Management and outcomes of acute respiratory distress syndrome patients with and without comorbid conditions

Rationale

The standard of care for patients with acute respiratory distress syndrome (ARDS) has been developed based on studies that usually excluded patients with major comorbidities.

Objectives

To describe treatments and outcomes according to comorbidities in patients with ARDS admitted to 19 ICUs (1997–2014).

Methods

Patients were grouped based on comorbidities. Determinants of day-28 mortality were identified by multivariable Cox analysis stratified on center.

Measurements and main results

Among 4953 ARDS patients, 2545 (51.4%) had major comorbidities; the proportion with major comorbidities increased after 2008. Hematological malignancy was associated with severe ARDS and rescue therapies for refractory hypoxemia. COPD, HIV infection, and hematological malignancy were associated with a lower likelihood of invasive mechanical ventilation on the admission day. Admission-day SOFA score was higher in patients with major comorbidities, who more often received vasopressors, dialysis, or treatment-limitation decisions. Day-28 mortality was 33.7% overall, 27.2% in patients without major comorbidities, and 31.1% (COPD) to 56% (hematological malignancy) in patients with major comorbidities. By multivariable analysis, mortality was lower in patients with COPD and higher in those with chronic heart failure, solid tumors, or hematological malignancies. Mortality was independently associated with P_aO₂/F_iO₂ and PaCO₂ on day 1, ARDS of pulmonary origin, worse SOFA score, and ICU-acquired events.

Conclusions

Half the patients with ARDS had major comorbidities, which were associated with severe ARDS, multiple organ dysfunction, and day-28 mortality. These findings do not support the exclusion of ARDS patients with severe comorbidities from randomized clinical trials. Trials in ARDS patients with whatever comorbidities are warranted.

     

Thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation: an autopsy study

BACKGROUND: Posttransplantation thrombotic microangiopathy (PTMA) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT). However, limited autopsy data are available, and it remains unclear whether PTMA is a discrete clinical and pathologic entity. The aims of this autopsy study were to determine the correlation between clinical and pathologic diagnosis of PTMA, to define the precise morphologic spectrum of PTMA, and to seek for potential etiologic factors. METHODS: The study included 20 consecutive patients with HSCT autopsied at the University of Oklahoma, between 1994 and 2005. Applying strict clinical-laboratory criteria, 6 patients were diagnosed clinically with PTMA and treated with plasma exchange. Clinical variables, including underlying disease, conditioning regimen, stem cell donor status, duration and serum level of cyclosporine, infections, and acute graft versus host disease were compared statistically in patients with histologic signs of PTMA (n=8) with those without PTMA (n=12). RESULTS: PTMA was verified histologically in all 6 patients with a clinical diagnosis of PTMA but only 2 of the 14 patients who were not clinically diagnosed had histologic evidence of PTMA (P<0.0001). Kidneys were affected in all 8 patients with PTMA, and limited extrarenal involvement by PTMA was observed in 3 of these 8 patients. No statistically significant differences in relevant clinical and morphologic variables were identified between the PTMA and non-PTMA groups. CONCLUSIONS: This study documents a strong correlation between the clinical and morphologic diagnosis of PTMA. The kidney is the primary target of PTMA, with dominant glomerular and arteriolar involvement. The etiology is likely to be multifactorial.     

Anti‐atherogenic effects of high‐density lipoprotein on nitric oxide synthesis in the endothelium

1. The endothelium is critical in the control of vascular haemodynamics and haemostasis. Endothelial dysfunction, typically characterized by decreased nitric oxide bioavailability and response to endothelium‐dependent agonists, is well accepted as a defining characteristic of early atherosclerosis. 2. Numerous epidemiological studies have reported that increased levels of circulating HDL are vasculoprotective and reduce the incidence of adverse cardiovascular events. Traditionally, these effects have been attributed to the ability of HDL to remove cholesterol from cells via reverse cholesterol transport. However, there is increasing evidence that the beneficial effects on the endothelium by HDL encompass its anti‐inflammatory, antithrombotic and anti‐oxidative properties, which include the release of nitric oxide (NO). 3. This review highlights recent findings on the importance of HDL in reducing atherosclerotic risk. We focus on the beneficial effects of HDL‐induced NO release and how this relates to endothelial dysfunction and on the effect of HDL on vascular repair via endothelial progenitor cells.     

