Randomized Open Investigation Determining Steroid Dose in Severe COVID-19: The ROIDS-Dose Clinical Trial.

Introduction Treatment with dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia requiring supplemental oxygen, but the optimal dose has not been determined. Objective To determine whether weight-based dexamethasone of 0.2 mg/kg is superior to 6 mg daily in reducing 28-day mortality in patients with COVID-19 and hypoxemia. Materials and methods A multicenter, open-label, randomized clinical trial was conducted between March 2021 and December 2021 at seven hospitals within Northwell Health. A total of 142 patients with confirmed COVID-19 and hypoxemia were included. Participants were randomized in a 1:1 ratio to dexamethasone 0.2 mg/kg intravenously daily (n = 70) or 6 mg daily (n = 72) for up to 10 days. Results There was no statistically significant difference in the primary outcome of 28-day all-cause mortality with deaths in 12 of 70 patients (17.14%) in the intervention group and 15 of 72 patients (20.83%) in the control group (p = 0.58). There were no statistically significant differences among the secondary outcomes. Conclusion In patients with COVID-19 and hypoxemia, the use of weight-based dexamethasone dosing was not superior to dexamethasone 6 mg in reducing all-cause mortality at 28 days. Clinical trial registration This study was registered under ClinicalTrials.gov (identifier: NCT04834375).

Crohn's Disease Activity Quantified by Iodine Density Obtained From Dual-Energy Computed Tomography Enterography.

OBJECTIVE: The objective of this study was to assess if bowel wall iodine density obtained from dual-source, dual-energy computed tomography enterography (DECTE) could be a biomarker of Crohn's disease activity. METHODS: Twenty-two patients with Crohn's disease imaged with DECTE from February 2016 to May 2018 were retrospectively identified by departmental report search. Iodine maps were created with commercial software (Syngovia). Iodine content was normalized to the aorta, and then manual dual-energy region-of-interest cursors were placed over the visibly assessed maximal and minimal iodine density within segments of involved as well as unaffected small bowel. The mixed Hounsfield unit value, maximum iodine density (Imax), and minimum iodine density (Imin) were recorded. The length of affected bowel demonstrating maximum disease activity as a percentage of overall involvement was subjectively assessed. A weighted iodine density (Iweighted) was calculated. The clinical assessment of disease activity using erythrocyte sedimentation rate, C-reactive protein, fecal calprotectin, colonoscopy/endoscopy, and surgery, if available, served as the reference standard. The Crohn's disease activity index was also used as a separate additional reference standard. RESULTS: Significant heterogeneity within the affected segments was present. The average Imax and Imin of affected bowel was 4.27 ± 1.11 (2.4-7.4) mg/mL and 2.71 ± 0.51 (2.2-3.9) mg/mL, respectively. Iodine density of normal-appearing small bowel was 1.40 ± 0.26 (0.9-1.9) mg/mL. The Imax and Imin of affected bowel differed significantly from normal bowel (P < 0.0001). Mixed Hounsfield unit (101.82 ± 27.5) also statistically differed (46.33 ± 19.62) (P < 0.0001). Using overall clinical assessment as the reference standard, all patients with Imin of greater than 2.6 mg/mL, Iweighted of greater than 3.3 mg/mL, or Imax of greater than 4.7 mg/mL had clinically active disease. Sixteen of 17 patients with Imin of greater than 2.2 mg/mL and 14/15 with Iweighted of greater than 3 mg/mL had clinically active disease. Using Crohn's disease activity index as the reference standard, all patients with Imin of greater than 2.7 mg/mL, Iweighted of greater than 3.6 mg/mL, or Imax of greater than 5.4 mg/mL had clinically active disease. The median effective dose was 4.64 ± 1.68 mSv (range, 2.03-8.12 mSv). CONCLUSIONS: Iodine density obtained from DECTE highlights regions of maximal activity within affected bowel segments. An iodine density of 2 mg/mL appears to be a threshold between normal bowel segments and those with active Crohn's disease. Iodine density measurement thresholds Imin of greater than 2.6 mg/mL, Iweighted of greater than 3.3 mg/mL, and Imax of greater than 4.7 mg/mL correlate with established clinical markers of disease activity, with Imin seemingly most useful in daily clinical practice.

