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Introduction: The United States is in the midst of an opioid overdose epidemic. Emerging evidence suggests that medical cannabis (MC) may reduce use of opioids for pain in some individuals, with potential impacts on opioid-related overdose. However, there may be other important differences between states that did, and did not, adopt MC., Methods: This study evaluated differences following legal MC sales on US opioid-related overdose deaths, corrected for population, from 1999 to 2017 using an interrupted time series. Comparisons by MC status were also made for Medicaid expansion and the Centers for Disease Control death certificate reporting quality (0: 2 [1]=19.03, p<0.0005). MC states (1.50±0.23) had higher death certificate reporting quality relative to states without MC (0.78±0.22, p < 0.05)., Discussion: MC states had higher rates of opioid overdoses. Although there was no decrease in association with MC introduction, these results were confounded by states without MC having lower overdose reporting quality. Medicaid expansion was also more common in states with MC. Finally, the potency of fentanyl analogues may have obscured any protective effects of MC against illicit opioid harms., Competing Interests: BJP has received research support from the medical marijuana dispensaries and travel from cannabis advocacy non-profit organizations (e.g. Patients Out of Time). He is part of an osteoarthritis research team supported by Pfizer and Eli Lilly. The other authors have no disclosures., (Thieme. All rights reserved.)

Introduction and Objectives: The coronavirus disease 2019 (COVID-19) pandemic has been a challenge globally. In severe acute respiratory syndrome (SARS) epidemic 60% of patients had hepatic injury, due to phylogenetic similarities of the viruses it is assumed that COVID-19 is associated with acute liver injury. In this meta-analysis, we aim to study the occurrence and association of liver injury, comorbid liver disease and elevated liver enzymes in COVID-19 confirmed hospitalizations with outcomes., Materials and Methods: Data from observational studies describing comorbid chronic liver disease, acute liver injury, elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and outcomes of COVID-19 hospitalized patients from December 1, 2019, to June 30, 2020 was extracted following PRISMA guidelines. Adverse outcomes were defined as admission to intensive care unit (ICU), oxygen saturation <90%, invasive mechanical ventilation (IMV), severe disease and in-hospital mortality. Odds ratio (OR) and 95% confidence interval (95% CI) were obtained., Results: 24 studies with 12,882 confirmed COVID-19 patients were included. Overall prevalence of CM-CLD was 2.6%, COVID-19-ALI was 26.5%, elevated AST was 41.1% and elevated ALT was 29.1%. CM-CLD had no significant association with poor outcomes (pooled OR: 0.96; 95% CI: 0.71-1.29; p=0.78). COVID-19-ALI (1.68;1.04-2.70; p=0.03), elevated AST (2.98; 2.35-3.77; p<0.00001) and elevated ALT (1.85;1.49-2.29; p<0.00001) were significantly associated with higher odds of poor outcomes., Conclusion: Our meta-analysis suggests that acute liver injury and elevated liver enzymes were significantly associated with COVID-19 severity. Future studies should evaluate changing levels of biomarkers amongst liver disease patients to predict poor outcomes of COVID-19 and causes of liver injury during COVID-19 infection., (Copyright © 2020 AEDV. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Gastroparesis (GP), meaning "gastric palsy", is a chronic medical condition characterized by delayed or absent gastric emptying in the absence of mechanical obstruction. The primary objective of this study was to determine the patient-specific outcomes and the burden of GP on the US healthcare system., Methods: This was a population-based, retrospective study designed to analyze data available from the Nationwide Inpatient Sample (NIS) for 2016 and 2017. Using the International Classification of Diseases, Tenth Revision (ICD-10) codes, we identified adult (18 years or older) hospitalizations with a principal diagnosis of GP. The study sample was further classified into two distinct groups based on the presence or absence of GP, namely diabetic GP (DGP) and non-diabetic GP (NDGP). The primary outcome of our study was inpatient mortality secondary to GP while the secondary outcomes included the odds