Modified oxygen mask to induce target levels of hyperoxia and hypercarbia during radiotherapy: A more effective alternative to carbogen

Purpose: Carbogen has long been under investigation as an adjuvant to radiotherapy of tumors. A major factor confounding its evaluation is its inconsistency in raising blood partial pressure of CO₂ (pCO₂). We investigated whether a new partial rebreathing method would provide better control of pCO₂ than carbogen.

Methods and materials: We compared the efficacy of each method in 10 healthy volunteers. Volunteers breathed 1.5, 3 and 5% carbogen in 5-min stages via the usual non-rebreathing circuit. All the volunteers then breathed 100% O₂ through a commercial sequential gas delivery (SGD) circuit modified by attaching a reservoir to its exhalation port. Hypercarbia was induced by step reductions in oxygen flow to the SGD circuit. We monitored minute ventilation and end-tidal pCO₂ (ETpCO₂) as a surrogate for its arterial value.

Results: Inhalation of 1.5 and 3% carbogen did not increase ETpCO₂ from baseline (40 ± 1.5 mmHg); 5% carbogen increased ETpCO₂ to 45 ± 1.6 mmHg (p < 0.001). With the SGD circuit, reducing O₂ flow to 4.3 ± 0.7 l/min increased ETpCO₂ in all subjects from 41 ± 2.0 mmHg (baseline) to 46 ± 2.1 mmHg (p < 0.001). Voluntary hyperventilation reduced ETpCO₂ with 5% carbogen but not with SGD (p = 0.379).

Conclusions: We confirm previous observations that carbogen inhalation does not result in a predictable rise in ETpCO₂ and suggest that a precise and stable target ETpCO₂ can instead be induced by simply controlling O₂ flow into a modified SGD circuit. We hoped that the reliable control of pCO₂ will enable studies that address first, the efficacy of raising ETpCO₂ on specific tumor blood flow, and eventually, its benefit as an adjuvant to radiotherapy.     

Long-term prognosis of patients with early post-infarction angina.

BACKGROUND: Most studies have shown that early post-infarction angina (EPA) implies an unfavorable long-term prognosis among patients with acute myocardial infarction (AMI). However, some studies have failed to establish a link between the occurrence of EPA and increased mortality and recurrent infarction rates. METHODS AND RESULTS: In order to evaluate a long-term prognosis in patients with EPA, we assessed the 5-year prognosis of 80 patients with AMI by the presence or absence of EPA. During the 5-year follow up, the occurrence of death, cardiac death, recurrent infarction, unstable angina, heart failure, revascularization and cardiac events were recorded. A cardiac event was defined as an occurrence of any of the following events: cardiac death, recurrent infarction, unstable angina, heart failure and revascularization. Survival analysis showed no differences between patients with and without EPA in the probability of death (p=NS), cardiac death (p=NS), recurrent myocardial infarction (p=NS) and unstable angina (p=NS). Patients with EPA had a higher probability of developing cardiac events (p=0.0285) and undergoing revascularization procedures (p=0.0188). CONCLUSIONS: EPA increases the risk of patients developing cardiac events and undergoing revascularization procedures, and thereby implies a poor long-term prognosis for patients with AMI.     

Level of response to alcohol measured on the self-rating of the effects of alcohol questionnaire in a group of 40-year-old women

A low level of response (LR) to alcohol (i.e., the need for higher amounts to have an effect) is a genetically influenced characteristic that is both found in populations at high risk for future alcoholism and that predicts alcohol-related life problems in the future. A simple paper-and-pencil test that asks subjects to estimate the number of drinks required to produce each of four effects at different times in their lives, the Self-Rating of the Effects of Alcohol (SRE) questionnaire, was developed to facilitate studies of LR. However, data to date on this indirect measure of LR have focused primarily on young male populations. The current study reports SRE values from 121 middle class, middle-aged women who were selected because they were married to men who participated in a longitudinal study of sons of alcoholics and controls. As predicted, the SRE measure of LR, which records the perceived responses of alcohol early in the drinking career (FIRST 5), correlated significantly with recent drinks per drinking day (0.18, p < 0.05), a diagnosis of an alcohol use disorder (0.33, p < 0.001), and with a family history of alcohol dependence (0.20, p < 0.05). The LR value from the SRE reflecting the perceived number of drinks required for effects in the most recent 3 months correlated more closely with both quantity and frequency of drinking (0.36 and higher, p < 0.001), and related to recent nicotine use (0.23, p < 0.05). These data indicate the potential usefulness of the SRE as a measure of LR as a risk factor for alcoholism in relatively highly functioning middle-aged women.     

