Changes in Orders for Life-Sustaining Treatment in Patients Requiring Prolonged Mechanical Ventilation.

Background: Growing numbers of acute critical illness survivors experience chronic critical illness (CCI) marked by prolonged dependence on life support, delirium, and/or disability. There is minimal recent data on treatment limitations in CCI. Objectives: To evaluate the natural history of changes in orders for life-sustaining treatment (OLST) in patients requiring prolonged mechanical ventilation. Design: Retrospective cohort study of 410 patients who received tracheostomy in an intensive care unit for prolonged respiratory failure. Results: Three hundred twenty-four patients had one OLST throughout the admission, with no limitations on prearrest life-sustaining treatment or cardiopulmonary resuscitation. The 86 patients who underwent at least one change in OLST were older, had longer admissions, were more likely to be deceased at hospital discharge, and were more likely to have received specialty palliative care. Thirty percent of OLST changes occurred in the last week of admission. Conclusions: OLST occur infrequently and late in patients with CCI.

Feeding intolerance in critically ill patients with COVID-19.

BACKGROUND & AIMS: Early reports suggest significant difficulty with enteral feeding in critically ill COVID-19 patients. This study aimed to characterize the prevalence, clinical manifestations, and outcomes of feeding intolerance in critically ill patients with COVID-19. METHODS: We examined 323 adult patients with COVID-19 admitted to the intensive care units (ICUs) of Massachusetts General Hospital between March 11 and June 28, 2020 who received enteral nutrition. Systematic chart review determined prevalence, clinical characteristics, and hospital outcomes (ICU complications, length of stay, and mortality) of feeding intolerance. RESULTS: Feeding intolerance developed in 56% of the patients and most commonly manifested as large gastric residual volumes (83.9%), abdominal distension (67.2%), and vomiting (63.9%). Length of intubation (OR 1.05, 95% CI 1.03-1.08), ≥1 GI symptom on presentation (OR 0.76, 95% CI 0.59-0.97), and severe obesity (OR 0.29, 95% CI 0.13-0.66) were independently associated with development of feeding intolerance. Compared to feed-tolerant patients, patients with incident feeding intolerance were significantly more likely to suffer cardiac, renal, hepatic, and hematologic complications during their hospitalization. Feeding intolerance was similarly associated with poor outcomes including longer ICU stay (median [IQR] 21.5 [14-30] vs. 15 [9-22] days, P < 0.001), overall hospitalization time (median [IQR] 30.5 [19-42] vs. 24 [15-35], P < 0.001) and in-hospital mortality (33.9% vs. 16.1%, P < 0.001). Feeding intolerance was independently associated with an increased risk of death (HR 3.32; 95% CI 1.97-5.6). CONCLUSIONS: Feeding intolerance is a frequently encountered complication in critically ill COVID-19 patients in a large tertiary care experience and is associated with poor outcomes.

Translation of adapting quantitative CT data from research to local clinical practice: validation evaluation of fully automated procedures to provide lung volumes and percent emphysema.

Current clinical chest CT reporting includes limited qualitative assessment of emphysema with rare mention of lung volumes and limited reporting of emphysema, based upon retrospective review of CT reports. Quantitative CT analysis performed in COPDGene and other research cohorts utilize semiautomated segmentation procedures and well-established research method (Thirona). We compared this reference QCT data with fully automated QCT analysis that can be obtained at the time of CT scan and sent to PACS along with standard chest CT images. 164 COPDGene® cohort study subjects enrolled at Brigham and Women's Hospital had baseline and 5-year follow-up CT scans. Subjects included 17 nonsmoking controls, 92 smokers with normal spirometry, 15 preserved ratio impaired spirometry (PRISm) patients, 12 GOLD 1, 20 GOLD 2, and 8 GOLD 3-4. 97% ( n = 319 ) of clinical reports did not mention lung volumes, and 14% ( n = 46 ) made no mention of emphysema. Total lung volumes determined by the fully automated algorithm were consistently 47 milliliters (ml) less than the Thirona reference value for all subjects (95% confidence interval - 62 to - 32 ml ). Percent emphysema values were equivalent to the Thirona reference values. Well-established research reference data can be used to evaluate and validate automated QCT software. Validation can be repeated as software is updated.

Trends in Solid Tumor Incidence in Ukraine 30 Years After Chernobyl.

