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Background: Photobiomodulation therapy (PBMT) using devices to deliver red and/or near-infrared light to tissues has shown promising effects in clinical settings for respiratory diseases, including potential benefits in managing symptoms associated with COVID-19. Objective: To determine if at-home self-administered PBMT for patients with COVID-19 is safe and effective. Methods: This was a randomized controlled trial (RCT) carried out at home during the COVID-19 pandemic (September 2020 to August 2021). The treatment group self-administered the Vielight RX Plus PBMT device (635 nm intranasal and 810 nm chest LEDs) and were monitored remotely. Eligible patients scored 4-7 (out of 7) for severity on the Wisconsin Upper Respiratory Symptom Survey (WURSS-44). Patients were randomized equally to Control group receiving standard-of-care (SOC) only or Treatment group receiving SOC plus PBMT. The device was used for 20 min 2X/day for 5 days and, subsequently, once daily for 30 days. The primary end-point was time-to-recovery (days) based on WURSS-44 question 1, "How sick do you feel today?". Subgroup analysis was performed, and Kaplan-Meier and Cox Proportional Hazards analysis were employed. Results: One hundred and ninety-nine eligible patients (18-65 years old) were divided into two subgroups as follows: 136 patients with 0-7 days of symptoms at baseline and 63 patients with 8-12 days of symptoms. Those with 0-7 days of symptoms at baseline recovered significantly faster with PBMT. The median for Treatment group was 18 days [95% confidence interval (CI), 13-20] versus the Control group 21 days (95% CI, 15-28), p = 0.050. The treatment:control hazard ratio was 1.495 (95% CI, 0.996-2.243), p = 0.054. Patients with symptom duration ≥7 days did not show any significant improvement. No deaths or severe adverse events (SAEs) occurred in the Treatment group, whereas there was 1 death and 3 SAEs requiring hospitalization in the Control group. Conclusions: Patients with ≤7 days of COVID-19 symptoms recovered significantly faster with PBMT compared to SOC. Beyond 7 days, PBMT showed no superiority over SOC. Trial Registration: ClinicalTrials.gov NCT04418505.

Purpose: [ 18 F]SF51 was previously found to have high binding affinity and selectivity for 18 kDa translocator protein (TSPO) in mouse brain. This study sought to assess the ability of [ 18 F]SF51 to quantify TSPO in rhesus monkey brain., Methods: Positron emission tomography (PET) imaging was performed in monkey brain (n = 3) at baseline and after pre-blockade with the TSPO ligands PK11195 and PBR28. TSPO binding was calculated as total distribution volume corrected for free parent fraction in plasma (V T /f P ) using a two-tissue compartment model. Receptor occupancy and nondisplaceable uptake were determined via Lassen plot. Binding potential (BP ND ) was calculated as the ratio of specific binding to nondisplaceable uptake. Time stability of V T was used as an indirect probe to detect radiometabolite accumulation in the brain. In vivo and ex vivo experiments were performed in mice to determine the distribution of the radioligand., Results: After [ 18 F]SF51 injection, the concentration of brain radioactivity peaked at 2.0 standardized uptake value (SUV) at ~ 10 min and declined to 30% of the peak at 180 min. V T /f P at baseline was generally high (203 ± 15 mL· cm -3 ) and decreased by ~ 90% after blockade with PK11195. BP ND of the whole brain was 7.6 ± 4.3. V T values reached levels similar to terminal 180-min values by 100 min and remained relatively stable thereafter with excellent identifiability (standard errors < 5%), suggesting that no significant radiometabolites accumulated in the brain. Ex vivo experiments in mouse brain showed that 96% of radioactivity was parent. No significant uptake was observed in the skull, suggesting a lack of defluorination in vivo., Conclusion: The results demonstrate that [ 18 F]SF51 is an excellent radioligand that can quantify TSPO with a good ratio of specific to nondisplaceable uptake and has minimal radiometabolite accumulation in brain. Collectively, the results suggest that [ 18 F]SF51 warrants further evaluation in humans., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Patients with cystic fibrosis (CF) and pancreatic insufficiency are at risk for suboptimal fat absorption, inability to maintain weight, poor growth, and increased gastrointestinal (GI) symptoms due to malabsorption. Enteral nutrition (EN) is used to supplement caloric intake and requires pancreatic enzyme replacement for effective digestion. We evaluated the relationship between long-term use of an in-line digestive enzyme cartridge with EN and changes in anthropometric measures and GI symptoms in patients with CF., Methods: This is a single-center, retrospective case review of patients with CF using a digestive enzyme cartridge with EN. Data were collected from the patient medical records and included weight, height, body mass index, EN regimen, and reported GI symptoms., Results: Thirteen pediatric and five adult patients with a mean age of 12.6 years used a digestive enzyme cartridge with EN for a period of 3-27 months. Most patients (n = 14) had been using oral digestive enzymes with EN before using the digestive enzyme cartridge, whereas four started from the onset of EN. The indications to convert from oral enzymes to the digestive enzyme cartridge included poor growth (72.2%) and poor tolerance of EN (69.2%). There was a reduction in reported GI symptoms after initiating use of the digestive enzyme cartridge. After 12 months of digestive cartridge use, there were improvements in anthropometrics., Conclusions: This real-world experience with prolonged use of a digestive enzyme cartridge with EN demonstrated improved clinical outcomes and a reduction in GI symptoms in patients with CF., (© 2022 American Society for Parenteral and Enteral Nutrition.)

