Venous oxygen saturation and lactate gradient from superior vena cava to pulmonary artery in patients with septic shock

Monitoring of central venous oxygen saturation (ScvO2) is considered comparable with mixed venous oxygen saturation (SvO2) in the initial resuscitation phase of septic shock. Our aim was to assess their agreement in septic shock in the intensive care unit setting and the effect of a potential difference in a computed parameter, namely, oxygen consumption (VO2). In addition, we sought for a central venous to pulmonary artery (PA) lactate gradient. We enrolled 37 patients with septic shock who were receiving noradrenaline infusions, and their attending physicians had placed a PA catheter for fluid management. Blood samples were drawn in succession from the superior vena cava, right atrium (RA), right ventricle, and PA. Hemodynamic and treatment parameters were monitored, and data were compared by correlation and Bland-Altman analysis. Mixed venous oxygen saturation was lower than ScvO2 (70.2% +/- 11.4% vs. 78.6% +/- 10.2%; P < 0.001), with a bias of -8.45% and 95% limits of agreement ranging from -20.23% to 3.33%. This difference correlated significantly to the noradrenaline infusion rate and the oxygen consumption and extraction ratio. These lower SvO2 values resulted in computed VO2v higher than the VO2cv (P < 0.001), with a bias of 104.97 mL min(-1) and 95% limits of agreement from -4.12 to 214.07 mL min(-1). Finally, lactate concentration was higher in the superior vena cava and RA than in the PA (2.42 +/- 3.15 and 2.35 +/- 3.16 vs. 2.17 +/- 3.19 mM; P < 0.01 for both comparisons). Thus, our data suggest that ScvO2 and SvO2 are not equivalent in intensive care unit patients with septic shock. Additionally, the substitution of ScvO2 for SvO2 in the calculation of VO2 produces unacceptably large errors. Finally, the decrease in lactate between RA and PA may support the hypothesis that the mixing of RA and coronary sinus blood is at least partially responsible for the difference between ScvO2 and SvO2.     

Sinus fluid penetration of oral clarithromycin and azithromycin in patients with acute rhinosinusitis

BACKGROUND: The aim of this study was to investigate the extracellular concentration and the degree of sinus fluid penetration of newer macrolides, within the first 24-48 hours of treatment in patients with acute bacterial rhinosinusitis (ABRS), choosing clarithromycin and azithromycin as model antibiotics. An open, noninterventional pharmacokinetic study was performed at a tertiary teaching hospital. METHODS: In 36 outpatients with ABRS, sinus fluid aspirates and serum samples were collected 2, 4, 6, 8, and 12 hours or 2, 6, 12, and 24 hours after the administration of three doses of oral clarithromycin, 500 mg, twice daily or two doses of oral azithromycin, 500 mg, once daily, respectively. Drug concentrations were determined in both matrices by high-performance liquid chromatography with fluorometric detection, and the pH was estimated for all sinus fluid samples. RESULTS: The average clarithromycin sinus fluid concentration was found to be significantly higher than the corresponding azithromycin concentration (2.47 mg/L versus 0.65 mg/L), while the extent of the average sinus fluid penetration, expressed by the ratio of drug concentration in tissue versus serum, was similar for both drugs (115 and 120%, respectively). CONCLUSION: In patients with ABRS, clarithromycin and azithromycin present adequate penetration into sinus fluid to eradicate erythromycin-sensitive strains of Streptococcus pneumoniae. Considering their comparative in vitro activity, the sinus fluid pH effect, and their sinus fluid penetration profile, we may conclude that among the erythromycin-resistant S. pneumoniae strains, clarithromycin might be advantageous over azithromycin in eradicating some of the low-level resistant strains.     

Understanding mind–body disciplines: A pilot study of paced breathing and dynamic muscle contraction on autonomic nervous system reactivity

Mind–body disciplines such as yoga, Tai Chi, and Qigong have been demonstrated to activate the parasympathetic nervous system, but it remains unclear how these practices achieve these results, whether by breathing, movement, or some combination. This pilot study establishes a model to examine the individual and combined effects of paced breathing and rhythmic skeletal muscle contraction on the activation of the parasympathetic system during a cognitive stressor. Male participants were randomly assigned to one of four preconditioning groups: (a) paced breathing alone, (b) alternating upper extremity muscle contractions, (c) paced breathing synchronized with alternating contractions, or (d) a neutral control task. Autonomic response was assessed by heart rate variability during a standardized cognitive stressor. The alternating contraction group had 71.7% higher activation of parasympathetic signal over respiration alone (p < .001). Alternating contractions synchronized with breathing demonstrated 150% higher parasympathetic activation than control (p < .0001). Comparing the contraction alone and synchronized groups, the synchronized group demonstrated 45.9% higher parasympathetic response during a cognitive stressor (p < .001). In conclusion, paced breathing synchronized with rhythmic muscle contraction leads to more resilient activation of the parasympathetic response than either alternating contractions or breathing alone, which may help explain the stress reducing benefits of mind–body disciplines.     