of system-based complications and the burden of the disease on the United States healthcare system., Results: We identified 99,695 adult (≥ 18 years) hospitalizations with a principal discharge diagnosis of GP in 2016 and 2017. Of these patients, 78.1% (77,885) had DGP and 21.9% (21,810) were classified in the NDGP group. We noted a higher proportion of women (79.3% vs. 63.4%, P < 0.001), patients with a history of smoking (35.8% vs. 31.7%, P < 0.001) and chronic obstructive pulmonary disease (10.7% vs. 7.6%, P < 0.001) in the NDGP group. After adjusting for common confounders excluding age, the inpatient mortality for GP was found to be 0.25%. Furthermore, after adjustments were made for the Charlson comorbidity index (CCI), we noted higher odds of mortality in the NDGP group (0.30% vs. 0.23%, adjusted odds ratio (aOR): 3.18, 95% confidence interval (CI): 1.75 - 5.79, P < 0.001) compared to the DGP group. Additionally, patients with NDGP had a higher mean length of stay (5 vs. 4.1 days, P < 0.001) and higher mean total hospital charge ($44,100 vs. $35,500, P < 0.001) compared to those with DGP. The NDGP group also had higher odds of sepsis, deep vein thrombosis (DVT) and pulmonary embolism (PE); however, the odds of developing acute kidney injury (AKI) were lower than that of the DGP group., Conclusions: The inpatient mortality for GP was found to be 0.25%. After adjusting for CCI, patients with NDGP had higher odds of inpatient mortality compared to the DGP group. Additionally, patients with NDGP were associated with a longer length of hospital stay, mean total healthcare cost and higher odds of complications such as sepsis, DVT and PE during the hospitalization., Competing Interests: The authors report no conflict of interest., (Copyright 2021, Kichloo et al.)

Neuroendocrine tumors (NETs) are a relatively rare entity; however, the incidence and prevalence of these tumors are increasing, likely attributed to improved diagnostic accuracy. The diagnosis of suspected NETs is facilitated by clinical symptoms, laboratory test abnormalities such as elevated chromogranin-A, and other diagnostic modalities such as the use of computed tomography scans, magnetic resonance imaging scans, positron emission tomography (PET) scans, and biopsy. The expression of high levels of somatostatin receptors in NETs enables the use of a specialized PET scan using the radiolabeled somatostatin analogues 68Ga-DOTATATE. The sensitivity and specificity of 68Ga-DOTATATE PET is very high for the diagnosis of NETs, but the specificity decreases especially with no clear symptoms and with only borderline elevated tumor markers. We present a case of a suspected NET, which was initially diagnosed as a metastatic NET by virtue of a positive 68Ga-DOTATATE PET scan; however, on biopsy it was revealed to be a squamous cell carcinoma originating from the head and neck.

Globally, coronavirus is causing more social, economic and healthcare disruption than expected. The emerging literature has reported the complications of coronavirus, and the mortality and risk factors involved, including cardiac injury and multisystem organ failure. In this meta-analysis, we aim to evaluate the association of elevated troponin I levels with outcomes in COVID-19 hospitalized patients. Observational studies describing troponin I levels and outcomes of COVID-19 hospitalized patients from 1 December 2019 to 15 August 2020 were identified. Data were extracted following PRISMA guidelines with a consensus of two independent reviewers. Adverse outcomes were defined as admission to intensive care units (ICUs), oxygen saturation <90%, invasive mechanical ventilation (IMV), and in-hospital mortality. The odds ratio (OR) and 95% confidence interval (95% CI) were obtained and forest plots were created using random-effects models. Ten studies with 3982 confirmed COVID-19 patients were included. In patients with poor outcomes, the prevalence of elevated troponin I levels was 51% (690/1341). In meta-analysis, patients with elevated troponin I levels had higher odds of poor outcomes compared to better outcomes with pooled OR of 7.92 (95% CI: 3.70-16.97; p<0.00001) with 70% heterogeneity (p=0.0005). Our meta-analysis suggests that COVID-19 patients with elevated troponin I levels had a higher risk of poor outcomes. Hence, evaluating the troponin I levels might be helpful in preventing risk of cardiac complications and other organ dysfunction.

