded with PLR at TV of 6 mL/kg/IBW and finally with actual volume expansion in semi-recumbent position by 4 ml/kg bolus of crystalloid solution to define actual responders with increase of cardiac output of 15% or more. RESULTS: Sixteen patients were responders, and thirty patients were nonresponders; responders had significant increase in PPV with TVC 6 to 8 ml/kg/IBW with best cutoff value of 3.5 with a sensitivity of 93.8% and a specificity of 93.9%. PLR test-induced changes in CO had a sensitivity of 93.9% and a specificity of 86.7% with statistically best cutoff value of 6.5% increase in CO, but sensitivity was 75% at cutoff value of 10% increase in CO. Other parameters like PPV, PPV changes with PLR test, and PPV changes with fluid expansion were less sensitive indicators. CONCLUSION: FR in patients with hemodynamic instability and mechanically ventilated with low tidal volume strategy can be efficiently predicted when PPV increases more than 3.5 with tidal volume challenge and when PLR induces 6.5% increase in CO monitored through VTI method by Doppler echocardiography, and both tests are equally reliable. HOW TO CITE THIS ARTICLE: Elsayed AI, Selim KAW, Zaghla HE, Mowafy HE, Fakher MA. Comparison of Changes in PPV Using a Tidal Volume Challenge with a Passive Leg Raising Test to Predict Fluid Responsiveness in Patients Ventilated Using Low Tidal Volume. Indian J Crit Care Med 2021;25(6):685-690.

Evaluation of the effects of altitude on biological signatures of inflammation and anxiety- and depressive-like behavioral responses.

Over sixteen million people suffer from a depressive episode annually in the United States, with females affected at twice the rate of males. Little is known about the effects of exposure to high altitude on the risk of development of major depressive disorder, despite reports of higher suicide rates at higher altitudes. We hypothesize that exposure to hypobaric hypoxia at high altitude increases endophenotypes of self-directed suicidal violence, including biological signatures of chronic inflammation and vulnerability to anxiety-like and depressive-like behavioral responses in a sex-specific manner. Biological signatures of inflammation, including granulocyte:lymphocyte ratios, monocyte cell counts, and monocyte:lymphocyte ratios were assessed using complete blood count data, anhedonia, and anxiety- and depressive-like behavioral responses were evaluated. We assessed biological signatures of inflammation and behavioral responses in the open-field test, sucrose preference test, and modified Porsolt forced swim test in young adult male and female Long-Evans and Sprague Dawley rats. All tests were conducted near sea level (374 ft [114 m] elevation) and at moderate-high altitude (5430 ft [1655 m] elevation) during acclimation periods of one, two, three, four, and five weeks following shipment from a sea level animal breeding facility (N = 320, n = 8 per group). Exposure to moderate-high altitude induced a biological signature of increased inflammation, as evidenced by main effects of altitude for: 1) increased granulocyte:lymphocyte ratio; 2) increased count and relative abundance of circulating monocytes; and 3) increased monocyte:lymphocyte ratios. Exposure to moderate-high altitude also increased anhedonia as assessed in the sucrose preference test in both male and female rats, when data were collapsed across strain and time. Among male and female Long Evans rats, exposure to moderate-high altitude increased immobility in the forced swim test, without changing anxiety-like behaviors in the open-field test. Finally, granulocyte:lymphocyte ratios were correlated with anhedonia in the sucrose preference test. These data are consistent with the hypothesis that hypobaric hypoxia at moderate-high altitude induces persistent endophenotypes of self-directed suicidal violence including biological signatures of inflammation, anhedonia, and depressive-like behavioral responses.

Comparing the effects of two different strains of mycobacteria, Mycobacterium vaccae NCTC 11659 and M. vaccae ATCC 15483, on stress-resilient behaviors and lipid-immune signaling in rats.

Stress-related disorders, such as posttraumatic stress disorder (PTSD), are highly prevalent and often difficult to treat. In rodents, stress-related, anxiety-like defensive behavioral responses may be characterized by social avoidance, exacerbated inflammation, and altered metabolic states. We have previously shown that, in rodents, subcutaneous injections of a heat-killed preparation of the soil-derived bacterium Mycobacterium vaccae NCTC 11659 promotes stress resilience effects that are associated with immunoregulatory signaling in the periphery and the brain. In the current study, we sought to determine whether treatment with a heat-killed preparation of the closely related M. vaccae type strain, M. vaccae ATCC 15483, would also promote stress-resilience in adult male rats, likely due to biologically similar characteristics of the two strains. Here we show that immunization with either M. vaccae NCTC 11659 or M. vaccae ATCC 15483 prevents stress-induced increases in hippocampal interleukin 6 mRNA expression, consistent with previous studies showing that M. vaccae NCTC 11659 prevents stress-induced increases in peripheral IL-6 secretion, and prevents exaggeration of anxiety-like defensive behavioral responses assessed 24 h after exposure to inescapable tail shock stress (IS) in adult male rats. Analysis of mRNA expression, protein abundance, and flow cytometry data demonstrate overlapping but also unique effects of treatment with the two M. vaccae strains on immunological and metabolic signaling in the host. These data support the hypothesis that treatment with different M. vaccae strains may immunize the host against stress-induced dysregulation of physiology and behavior.

Alzheimer's Disease: Protective Effects of Mycobacterium vaccae, a Soil-Derived Mycobacterium with Anti-Inflammatory and Anti-Tubercular Properties, on the Proteomic Profiles of Plasma and Cerebrospinal Fluid in Rats.