Background: The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone., Patients and Methods: Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases. The primary tumor side data were prospectively collected. The principal outcome measure was overall survival (OS) stratified by treatment and primary tumor side., Results: In the combined analysis of all 739 patients enrolled, SIRT had no effect on OS (median OS, 24.3 vs. 24.6 months; hazard ratio [HR], 1.021; P = .810). For the 179 patients (24.2%) with a RSP tumor, OS was improved with the addition of SIRT (median, 22.0 vs. 17.1 months HR, 0.641; P = .008). The addition of SIRT was not associated with a significant difference in OS among the 540 patients with a LSP tumor (median, 24.6 vs. 26.6 months; HR, 1.120; P = .264). A test of treatment interaction by primary tumor side was statistically significant for RSP and SIRT (P = .002)., Conclusion: The addition of SIRT for patients with RSP tumors, but not for those with LSP tumors, was associated with a statistically and clinically significant OS gain., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation., Methods: This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records., Results: Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1-45.9) versus 30.9 months (19.6-46.8); p = 0.243); stage B: 18.4 months (11.2-19.4) versus 22.8 months (10.9-34.2); p = 0.815; and stage C: 8.8 months (7.1-10.8) versus 10.8 months (7.7-12.6); p = 0.976., Conclusions: Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.

Purpose To determine if high lung shunt fraction (LSF) is an independent prognostic indicator of poor survival in patients who undergo yttrium 90 radioembolization for unresectable liver-dominant metastatic colorectal cancer. Materials and Methods Retrospective data were analyzed from 606 patients (62% men; mean age, 62 years) who underwent radioembolization to treat liver metastases from colorectal adenocarcinoma between July 2002 and December 2011 at 11 U.S. centers. Institutional review board exemptions were granted prior to the collection of data at each site. Overall survival was estimated by using Kaplan-Meier survival and univariate Cox proportional hazards models to examine the effect of LSF on survival and to compare this to other potential prognostic indicators. Multivariate analysis was also performed to determine whether LSF is an independent risk factor for poor survival. Results LSF higher than 10% was predictive of significantly decreased survival (median, 6.9 months vs 10.0 months; hazard ratio, 1.60; P < .001) and demonstrated a mild but significant correlation to serum carcinoembryonic antigen levels and tumor-to-liver volume ratio (Pearson correlation coefficients, 0.105 and 0.113, respectively; P < .05). A progressive decrease in survival was observed as LSF increased from less than 5% to more than 20% (P < .05). LSF did not correlate with the presence of extrahepatic metastases or prior administration of bevacizumab. Conclusion Increased LSF is an independent prognostic indicator of worse survival in patients undergoing radioembolization for liver-dominant metastatic colorectal adenocarcinoma. High LSF correlates poorly to other potential markers of tumor size, such as tumor-to-liver volume ratio or serum carcinoembryonic antigen level, and does not correlate to the presence of extrahepatic metastases. © RSNA, 2016 Online supplemental material is available for this article.