Specifics of Helicobacter pylori infection/NSAID effects in the elderly

The prevalence of Helicobacter pylori (HP) infection increases with age worldwide. Unlike in younger patients, the presentation of peptic disease in the elderly population is subtle and atypical, and thus leads to a delay of diagnosis. Due to comorbidities and advanced age, it results in increased complications, morbidity and mortality. Bleeding and perforation are frequent complications and therefore peptic ulcer in adult patients represents a serious disease. The relationship between the infection caused by HP and the use of non-steroidal anti-inflammatory drugs (NSAID) in the pathogenesis of peptic ulcer disease is still controversial. However these two factors, independently or in synergy, represent the principal cause of peptic ulcer development in the adult population. In patients diagnosed with peptic ulcer caused by HP, more than half take medications containing aminosalicylic acid. Helicobacter pylori infection in elderly NSAID users is associated with an increased ulcer incidence, but not with an increased prevalence of upper digestive tract bleeding. Helicobacter pylori and NSAID consumption are independent and unrelated risk factors for upper gastrointestinal tract bleeding. Eradication of HP is recommended before the initiation of a long-term aspirin administration in elderly patients. Low aspirin dosages are associated with a high risk of ulcer bleeding. The risk of upper gastrointestinal bleeding in elderly patients is significantly higher in the cases of acute abuse of NSAIDs relative to its chronic use. The simultaneous use of NSAID or aspirin and selective serotonin reuptake inhibitors--antidepressants, increases the risk of upper gastrointestinal bleeding. Peptic ulcer disease in the adult population, if combined with old age, presence of serious and/or life- threatening diseases, as well as repeated ulcer bleedings, shows a high mortality rate.     

The Variants in the 3′ Untranslated Region of the Matrix Metalloproteinase 9 Gene as Modulators of Treatment Outcome in Children with Asthma

Purpose

The maintaining of asthma control is difficult due to high variability in response to therapy among patients. Since matrix metalloproteinase 9 (MMP9) is implicated in inflammation and remodeling of asthmatic airways, it could be associated with adequate response to asthma therapy. The aim of this study was to investigate whether variants in 3′ end of the MMP9 gene are associated with clinical phenotype and responsiveness to treatment in children with asthma.

Methods

The study included 127 asthmatic children from Slovenia. Variants in the 3′ end of the MMP9 gene were analyzed by direct DNA sequencing and the obtained results were correlated with clinical parameters.

Results

Two variants were detected, rs13925 and rs20544. For the variant rs20544, statistically significant difference in airway hyperresponsiveness (p?=?0.011) and asthma control (p?=?0.049) between genotypes was found. Patients with TT genotype had lower airway sensitivity, and after 12 months of treatment showed significant improvement in Asthma Control Test (ACT) scores compared to CC and CT genotype. For the variant rs13925, the association with lung function was observed. The carriers of A allele showed noticeable improvement of lung function after the first 6 months of treatment in comparison to the carriers of G allele (p?=?0.046).

Conclusion

The main finding of our study is the association of MMP9 genotypes rs20544 TT and rs13925 AA and AG with better asthma control, and indirectly better response to treatment. Based on these results, MMP9 deserves further research as a potential predictive biomarker for asthma.

     

Impact of age,race and decade of treatment on overall survival in a critical population analysis of 40,000 multiple myeloma patients

