Respiratory mechanical effects of surgical pneumoperitoneum in humans.

Pneumoperitoneum for laparoscopic surgery is known to stiffen the chest wall and respiratory system, but its effects on resting pleural pressure in humans are unknown. We hypothesized that pneumoperitoneum would raise abdominal pressure, push the diaphragm into the thorax, raise pleural pressure, and squeeze the lung, which would become stiffer at low volumes as in severe obesity. Nineteen predominantly obese laparoscopic patients without pulmonary disease were studied supine (level), under neuromuscular blockade, before and after insufflation of CO2 to a gas pressure of 20 cmH2O. Esophageal pressure (Pes) and airway pressure (Pao) were measured to estimate pleural pressure and transpulmonary pressure (Pl = Pao - Pes). Changes in relaxation volume (Vrel, at Pao = 0) were estimated from changes in expiratory reserve volume, the volume extracted between Vrel, and the volume at Pao = -25 cmH2O. Inflation pressure-volume (Pao-Vl) curves from Vrel were assessed for evidence of lung compression due to high Pl. Respiratory mechanics were measured during ventilation with a positive end-expiratory pressure of 0 and 7 cmH2O. Pneumoperitoneum stiffened the chest wall and the respiratory system (increased elastance), but did not stiffen the lung, and positive end-expiratory pressure reduced Ecw during pneumoperitoneum. Contrary to our expectations, pneumoperitoneum at Vrel did not significantly change Pes [8.7 (3.4) to 7.6 (3.2) cmH2O; means (SD)] or expiratory reserve volume [183 (142) to 155 (114) ml]. The inflation Pao-Vl curve above Vrel did not show evidence of increased lung compression with pneumoperitoneum. These results in predominantly obese subjects can be explained by the inspiratory effects of abdominal pressure on the rib cage.

CEPP regimen (cyclophosphamide, etoposide, procarbazine and prednisone) as initial treatment for Hodgkin lymphoma patients presenting with severe abnormal liver function.

ABVD regimen (doxorubicin, bleomycin, vinblastine and dacarbazine) remains the most commonly used front-line therapy for Hodgkin lymphoma. However, atypical and extranodal presentations present challenges to initial therapy, especially in the presence of renal and liver failure. We hereby present two cases of young male patients with atypical presentation of Hodgkin lymphoma with severe abnormal liver function. Patients showed excellent response to cyclophosphamide, etoposide, procarbazine and prednisone (CEPP regimen).

Ibrutinib for B cell malignancies.

Research over the role of Bruton's agammaglobulinemia tyrosine kinase (BTK) in B-lymphocyte development, differentiation, signaling and survival has led to better understanding of the pathogenesis of B-cell malignancies. Down-regulation of BTK activity is an attractive novel strategy for treating patients with B-cell malignancies. Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site of BTK (TH/SH1 domain) and inhibits BTK phosphorylation on Tyr223. This review discussed in details the role of BTK in B-cell signaling, molecular interactions between B cell lymphoma/leukemia cells and their microenvironment. Clinical trials of the novel BTK inhibitor, ibrutinib (PCI-32765), in B cell malignancies were summarized.

Pleural pressure and optimal positive end-expiratory pressure based on esophageal pressure versus chest wall elastance: incompatible results*.