Purpose: SIRFLOX was a randomized, multicenter trial designed to assess the efficacy and safety of adding selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy in patients with previously untreated metastatic colorectal cancer., Patients and Methods: Chemotherapy-naïve patients with liver metastases plus or minus limited extrahepatic metastases were randomly assigned to receive either modified FOLFOX (mFOLFOX6; control) or mFOLFOX6 plus SIRT (SIRT) plus or minus bevacizumab. The primary end point was progression-free survival (PFS) at any site as assessed by independent centralized radiology review blinded to study arm., Results: Between October 2006 and April 2013, 530 patients were randomly assigned to treatment (control, 263; SIRT, 267). Median PFS at any site was 10.2 v 10.7 months in control versus SIRT (hazard ratio, 0.93; 95% CI, 0.77 to 1.12; P = .43). Median PFS in the liver by competing risk analysis was 12.6 v 20.5 months in control versus SIRT (hazard ratio, 0.69; 95% CI, 0.55 to 0.90; P = .002). Objective response rates (ORRs) at any site were similar (68.1% v 76.4% in control v SIRT; P = .113). ORR in the liver was improved with the addition of SIRT (68.8% v 78.7% in control v SIRT; P = .042). Grade ≥ 3 adverse events, including recognized SIRT-related effects, were reported in 73.4% and 85.4% of patients in control versus SIRT., Conclusion: The addition of SIRT to FOLFOX-based first-line chemotherapy in patients with liver-dominant or liver-only metastatic colorectal cancer did not improve PFS at any site but significantly delayed disease progression in the liver. The safety profile was as expected and was consistent with previous studies., (© 2016 by American Society of Clinical Oncology.)

Background: In colorectal cancer (CRC), unresectable liver metastases are linked to poor prognosis. Systemic chemotherapy with regimens such as FOLFOX (combination of infusional 5-fluorouracil, leucovorin and oxaliplatin) is the standard first-line treatment. The SIRFLOX trial was designed to assess the efficacy and safety of combining FOLFOX-based chemotherapy with Selective Internal Radiation Therapy (SIRT or radioembolisation) using yttrium-90 resin microspheres (SIR-SpheresR; Sirtex Medical Limited, North Sydney, Australia)., Methods/design: SIRFLOX is a randomised, multicentre trial of mFOLFOX6 chemotherapy+/-SIRT as first-line treatment of patients with liver-only or liver-predominant metastatic CRC (mCRC). The trial aims to recruit adult chemotherapy-naive patients with proven liver metastases with or without limited extra-hepatic disease, a life expectancy of >=3 months and a WHO performance status of 0-1. Patients will be randomised to receive either mFOLFOX6 or SIRT+mFOLFOX6 (with a reduced dose of oxaliplatin in cycles 1-3 following SIRT). Patients in both arms can receive bevacizumab at investigator discretion. Protocol chemotherapy will continue until there is unacceptable toxicity, evidence of tumour progression, complete surgical resection or ablation of cancerous lesions, or the patient requests an end to treatment. The primary endpoint of the SIRFLOX trial is progression-free survival (PFS). Secondary endpoints include: PFS in the liver; tumour response rate (liver and any site); site of tumour progression; health-related quality of life; toxicity and safety; liver resection rate; and overall survival. Assuming an increase in the median PFS from 9.4 months to 12.5 months with the addition of SIRT to mFOLFOX6, recruiting >=450 patients will be sufficient for 80% power and 95% confidence., Discussion: The SIRFLOX trial will establish the potential role of SIRT+standard systemic chemotherapy in the first-line management of mCRC with non-resectable liver metastases., Trial Registration: SIRFLOX ClinicalTrials.gov identifier: NCT00724503. Registered 25 July 2008.