With the availability of novel agents, the overall survival (OS) in patients diagnosed with multiple myeloma (MM) has improved over the last decade. Data on 40,294 MM patients in the years from 1973 to 2003 were obtained from the Surveillance, Epidemiology, and End Results Program (SEER) of the US National Cancer Institute. Statistical analyses evaluating gender, race, age, and year of diagnosis were performed using univariate and multivariate Cox regression models for the OS endpoint. The mean patient age at diagnosis was 68.3 years. Mean survival was 30 months (median = 19 months). Asian/Pacific Islander race was associated with an improved OS, HR 0.90 (CI 0.86–0.95, P < 0.001). American Indian/Alaska Native race was associated with a decreased OS, HR 1.18 (CI 1.01–1.38, P = 0.040). Multivariate analysis did not reveal statistically significant differences in OS between patients in the white and black race (P = 0.709). Younger age (age <65, and 65–75) was associated with improved OS when compared with patients >75 years of age (all P < 0.001). Recent treatment decades (1983–1992 and 1993–2003) were associated with improved OS on multivariate analysis with HR 0.88 (CI 0.88–0.89, P < 0.001) and HR 0.83 (CI 0.81–0.85, P < 0.001), respectively. As the largest population analysis to date, this study reveals a statistically significant improvement in OS for patients who were treated in more recent decades, even before the availability of novel agents. Patients who were <65 years of age and Asian/Pacific Islander race groups exhibited superior levels of OS, whereas American Indian/Alaska Native groups had decreased OS.     

Anterior segment parameters associated with extramuscular manifestations in polymyositis and dermatomyositis

AIM: To evaluate the efficacy and safety of high-dose ultrasound cyclo-plasty (UCP) for the treatment of refractory glaucoma in Chinese patients. METHODS: In this 6-month retrospective study, 37 eyes of 37 patients suffering from severe glaucoma with uncontrolled intraocular pressure (IOP) of ≥21 mm Hg underwent 8-s ultrasonic cyclocoagulation with ten active piezoelectric elements. A complete ophthalmic examination was performed before and at 1d, 1, 3, 6mo after UCP. Therapeutic success was defined as IOP reduction from baseline ≥20% and IOP > 5 mm Hg without adding new glaucoma medication compare to baseline at the 6-month follow-up visit. In addition to mean IOP at each follow-up visit, medications used and complications were also detected and compared to baseline. RESULTS: After UCP procedure, the mean IOP was significantly reduced (P<0.01) from the preoperative 44.1±11.9 mm Hg to postoperative 26.7±11.8 mm Hg at 3mo, and 30.4±14.5 mm Hg at 6mo. The overall mean IOP reductions achieved at 3 and 6mo were 39% and 31%. Sixty-one percent of patients responded well to UCP treatment with a mean IOP reduction of 48% at 3mo and 42% at 6mo. Ocular pain in most of patients were alleviated. No serious intraoperative or postoperative complications occurred. CONCLUSION: High-dose UCP treatment is an effective and safe procedure to reduce IOP in Chinese patients with severe glaucoma.     

Clinical characteristics and functional outcome of patients with West Nile neuroinvasive disease in Serbia

Neurologic manifestations are prominent characteristic of West Nile virus (WNV) infection. The aim of this article was to describe neurological manifestations in patients with WNV neuroinvasive disease and their functional outcome at discharge in the first human outbreak of WNV infection in Serbia. The study enrolled patients treated in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia in Belgrade, with serological evidence of acute WNV infection who presented with meningitis, encephalitis and/or acute flaccid paralyses (AFP). Functional outcome at discharge was assessed using modified Rankin Scale (mRS) and Barthel index. Fifty-two patients were analysed. Forty-four (84.6 %) patients had encephalitis, eight (15.4 %) had meningitis, and 13 (25 %) had AFP. Among patients with AFP, 12 resembled poliomyelitis and one had clinical and electrodiagnostic findings consistent with polyradiculoneuritis. Among patients with encephalitis, 17 (32.7 %) had clinical signs of rhombencephalitis, and eight (15.4 %) presented with cerebellitis. Respiratory failure with subsequent mechanical ventilation developed in 13 patients with WNE (29.5 %). Nine (17.3 %) patients died, five (9.6 %) were functionally dependent (mRS 3–5), and 38 (73.1 %) were functionally independent at discharge (mRS 0–2). In univariate analysis, the presence of AFP, respiratory failure and consciousness impairment were found to be predictors of fatal outcome in patients with WNV neuroinvasive disease (p < 0.001, p < 0.001, p = 0.018, respectively). The outbreak of human WNV infection in Serbia caused a notable case fatality ratio, especially in patients with AFP, respiratory failure and consciousness impairment. Rhombencephalitis and cerebellitis could be underestimated presentations of WNV neuroinvasive disease.