A comparison of intravenous methylprednisolone and hydrocortisone for the treatment of acute inflammatory bowel disease.

BACKGROUND AND AIM: Despite widespread recommendations and use of intravenous corticosteroids (IVCS) for the treatment of acute flares of ulcerative colitis and Crohn's disease, limited evidence exists comparing outcomes of the two most common regimens, intravenous methylprednisolone (IVMP) and intravenous hydrocortisone (IVHC). IVHC has stronger mineralocorticoid effects compared with IVMP and may cause higher rates of hypokalemia. We aimed to determine differences in clinical outcomes including requirement for inpatient rescue therapy, bowel resection, and rates of hypokalemia. METHODS: We conducted a multicenter cohort study of all adult patients admitted with an acute flare of inflammatory bowel disease (IBD) to the three tertiary hospitals in Auckland, New Zealand, where the protocol at each institution is either IVMP 60 mg daily or IVHC 100 mg four times daily. All patients requiring IVCS between 20 June 2016 and 30 June 2018 were included. The IVCS protocol was then changed at one hospital, where further data were collected for a further 12 months from 30 January 2019 until 30 December 2019. RESULTS: There were 359 patients, including 129 (35.9%) patients receiving IVMP and 230 (64.1%) patients receiving IVHC. IVMP treatment was associated with a greater requirement for rescue therapy than IVHC (36.4% vs 19.6%, P = 0.001; odds ratio [OR] = 2.79; 95% confidence interval [CI], 1.64-4.75, P < 0.001), but also reduced rates of hypokalemia (55.8% vs 67.0%, P = 0.04; OR = 0.49; 95% CI, 0.30-0.81, P = 0.005). There was no difference between treatment groups for the median length of admission (5 days, interquartile range [IQR] 3-8), median duration of IVCS treatment (3 days, IQR 2-5), or bowel resection within 30 days of admission (12.4% vs 11.7%; OR = 1.04). CONCLUSION: For the treatment of an acute flare of IBD, treatment with IVMP results in significantly more requirement for inpatient rescue biologic or cyclosporin. In addition, it causes statistically significant less hypokalemia than IVHC, although in practice differences are negligible.

An observational study of feeding practice in ventilated patients with spinal cord injury.

BACKGROUND AND AIMS: Cervical spinal cord injuries (CSCI) are frequently complicated by respiratory failure requiring prolonged invasive mechanical ventilation in the intensive care unit (ICU). Providing adequate nutrition may be an important factor in the recovery of respiratory muscle function for ventilator weaning. The aim of this study was to examine the practical implementation of a multi-disciplinary approach to nutrition combining indirect calorimetry and the modified Harris Benedict equation to achieve target rates of nutrition for patients with CSCI. MATERIALS AND METHODS: A retrospective observational study was performed by collecting data of normal nutrition practice in a series of adult ventilated patients with CSCI admitted between 2014 and 2017 to the ICU. Administered calories by enteral nutrition and measured total energy expenditure (TEE) by indirect calorimetry were recorded for the first 3-weeks. Calculations were performed to measure the adequacy of calorie administration relative to TEE. Average daily temperatures and minute ventilation were recorded to support evidence for hypermetabolism. TEE estimates using the modified Harris Benedict equation were compared to indirect calorimetry measures for each patient. RESULTS: Sixteen patients were included in the study. Calorie administration rapidly increased to a plateau of 2300-2400 kcal per day over the first four days. The median measured TEE by indirect calorimetry was initially high, starting at 3472 kcal/day and decreasing to 2784 kcal/day at three weeks. However, there was wide variation in energy expenditure amongst patients. Average daily temperatures and minute ventilation were high supporting hypermetabolism. Adequacy of calorie administration to TEE ranged between 76 and 86 percent through the study period. There was relatively wide variation when comparing estimates of TEE using the modified Harris Benedict equation versus indirect calorimetry. CONCLUSIONS: A multi-disciplinary approach to nutrition in ventilated patients with CSCI, incorporating indirect calorimetry, achieves target rates of nutrition. Our findings suggest that a hypermetabolic response may be common but variable in this population and subsequently both under and over feeding may be a risk if nutrition targets are not guided by indirect calorimetry. Further prospective research using protocoled indirect calorimetry measures would be beneficial to ascertain accurate energy requirements for this group of patients and also determine whether feeding to target influences weaning off the ventilator.

Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy.

Tumor relapse after chemotherapy-induced regression is a major clinical problem, because it often involves inoperable metastatic disease. Tumor-associated macrophages (TAM) are known to limit the cytotoxic effects of chemotherapy in preclinical models of cancer. Here, we report that an alternatively activated (M2) subpopulation of TAMs (MRC1(+)TIE2(Hi)CXCR4(Hi)) accumulate around blood vessels in tumors after chemotherapy, where they promote tumor revascularization and relapse, in part, via VEGF-A release. A similar perivascular, M2-related TAM subset was present in human breast carcinomas and bone metastases after chemotherapy. Although a small proportion of M2 TAMs were also present in hypoxic tumor areas, when we genetically ablated their ability to respond to hypoxia via hypoxia-inducible factors 1 and 2, tumor relapse was unaffected. TAMs were the predominant cells expressing immunoreactive CXCR4 in chemotherapy-treated mouse tumors, with the highest levels expressed by MRC1(+) TAMs clustering around the tumor vasculature. Furthermore, the primary CXCR4 ligand, CXCL12, was upregulated in these perivascular sites after chemotherapy, where it was selectively chemotactic for MRC1(+) TAMs. Interestingly, HMOX-1, a marker of oxidative stress, was also upregulated in perivascular areas after chemotherapy. This enzyme generates carbon monoxide from the breakdown of heme, a gas known to upregulate CXCL12. Finally, pharmacologic blockade of CXCR4 selectively reduced M2-related TAMs after chemotherapy, especially those in direct contact with blood vessels, thereby reducing tumor revascularization and regrowth. Our studies rationalize a strategy to leverage chemotherapeutic efficacy by selectively targeting this perivascular, relapse-promoting M2-related TAM cell population.