Unlabelled: In patients with liver malignancies potentially amenable to curative extended right hepatectomy but insufficient size of the future liver remnant (FLR), portal vein embolization (PVE) of the tumor-bearing liver is used to induce contralateral liver hypertrophy but leaves the tumor untreated. Radioembolization (RE) treats the tumor in the embolized lobe along with contralateral hypertrophy induction. We performed a matched-pair analysis to compare the capacity for hypertrophy induction of these two modalities. Patients with right-hepatic secondary liver malignancies with no or negligible left-hepatic tumor involvement who were treated by right-lobar PVE (n = 141) or RE (n = 35) at two centers were matched for criteria known to influence liver regeneration following PVE: 1) baseline FLR/Total liver volume ratio (<25 versus ≥ 25%); 2) prior platinum-containing systemic chemotherapy; 3) embolization of segments 5-8 versus 4-8; and 4) baseline platelet count (<200 versus ≥ 200 Gpt/L).The primary endpoint was relative change in FLR volume from baseline to follow-up. Twenty-six matched pairs were identified. FLR volume increase from baseline to follow-up (median 33 [24-56] days after PVE or 46 [27-79] days after RE) was significant in both groups but PVE produced significantly more FLR hypertrophy than RE (61.5 versus 29%, P < 0.001). Time between treatment and follow-up was not correlated with the degree of contralateral hypertrophy achieved in both groups. Although group differences in patient history and treatment setting were present and some bias cannot be excluded, this was minimized by the matched-pair design, as remaining group differences after matching were found to have no significant influence on contralateral hypertrophy development., Conclusion: PVE induces significantly more contralateral hypertrophy than RE with therapeutic (nonlobectomy) doses. However, contralateral hypertrophy induced by RE is substantial and RE minimizes the risk of tumor progression in the treated lobe, possibly making it a suitable modality for selected patients., (© 2014 by the American Association for the Study of Liver Diseases.)

Unlabelled: A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium-90-labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole-liver (45.2%) or right-lobe (38.5%) infusions. Typically, patients were Child-Pugh class A (82.5%), had underlying cirrhosis (78.5%), and had good Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1; 87.7%), but many had multinodular disease (75.9%) invading both lobes (53.1%) and/or portal vein occlusion (13.5% branch; 9.8% main). Over half had advanced Barcelona Clinic Liver Cancer (BCLC) staging (BCLC C, 56.3%) and one-quarter had intermediate staging (BCLC B, 26.8%). The median overall survival was 12.8 months (95% confidence interval, 10.9-15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6-38.1 months]; BCLC B, 16.9 months [95% CI, 12.8-22.8 months]; BCLC C, 10.0 months [95% CI, 7.7-10.9 months]). Consistent with this finding , survival varied significantly by ECOG status, hepatic function (Child-Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha-fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All-cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively., Conclusion: This analysis provides robust evidence of the survival achieved with radioembolization, including those with advanced disease and few treatment options., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Purpose: The purpose of this phase II study was to determine the safety and efficacy of TheraSphere treatment (90Y microspheres) in patients with liver-dominant colorectal metastases in whom standard therapies had failed or were judged to be inappropriate., Materials and Methods: Twenty-seven patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 135-150 Gy. Safety and toxicity were assessed according to the National Cancer Institute's Common Toxicity Criteria, version 3.0. Response was assessed with use of computed tomography (CT) and was correlated with response on [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Survival from first treatment was estimated with use of the Kaplan-Meier method., Results: Tumor response measured by FDG PET imaging exceeded that measured by CT imaging for the first (88% vs 35%) and second (73% vs 36%) treated lobes. Tumor replacement of 25% or less (vs >25%) was associated with a statistically significant increase in median survival (339 days vs 162 days; P = .002). Treatment-related toxicities included mild fatigue (n = 13; 48%), nausea (n = 4; 15%), and vague abdominal pain (n = 5; 19%). There was one case of radiation-induced gastritis from inadvertent deposition of microspheres to the gastrointestinal tract (n = 1; 4%). Three patients (11%) experienced ascites/pleural effusion after treatment with TheraSphere as a consequence of liver failure in advanced-stage metastatic disease. With the exception of these three patients whose sequelae were not considered to be related to treatment, all observed toxicities were transient and resolved without medical intervention., Conclusion: TheraSphere administration appears to provide stabilization of liver disease with minimal toxicity in patients in whom standard systemic chemotherapy regimens have failed.