OBJECTIVES: 1) To compare two published methods for estimating pleural pressure, one based on directly measured esophageal pressure and the other based on chest wall elastance. 2) To evaluate the agreement between two published positive end-expiratory pressure optimization strategies based on these methods, one targeting an end-expiratory esophageal pressure-based transpulmonary pressure of 0 cm H2O and the other targeting an end-inspiratory elastance-based transpulmonary pressure of 26 cm H2O. DESIGN: Retrospective study using clinical data. SETTING: Medical and surgical ICUs. PATIENTS: Sixty-four patients mechanically ventilated for acute respiratory failure with esophageal balloons placed for clinical management. METHODS: Esophageal pressure and chest wall elastance-based methods for estimating pleural pressure and setting positive end-expiratory pressure were retrospectively applied to each of the 64 patients. In patients who were ventilated at two positive end-expiratory pressure levels, chest wall and respiratory system elastances were calculated at each positive end-expiratory pressure level. MEASUREMENTS AND MAIN RESULTS: The pleural pressure estimates using both methods were discordant and differed by as much as 10 cm H2O for a given patient. The two positive end-expiratory pressure optimization strategies recommended positive end-expiratory pressure changes in opposite directions in 33% of patients. The ideal positive end-expiratory pressure levels recommended by the two methods for each patient were discordant and uncorrelated (R = 0.05). Chest wall and respiratory system elastances grew with increases in positive end-expiratory pressure in patients with positive end-expiratory esophageal pressure-based transpulmonary pressures (p < 0.05). CONCLUSIONS: Esophageal pressure and chest wall elastance-based methods for estimating pleural pressure do not yield similar results. The strategies of targeting an end-expiratory esophageal pressure-based transpulmonary pressure of 0 cm H2O and targeting an end-inspiratory elastance-based transpulmonary pressure of 26 cm H2O cannot be considered interchangeable. Finally, chest wall and respiratory system elastances may vary unpredictably with changes in positive end-expiratory pressure.

Patients with celiac disease have a lower prevalence of non-insulin-dependent diabetes mellitus and metabolic syndrome.

BACKGROUND & AIMS: We investigated whether risk for non-insulin-dependent diabetes mellitus (NIDDM) and metabolic syndrome are affected by celiac disease. We examined the prevalence of NIDDM and metabolic syndrome among adults with celiac disease, compared with matched controls. METHODS: We assessed medical records of 840 patients with biopsy-proven celiac disease for diagnoses of NIDDM, hypertension, or hyperlipidemia; body mass index (BMI); lipid profile; and levels of glucose or glycosylated hemoglobin, to identify those with metabolic syndrome. Patients without celiac disease were matched for age, sex, and ethnicity (n = 840 controls). The prevalence of NIDDM and metabolic syndrome in the celiac disease cohort was compared with that of the controls and subjects included in the National Health and Nutrition Examination Survey. RESULTS: Twenty-six patients with celiac disease (3.1%) had NIDDM compared with 81 controls (9.6%) (P < .0001). Similarly, the prevalence of metabolic syndrome was significantly lower among patients with celiac disease than controls (3.5% vs 12.7%; P < .0001). The mean BMI of patients with celiac disease was significantly lower than that of controls (24.7 vs 27.5; P < .0001). However, celiac disease was still associated with a lower risk of NIDDM, after controlling for BMI. CONCLUSIONS: The prevalence of NIDDM and metabolic syndrome are lower among patients with celiac disease than in matched controls and the general population. These differences are not explained by differences in BMI. Studies are needed to determine the mechanisms by which celiac disease affects the risk for NIDDM and metabolic syndrome.

Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats.

BACKGROUND: Cholesterol may have a role in the pathophysiology of depression. Lowering cholesterol levels with statins reduces risks for cardiovascular events, and there is clinical evidence that statins exert neuroprotective properties not fully explained by their effects on serum cholesterol levels. Altered cholesterol levels can affect serotonergic neurotransmission, which might be involved in the clinical efficacy of standard antidepressants. METHODS: We examined interactions between a statin (lovastatin) and a selective serotonin reuptake inhibitor (fluoxetine) using the forced swim test (FST) in rats, a behavioral assay that identifies treatments with antidepressant effects in humans. Specifically, we determined if the addition of lovastatin to the diet would increase the efficacy of a subeffective dose of fluoxetine. RESULTS: Rats maintained on a lovastatin-enriched diet for 30 days were more sensitive to the antidepressant-like effects of a low (subthreshold) dose of fluoxetine. The behavior of rats treated with this combination resembled that normally seen with higher doses of fluoxetine. No effects were observed in rats maintained on a lovastatin-enriched diet for 3 days. CONCLUSIONS: Lovastatin can augment the antidepressant-like effects of a low dose of fluoxetine in rats, raising the possibility that statins could be used to facilitate the effects of antidepressants in humans.