PURPOSE: There is limited knowledge of the long-term health effects of the Chernobyl nuclear power plant accident that occurred more than 30 years ago in Ukraine. This study describes trends in the incidence of solid organ malignancy in Ukraine and the five regions most affected by the radioactive fallout. METHODS: The National Cancer Registry of Ukraine was queried for age-standardized incidence rates (ASIRs) of solid organ malignancy in Ukraine and the regions of Kyiv, Chernihiv, Zhytomyr, Rivne, and Volyn covering the period of 1999 to 2016. Joinpoint analysis was used to calculate the average annual percentage of change. RESULTS: The highest burdens of cancer incidence in Ukraine were seen in the lung, stomach, breast, and prostate. We observed significant increases in the ASIRs of colon (average annual percentage of change, 1.5 [95% CI, 1.3 to 1.7]), rectal (0.9 [95% CI, 0.6 to 1.2]), kidney (2.3 [95% CI, 1.8 to 2.9]), thyroid (4.2 [95% CI, 3.1 to 5.3]), breast (1 [95% CI, 0.6 to 1.4]), cervical (0.7 [95% CI, 0.3 to 1.2]), and prostate (3.9 [95% CI, 3.6 to 4.2]) cancers, with decreases in stomach (-2.4 [95% CI, -2.5 to -2.3]) and lung (-1.8 [95% CI, -2.1 to -1.5]) cancers. ASIRs in the affected regions were similar to nationwide rates, with the exception of those for Kyiv. CONCLUSION: The incidence rates of many solid organ malignancies in Ukraine are rising. However, the rates of solid organ malignancy in the five regions most affected by fallout did not substantially differ from national patterns, with the exception of those for Kyiv. Ongoing monitoring of cancer incidence in Ukraine is necessary to understand how best to decrease disease burden nationwide and to elucidate the causes of regional variations in ASIRs, such as access to diagnostics and environmental exposures.

Blockade of RGMb inhibits allergen-induced airways disease.

BACKGROUND: Allergic asthma causes morbidity in many subjects, and novel precision-directed treatments would be valuable. OBJECTIVE: We sought to examine the role of a novel innate molecule, repulsive guidance molecule b (RGMb), in murine models of allergic asthma. METHODS: In models of allergic asthma using ovalbumin or cockroach allergen, mice were treated with anti-RGMb or control mAb and examined for airway inflammation and airway hyperreactivity (AHR), a cardinal feature of asthma. The mechanisms by which RGMb causes airways disease were also examined. RESULTS: We found that blockade of RGMb by treatment with anti-RGMb mAb effectively blocked the development of airway inflammation and AHR. Importantly, blockade of RGMb completely blocked the development of airway inflammation and AHR, even if treatment occurred only during the challenge (effector) phase. IL-25 played an important role in these models of asthma because IL-25 receptor-deficient mice did not develop disease after sensitization and challenge with allergen. RGMb was expressed primarily by innate cells in the lungs, including bronchial epithelial cells (known producers of IL-25), activated eosinophils, and interstitial macrophages, which in the inflamed lung expressed the IL-25 receptor and produced IL-5 and IL-13. We also found that neogenin, the canonical receptor for RGMb, was expressed by interstitial macrophages and bronchial epithelial cells in the inflamed lung, suggesting that an innate RGMb-neogenin axis might modulate allergic asthma. CONCLUSIONS: These results demonstrate an important role for a novel innate pathway in regulating type 2 inflammation in patients with allergic asthma involving RGMb and RGMb-expressing cells, such as interstitial macrophages and bronchial epithelial cells. Moreover, targeting this previously unappreciated innate pathway might provide an important treatment option for allergic asthma.

Outcomes of Abdominal Surgery in Patients With Mechanical Ventricular Assist Devices: A Multi-institutional Study.

OBJECTIVE: The aim of this study was to examine the outcomes of elective and emergent abdominal operations performed in end-stage heart failure patients supported with ventricular assist devices (VADs). SUMMARY OF BACKGROUND DATA: With the growing volume of end-stage heart failure patients receiving VADs, an increasing number of these patients require surgery for noncardiac pathology. There is a paucity of studies on the safety of abdominal operations in this population. METHODS: We performed a retrospective chart review across 3 hospitals of patients with VADs who underwent abdominal surgeries between 2003 and 2015. We used Chi-square, Fisher exact, and Mann-Whitney U tests for comparison of elective and emergent cases. RESULTS: Fifty-seven patients underwent 63 operations, of which 23 operations were elective, 24 were emergent, and 16 were emergently performed in the same admission as VAD placement and analyzed separately. Patients undergoing elective versus emergent procedures had similar comorbidities (Charlson score 2.9 vs 3.0). 43% versus 32% of patients had VADs as a destination therapy. Although perioperative anticoagulation approach was variable, holding warfarin and starting heparin/enoxaparin/bivalirudin bridge was most common (65% vs 54%). Although 2-fold higher in the emergent group (50 vs 100 mL, P = 0.06), median estimated blood loss was low. Postoperative bleeding requiring transfusion was not very common (13% vs 8%), whereas rate of ischemic cerebrovascular accident (4% each) and venous thromboembolism was low (0% vs 13%, P = 0.23). Thirty-day mortality rate was 4% versus 17%, P = 0.19. CONCLUSION: VAD patients have an acceptable risk profile for abdominal surgery.