Inheritance in idiopathic premature ovarian failure: analysis of 71 cases

Premature ovarian failure is defined as cessation of ovarian function under the age of 40 years and affects approximately 1% of women in the general population. The aetiology of this disorder is still unknown in most cases. Although there have been some reports of familial premature ovarian failure, very little is known about the incidence and inheritance pattern of its idiopathic form. The aims of this study were to investigate the incidence and inheritance pattern of familial premature ovarian failure in a homogeneous group of patients with premature idiopathic menopause and to identify possible clinical differences between patients with the familial and the sporadic form of premature ovarian failure. A total of 71 women were recruited into the study. Clinical assessments and genetic counselling showed that 22 (31%) patients had familial premature ovarian failure, this high incidence strongly suggesting that the disorder is a recognizable heritable entity. There was a statistically significant (P < 0.05) difference in the median age of precocious menopause in patients with sporadic and familial premature ovarian failure (31.0 and 37.5 years of age in the two groups, respectively). Pedigree analysis strongly suggests the existence of a familial pattern of premature ovarian failure with a dominant maternal and/or paternal transmission and incomplete penetrance. In the presence of familial history of premature ovarian failure, reproductive counselling is recommended.      

Diagnostic imaging of human neuroblastoma with radiolabeled antibody

In a previous study, the authors showed that iodine-131 labeled monoclonal antibody (Mab 3F8) could be used to image human neuroblastoma xenografts in mice with excellent tumor-to-tissue ratios. In this study they report their experience with six patients scanned with radiolabeled 3F8. There was strong accumulation of the labeled antibody in viable tumor, but no significant uptake was noted in normal brain, liver, spleen, or adrenal glands. Tumor-to-nontumor activity ratios varied but were approximately 10:1-20:1. This ratio yields good contrast for visualization. Time-activity curves show that radioactivity levels in normal tissue have a half-time of about 40 hours, whereas tumor tissues show a half-time of about 60 hours. Significant gastric secretion of free iodine demonstrated that the Mab was being deiodinated. Calculated radiation doses indicate that tumors receive at least ten times the dose to other tissues. The results indicate that Mab 3F8 has clinical potential for both imaging and therapy of human neuroblastomas.     

Differential responses of granulosa cells from small and large follicles to follicle stimulating hormone (FSH) during the menstrual cycle and acyclicity: effects of tumour necrosis factor-alpha

This study determined effects of follicle stimulating hormone (FSH) alone and in combination with tumour necrosis factor (TNF), on granulosa cells from small (5-10 mm diameter) and large (>10-25 mm) follicles during follicular and luteal phases of the cycle and during periods of acyclicity. Granulosa cells were collected from ovaries of premenopausal women undergoing oophorectomy. The cells were cultured with human FSH (2 ng/ml) and testosterone (1 microM) in the presence or absence of human TNF-alpha (20 ng/ml). Media were removed at 48 and 96 h after culture and progesterone, oestradiol and cAMP in media were measured by radioimmunoassays. FSH stimulated the accumulation of oestradiol from granulosa cells of small follicles during the follicular and luteal phases but not during acyclicity; and TNF reduced oestradiol accumulation in the presence of FSH. Interestingly, in granulosa cells from small follicles, progesterone and cAMP secretion increased in response to FSH and neither was affected by TNF. Thus, TNF specifically inhibited the conversion of testosterone to oestradiol in granulosa cells from small follicles. FSH stimulated oestradiol production by granulosa cells of large follicles obtained only during the follicular phase of the cycle and TNF inhibited the FSH-induced oestradiol secretion. Granulosa cells obtained from large follicles during the luteal phase and during acyclicity did not accumulate oestradiol in response to FSH. However, FSH increased progesterone and cAMP secretion by granulosa cells obtained from large follicles during the follicular and luteal phases. During the luteal phase alone, TNF in combination with FSH increased progesterone accumulation above that of FSH alone. FSH did not increase progesterone, oestradiol or cAMP secretion by granulosa cells obtained from large follicles during acyclicity. Thus, FSH increases progesterone, oestradiol and cAMP secretion by granulosa cells of small follicles during the follicular and luteal phases and TNF appears to inhibit FSH-induced oestradiol secretion specifically in those cells. In large follicles, FSH- stimulated granulosa cell secretion of oestradiol is limited to the follicular phase and this effect can be inhibited by TNF. In addition, when granulosa cells of large follicles do not increase oestradiol secretion in response to FSH, TNF stimulates progesterone secretion.