Strongyloides stercoralis Hyperinfection and Concomitant Cytomegalovirus Gastroenteritis in an Immunocompromised Host.

Strongyloides stercoralis infection typically presents with nonspecific gastrointestinal symptoms and no definitive or pathognomonic endoscopic findings. Disease burden can vary depending on a patient's immune status. Immunocompromised patients with strongyloidiasis can develop tremendous disease burden, extraintestinal dissemination, and are at risk for coinfection with other organisms. We present the case of an immunocompromised patient presenting with multiple gastrointestinal complaints found to have S. stercoralis hyperinfection and concomitant cytomegalovirus gastroenteritis.

Outcomes and Management of the Ileal Pouch-Anal Anastomosis in the Elderly.

PURPOSE OF REVIEW: Ileal pouch-anal anastomosis (IPAA) is the preferred surgical treatment for patients undergoing colectomy to maintain intestinal continuity. Earlier studies have suggested that outcomes are worse in elderly patients who underwent IPAA. However, more recent reports have shown that IPAA outcomes in the elderly are comparable to younger patients. We review the recent medical literature regarding outcomes and treatments for common complications in elderly IPAA patients. RECENT FINDINGS: Compared to younger patients, IPAA in the elderly is not associated with increased major surgical complications, but is associated with increased length of stay and re-admission rate for dehydration in older patients. Rates of fecal incontinence after IPAA were similar between younger and older patients. Sacral nerve stimulation has shown early promise as a possible treatment for fecal incontinence after IPAA, but more research is needed. Pouchitis is a common complication, and antibiotics remain first-line treatment options. Other treatment options include mesalamines, steroids, immunomodulators, and biologics. The efficacy of newer biologics such as vedolizumab and ustekinumab has been reported, but more data is needed. IPAA is safe in the elderly with high self-reported patient satisfaction. However, the elderly IPAA patient warrants special consideration regarding outcomes and management.

A Randomized Trial on the Efficacy of Topical Anesthesia for Pain Reduction during Frame Placement for Gamma Knife Radiosurgery.

BACKGROUND/AIMS: Frame application for gamma knife radiosurgery (GKR) may be perceived as painful by patients. This study was designed to assess the efficacy of EMLA (2.5% lidocaine/2.5% prilocaine) in pain reduction. METHODS: This was a prospective, randomized, and controlled trial approved by our institutional review board. Fifty-four patients undergoing outpatient GKR were divided into EMLA and placebo groups. Prior to frame placement, EMLA/placebo was applied to the patient's forehead. A visual analog scale (VAS) was used to measure pain during 4 intervals: frontal injections, occipital injections, frontal screw insertion, and overall discomfort. This study was designed to observe a difference of 1.0 on the VAS at a power of 95%. RESULTS: VAS for EMLA versus placebo for frontal injections (5.2 ± 2.7 vs. 5.7 ± 2.0, respectively; p < 0.45), back injections, (6.5 ± 2.2 vs. 5.9 ± 2.3, respectively; p < 0.30), frontal pins (4.6 ± 2.7 vs. 4.6 ± 2.2, respectively; p < 0.99), and overall discomfort (p < 0.29) were not significantly different. A comparison between back and frontal injections for EMLA (6.54 vs. 5.19, respectively; p < 0.16) and placebo (5.89 vs. 5.68, respectively; p < 0.69) showed no significant difference between group and location (p < 0.21). CONCLUSION: Application of EMLA did not significantly reduce pain when used preoperatively for frame fixation. EMLA is no longer used as part of our routine for patients undergoing GKR.

Role of NMDA, opioid and dopamine D1 and D2 receptor signaling in the acquisition of a quinine-conditioned flavor avoidance in rats.