BACKGROUND: Alzheimer's disease (AD) is an inflammatory neurodegenerative disease that may be associated with prior bacterial infections. Microbial "old friends" can suppress exaggerated inflammation in response to disease-causing infections or increase clearance of pathogens such as Mycobacterium tuberculosis, which causes tuberculosis (TB). One such "old friend" is Mycobacterium vaccae NCTC 11659, a soil-derived bacterium that has been proposed either as a vaccine for prevention of TB, or as immunotherapy for the treatment of TB when used alongside first line anti-TB drug treatment. OBJECTIVE: The goal of this study was to use a hypothesis generating approach to explore the effects of M. vaccae on physiological changes in the plasma and cerebrospinal fluid (CSF). METHODS: Liquid chromatography-tandem mass spectrometry-based proteomics were performed in plasma and CSF of adult male rats after immunization with a heat-killed preparation of M. vaccae NCTC 11659 or borate-buffered saline vehicle. Gene enrichment analysis and analysis of protein-protein interactions were performed to integrate physiological network changes in plasma and CSF. We used RT-qPCR to assess immune and metabolic gene expression changes in the hippocampus. RESULTS: In both plasma and CSF, immunization with M. vaccae increased proteins associated with immune activation and downregulated proteins corresponding to lipid (including phospholipid and cholesterol) metabolism. Immunization with M. vaccae also increased hippocampal expression of interleukin-4 (IL-4) mRNA, implicating anti-inflammatory effects in the central nervous system. CONCLUSION: M. vaccae alters host immune activity and lipid metabolism. These data are consistent with the hypothesis that microbe-host interactions may protect against possible infection-induced, inflammation-related cognitive impairments.

Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a "Two Hit" Stressor Model.

Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M. vaccae), a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, is a potentially useful countermeasure against negative outcomes to stressors. Here we used male C57BL/6NCrl mice to determine if repeated immunization with M. vaccae is an effective countermeasure in a "two hit" stress exposure model of chronic disruption of rhythms (CDR) followed by acute social defeat (SD). On day -28, mice received implants of biotelemetric recording devices to monitor 24-h rhythms of locomotor activity. Mice were subsequently treated with a heat-killed preparation of M. vaccae (0.1 mg, administered subcutaneously on days -21, -14, -7, and 27) or borate-buffered saline vehicle. Mice were then exposed to 8 consecutive weeks of either stable normal 12:12 h light:dark (LD) conditions or CDR, consisting of 12-h reversals of the LD cycle every 7 days (days 0-56). Finally, mice were exposed to either a 10-min SD or a home cage control condition on day 54. All mice were exposed to object location memory testing 24 h following SD. The gut microbiome and metabolome were assessed in fecal samples collected on days -1, 48, and 62 using 16S rRNA gene sequence and LC-MS/MS spectral data, respectively; the plasma metabolome was additionally measured on day 64. Among mice exposed to normal LD conditions, immunization with M. vaccae induced a shift toward a more proactive behavioral coping response to SD as measured by increases in scouting and avoiding an approaching male CD-1 aggressor, and decreases in submissive upright defensive postures. In the object location memory test, exposure to SD increased cognitive function in CDR mice previously immunized with M. vaccae. Immunization with M. vaccae stabilized the gut microbiome, attenuating CDR-induced reductions in alpha diversity and decreasing within-group measures of beta diversity. Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience.

Cephalic de-mucosalized superiorly-based pharyngeal flap: A modified mucosa-preserving technique for velopharyngeal insufficiency.

INTRODUCTION: Superiorly-based pharyngeal flap (PF) is the most frequently employed surgical technique to correct velopharyngeal insufficiency (VPI). Bared posterior pharyngeal wall might prolong the period of convalescence with throat pain and discomfort. Delayed donor site healing problems and subsequent fibrosis with downward migration of the transposed flap might be one a cause of failure and might necessitate revision. AIM OF THE WORK: To present a modified technique of PF aiming at dealing with the problems of donor site defects via immediate self-mucosal covering of the cephalic portion of the bed. METHODS: This case series study was conducted on patients with persistent VPI. All patients underwent the new modified technique of cephalic de-mucosalized pharyngeal flap (CDPF). The basic premise was to harvest a laterally-based mucosal flap from the upper part of the posterior pharyngeal wall. A superiorly-based pharyngeal flap (with a bared cephalic segment and a mucosalized caudal segment) was elevated off the posterior pharyngeal wall and inserted in the soft palate. Then the laterally-based mucosal flap was spread over the superior part of donor site of the posterior pharyngeal wall. RESULTS: 13 VPI patients were included in this study. Their age ranged from 5 to 12 years with a mean of 5.6 ±â€¯1.2. The follow-up period ranged from 8 to 14 months. All flaps and beds were completely healed within 2-3 weeks and no patients showed flap dehiscence, infection or palatal fistula. Postoperative speech assessment showed significant improvement of velopharyngeal function, resonance balance, and reduction in nasal emission. CONCLUSIONS: The modified technique provides an immediate self-mucosa cover to the superior part of the posterior pharyngeal wall, thus it could promote primary healing at the donor site with a short period of convalescence. CDPF separates the two opposing raw surfaces of the flap and the posterior pharyngeal wall. The mucosal flap might guard against downward migration of the flap.