Purpose: Intraarterial injection of yttrium 90 microspheres (TheraSpheres) is used in the treatment of hepatocellular carcinoma (HCC). This article presents an analysis of the incidence of liver toxicities (liver-related events) and pretreatment factors associated with liver toxicities after TheraSphere treatment., Patients and Methods: Eighty-eight TheraSphere-treated patients with low 90-day mortality risk were selected for analysis, with liver toxicities coded with use of standard oncology criteria. Descriptive and inferential statistical methods were applied to estimate the incidence of liver toxicities and to evaluate the influence of liver radiation dose and various pretreatment factors on the risk of their occurrence., Results: Sixty-eight liver toxicities occurred in 37 of the 88 patients (42%). Thirty-two patients (36%) experienced 50 liver toxicities after the first treatment and nine of 23 patients (39%) who received a second treatment experienced 18 liver toxicities. Pretreatment total bilirubin and liver radiation dose were found to be associated with the risk of at least one liver toxicity and with the time to first occurrence of a liver toxicity after first treatment. Pretreatment total bilirubin also was associated with liver toxicities after the second treatment. Most of the toxicities resolved; however, those that did not resolve were attributed to tumor progression or advancing cirrhosis., Conclusions: The risk of liver toxicities in patients with unresectable HCC treated with TheraSpheres increases with increasing pretreatment total bilirubin level and liver radiation dose to a maximum of 150 Gy for a single administration. The toxicities attributed to treatment resolved over time, and none of the patients studied had confirmed radiation-induced liver disease. Consequently, doses as high as 150 Gy on a single administration and as high as 268 Gy on repeated administrations were well tolerated.

Purpose: To present the findings of a risk-stratification survival analysis with use of data collected on a heterogeneous group of patients with hepatocellular carcinoma (HCC) treated with TheraSphere., Materials and Methods: Baseline, treatment, and follow-up data were collected and analyzed from 121 TheraSphere-treated patients. Survival analyses were performed to identify those variables most strongly associated with 3-month mortality. The presence of any of the identified risk variables resulted in the assignment of a patient to the high-risk category., Results: Five liver reserve and two non-liver reserve variables were identified and used to stratify patients into low- or high-risk groups. Sixteen of the 33 patients assigned to the high-risk group (49%) did not survive the first 3 months after treatment, compared with six of the 88 patients assigned to the low-risk group (7%; Fisher exact test, P < .0001). Median survival for the low- and high-risk groups were 466 days and 108 days, respectively (hazard ratio, 6.0; P < .0001). Eleven of 12 patients who experienced a treatment-related major complication ending in death were included in the high-risk group. No single variable explained the major complication relationship to treatment., Conclusion: Patients with HCC who are being considered for treatment with TheraSpheres should be evaluated for the presence of the risk variables described herein. The absence of these variables is predictive of improved survival (median of 466 days) compared with patients at high risk (median of 108 days).

The 1990s have seen major changes in the health care delivery system. One of the more useful ones has been the CareMap, an interdisciplinary tool for managing, evaluating and improving patient care. The article discusses the use of a diabetic ketoacidosis CareMap in the medical intensive care unit in a large community hospital. The impact of the CareMap on cost containment and use of resources is also addressed. Although the CareMap represents only one of the many changes that have evolved in the past several years, it is certain to have a critical effect on patient care quality because it combines a variety of disciplines and identifies problem issues that encourage a collaborative approach to patient care.