A conditioned flavor preference (CFP) can be produced by pairing a flavor (conditioned stimulus, CS+) with the sweet taste of fructose. Systemic dopamine (DA) D1, D2 and NMDA, but not opioid, receptor antagonists significantly reduce the acquisition of the fructose-CFP. A conditioned flavor avoidance (CFA) can be produced by pairing a CS+flavor with the bitter taste of quinine. To evaluate whether fructose-CFP and quinine-CFA share common neurochemical substrates, the present study determined the systemic effects of DA D1 (SCH23390: SCH), DA D2 (raclopride: RAC), NMDA (MK-801) or opioid (naltrexone: NTX) receptor antagonists on the acquisition of quinine-CFA. In Experiment 1, food-restricted male rats were trained over 8 alternating one-bottle sessions to drink an 8% fructose+0.2% saccharin solution (FS) mixed with one flavor (CS-, e.g., grape) and a different flavor (CS+, e.g., cherry) mixed in a solution (FSQ) containing fructose+saccharin and quinine at 0.001-0.030% concentrations. In six subsequent two-bottle choice tests (1-3: two sessions each) with the CS- and CS+ flavors presented in FS solutions, only rats trained with 0.03% quinine displayed a CS+ avoidance in Test 1. In Experiment 2, rats received vehicle (Veh), SCH (200 nmol/kg), RAC (200 nmol/kg), MK-801 (100 µg/kg) or NTX (1 mg/kg) 30 min prior to the 8 one-bottle training sessions with CS-/FS and CS+/FSQ (0.03% quinine) solutions. An additional vehicle group (Veh 0.06%) was trained with a CS+/FSQ containing 0.06% quinine. In the two-bottle choice tests, the Veh and RAC groups avoided the CS+ flavor in Test 1 only, whereas the SCH, MK801, and NTX groups significantly avoided the CS+ in Tests 1-3. The Veh.06% group trained avoided the CS+ in Tests 1 and 2, but not Test 3. In Experiment 3, Veh and SCH groups were trained as in Experiment 2, but were tested with CS flavors presented in 0.2% saccharin solutions. The SCH group avoided the CS+ flavor in Tests 1-3 while the Veh group avoided the CS+ in Test 1 only. Thus whereas DA D1, DA D2 and NMDA, but not opioid receptor antagonism blocked acquisition of sweet taste-based CFP, DA D1, NMDA and opioid, but not DA D2 receptor antagonism enhanced the CFA produced by the bitter taste of quinine.

Effect of dopamine D1 and D2 receptor antagonism in the lateral hypothalamus on the expression and acquisition of fructose-conditioned flavor preference in rats.

The attraction to sugar-rich foods is influenced by conditioned flavor preferences (CFP) produced by the sweet taste of sugar (flavor-flavor learning) and the sugar's post-oral actions (flavor-nutrient) learning. Brain dopamine (DA) circuits are involved in both types of flavor learning, but to different degrees. This study investigated the role of DA receptors in the lateral hypothalamus (LH) on the flavor-flavor learning produced the sweet taste of fructose. In an acquisition study, food-restricted rats received bilateral LH injections of a DA D1 receptor antagonist (SCH23390), a D2 antagonist (RAC, raclopride) or vehicle prior to 1-bottle training sessions with a flavored 8% fructose+0.2% saccharin solution (CS+/F) and a less-preferred flavored 0.2% saccharin solution (CS-). Drug-free 2-bottle tests were then conducted with the CS+ and CS- flavors presented in saccharin. The fructose-CFP did not differ among groups given vehicle (76%), 12 nmol SCH (78%), 24 nmol (82%) or 24 nmol RAC (90%) during training. In an expression study with rats trained drug-free, LH injections of 12 or 24 nmol SCH or 12-48 nmol RAC prior to 2-bottle tests did not alter CS+ preferences (77-90%) relative to vehicle injection (86%). Only a 48 nmol SCH dose suppressed the CS+ preference (61%). The minimal effect of LH DA receptor antagonism upon fructose flavor-flavor conditioning differs with the ability of LH SCH injections to block the acquisition of glucose flavor-nutrient learning.