Diminishing Significance of HLA Matching in Kidney Transplantation

To determine trends in the significance of HLA matching and other risk factors in kidney transplantation, we analyzed data on graft survival in a consecutive sample of 33 443 transplant recipients who received deceased donor kidneys from December 1994 to December 1998 with a mean follow-up time of 2.2 years. HLA matching and other risk factors (peak panel reactive antibody, donor age, sex and cause of death, cold ischemia time, donor and recipient body size) were examined. Mean likelihood ratios of models, fit with and without each variable of interest, were calculated by generating bootstrapped samples from each single year cohort. Pooled censored and uncensored graft survival rates were 90.6% and 89.9% at 1 year, 85.8% and 84.5% at 2 years, and 80.7% and 78.6% at 3 years. HLA matching declined in significance while other factors retained similar levels of statistical significance over the four yearly cohorts. With evolving clinical practice, including the provision of safer and more potent immunosuppressive therapy, the significance of HLA matching has diminished. Non-immunologic factors continue to impede more marked improvements in long-term graft survival. Recognizing these trends, organ allocation algorithms may need to be revised.     

Phase I/II Trial of External Irradiation plus Medium-Dose Brachytherapy Given Concurrently to Liposomal Doxorubicin and Cisplatin for Advanced Uterine Cervix Carcinoma

BACKGROUND AND PURPOSE: Although the standard of care for patients with locally advanced uterine cervix carcinoma is cisplatin-(CDDP-)based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer. PATIENTS AND METHODS: 24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m2/week was increased in 5-mg/m2 increments to two levels. The standard dose of CDDP was 20-25 mg/m2/week. RESULTS: Concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m2/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6). CONCLUSION: Conclusion: The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m2/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising.     

Low Reported Adherence to the 2019 American Diabetes Association Nutrition Recommendations among Patients with Type 2 Diabetes Mellitus,Indicating the Need for Improved Nutrition Education and Diet Care

Patient adherence to guidelines is important for improved outcomes and prognosis. Nevertheless, many patients with type 2 diabetes mellitus (T2DM) do not comply with the recommendations regarding medication, physical activity, diet or self-care. The present cross-sectional study aimed to assess the level of adherence to the dietary recommendations issued by the American Diabetes Association (ADA) among patients with T2DM in Komotini, Greece. A total of 162 adults with T2DM (64.7 ± 10.6 years old), of which 41.4% were men, were recruited from the Sismanoglio Hospital and participated in the study. The level of adherence to individual recommendations issued by the ADA was assessed using yes/no questions. The overall adherence rate to the guidelines was low (41.2%). According to the multivariable analysis, age and medication therapy were identified as contributors to the compliance rate. No differences were noted in the total compliance rate between patients of different religious denominations (Muslims/Christians). Patients on oral antidiabetic agents (OAA) were more adherent compared with those on insulin therapy. A mere 3.7% of the participants had received nutrition education by a registered dietitian, 9.9% were following an individualized diet plan to improve glycemia, and 3.1% had set specific energy goals to reduce body weight. These findings are indicative of the need for the delivery of improved nutrition education.     

Low FODMAP Diet for Functional Gastrointestinal Symptoms in Quiescent Inflammatory Bowel Disease: A Systematic Review of Randomized Controlled Trials

A low FODMAP diet (LFD) has been hypothesized to relieve symptoms of functional gastrointestinal disorders (FGD) in patients with inflammatory bowel disease (IBD). The aim of the study was to systematically review the literature for randomized controlled trials (RCTs) assessing the effectiveness of the LFD in patients with IBD and FGD. Four databases were searched, but a meta-analysis was not performed due to methodological and outcomes heterogeneity. Four RCTs fulfilled the criteria, with three having some concerns in their risk of bias assessment. All interventions compared the LFDs against a “typical” or sham diet, spanning in duration from 21 days to 6 weeks. Quality of life was improved in two RCTs, while revealing inconsistent findings in the third trial, based on different assessment tools. The fecal assays revealed non-significant findings for most variables (fecal weight, pH, water content, gene count, and gut transit time) and inconsistent findings concerning stool frequency and short-chain fatty acids concentration. Levels of fecal calprotectin, CRP, or T-cell phenotype did not differ between intervention and comparator arms. Two RCTs reported a reduction in abdominal pain, while results concerning pain duration and bloating were inconsistent. In one trial, energy intake was considerably reduced among LFD participants. Regarding gut microbiota, no differences were noted. A considerable degree of methodological and outcome heterogeneity was observed, paired with results inconsistency. The available data are not sufficient to justify the claim that an LFD induces relief of FGD symptoms, although it may pave the way to a placebo response.