Purpose: To evaluate neuro-oncology clinician time utilization for medication management and identify a cost beneficial role for integration of a dedicated pharmacy specialists., Methods: A pharmacist was temporarily integrated into a neuro-oncology clinic for a 30-day period to evaluate the clinical practice and perform a 14-day clinical chart evaluation and patient interactions as part of a single institutional exploratory analysis. The pharmacist completed screenings for drug-drug interactions, new therapies, medication reconciliation, and advanced interventions as part of a collaborative practice agreement for pharmacist autonomy. Pharmacist time spent was calculated and documented within the patient encounters to support physician decision-making. A comparative estimate of pharmacist versus physician time utilization and cost for each was completed to derive a savings analysis for integration of a dedicated clinic pharmacist., Result: During the 14-day clinical assessment, the pharmacist completed 147 encounters with 338 interventions. Of the encounters, 90% (n = 132) were higher complexity requiring plan modification, and approximately 48% (n = 162) of all interventions required ≥10 minutes of the pharmacist's time. Physician non-patient-facing time devoted to medication tasks was 5-hours weekly (0.125 FTE, full time equivalents), an estimated direct salary cost of $937/week ($45,000 yearly). Hire of a part-time pharmacist at 0.50 FTE would cover the clinical need with supported documentation and medication monitoring at a cost of $45,000/year., Conclusion: Defining the roles for dedicated neuro-oncology clinic pharmacists allows for cost-savings through re-allocation of physician time and improves subspecialty clinic operations as well as patient care.

While immuno-oncotherapy (IO) has significantly improved outcomes in the treatment of systemic cancers, various neurological complications have accompanied these therapies. Treatment with immune checkpoint inhibitors (ICIs) risks multi-organ autoimmune inflammatory responses with gastrointestinal, dermatologic, and endocrine complications being the most common types of complications. Despite some evidence that these therapies are effective to treat central nervous system (CNS) tumors, there are a significant range of related neurological side effects due to ICIs. Neuroradiologic changes associated with ICIs are commonly misdiagnosed as progression and might limit treatment or otherwise impact patient care. Here, we provide a radiologic case series review restricted to neurological complications attributed to ICIs, anti-CTLA-4, and PD-L-1/PD-1 inhibitors. We report the first case series dedicated to the review of CNS/PNS radiologic changes secondary to ICI therapy in cancer patients. We provide a brief case synopsis with neuroimaging followed by an annotated review of the literature relevant to each case. We present a series of neuroradiological findings including nonspecific parenchymal and encephalitic, hypophyseal, neural (cranial and peripheral), meningeal, cavity-associated, and cranial osseous changes seen in association with the use of ICIs. Misdiagnosis of radiologic abnormalities secondary to neurological immune-related adverse events can impact patient treatment regimens and clinical outcomes. Rapid recognition of various neuroradiologic changes associated with ICI therapy can improve patient tolerance and adherence to cancer therapies., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Paralytic ileus is a common clinical condition leading to significant morbidity and mortality. Most studies to date have focused on postoperative ileus, a common but not exclusive cause of the condition. There are limited epidemiological data regarding the incidence and impact of paralytic ileus and its relationship to other clinical conditions. In this cross-sectional study, we analyzed national inpatient hospitalization trends, demographic variation, cost of care, length of stay, and mortality for paralytic ileus hospitalizations as a whole., Methods: The National Inpatient Sample database was used to identify all hospitalizations with the diagnosis of paralytic ileus (International Classification of Diseases, 9th Revision code 560.1) as primary or secondary diagnosis during the period from 2001 to 2011. Statistical analysis was performed using Cochran-Armitage trend test, Wilcoxon rank sum test, and Poisson regression., Results: In 2001, there were 362,561 hospitalizations with the diagnosis of paralytic ileus as compared to 470,110 in 2011 (p < 0.0001). The age group 65-79 years was most commonly affected by paralytic ileus throughout the study period. In-hospital all-cause mortality decreased from 6.03% in 2001 to 5.10% in 2011 (p < 0.0001). However, the average cost of care per hospitalization increased from US$19,739 in 2001 to US$26,198 in 2011 (adjusted for inflation, p < 0.0001)., Conclusion: There was a significant rise in the number of hospitalizations of paralytic ileus with increased cost of care and reduced all-cause mortality., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Introduction: Cerebral sinovenous thrombosis (CSVT) represents the second most common type of venous thromboembolism (VTE) in children. Current literature includes limited evidence on risk factors for CSVT, particularly in the pediatric population. We sought to determine risk factors for CSVT in pediatric patients through a single-institutional case-control study. In addition, we evaluated thrombophilias, treatments and outcomes in CSVT among cases., Methods: A case-control study was performed at Johns Hopkins All Children's Hospital on patients admitted from March 31, 2006 through April 1, 2018. Cases were identified using diagnostic codes and confirmed based on electronic health record (EHR) and neuroimaging review. Controls were matched in a 2:1 fashion accounting for the month and year of admission., Results: A total of 60 CSVT cases and 120 controls were identified. Median (range) age was 4.8 years (0-21.3 years) for cases and 5.6 years (0-20.0 years) for controls. Factors putatively associated with CSVT in unadjusted analyses were: corticosteroid use, presence of a central venous catheter, mechanical ventilation, systemic infection, head/neck infection, head/neck trauma, and chronic inflammatory disease. In the multivariable model, head/neck infection (OR: 13.8, 95% CI: 4.87-38.7; P < 0.01), head/neck trauma (OR: 12.7, 95% CI: 2.88-56.2; P < 0.01), and mechanical ventilation (OR: 9.32, 95% CI: 2.35-36.9; P = 0.01) remained independent, statistically-significant risk factors. 61% of patients were subacutely treated with anticoagulants and of those, only two developed relevant bleeding after initiation of therapy., Conclusions: This single-institutional case-control study reveals that head/neck infection, head/neck trauma, and mechanical ventilation are independent risk factors for pediatric CSVT. These findings will be further investigated via a cooperative registry of pediatric hospital-acquired VTE, by which a risk model for pediatric CSVT will be developed and validated, in order to inform future preventive strategies in at-risk pediatric patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Pathogenic variants (PVs) in multiple genes are known to increase the risk of early-onset renal cancer (eoRC). However, many eoRC patients lack PVs in RC-specific genes; thus, their genetic risk remains undefined. Here, we determine if PVs in DNA damage response and repair (DDRR) genes are enriched in eoRC patients undergoing cancer risk assessment. Retrospective review of de-identified results from 844 eoRC patients, undergoing testing with a multi-gene panel, for a variety of indications, by Ambry Genetics. PVs in cancer-risk genes were identified in 12.8% of patients-with 3.7% in RC-specific, and 8.55% in DDRR genes. DDRR gene PVs were most commonly identified in CHEK2, BRCA1, BRCA2, and ATM. Among the 2.1% of patients with a BRCA1 or BRCA2 PV, < 50% reported a personal history of hereditary breast or ovarian-associated cancer. No association between age of RC diagnosis and prevalence of PVs in RC-specific or DDRR genes was observed. Additionally, 57.9% patients reported at least one additional cancer; breast cancer being the most common (40.1% of females, 2.5% of males). Multi-gene testing including DDRR genes may provide a more comprehensive risk assessment in eoRC patients. Further validation is needed to characterize the association with eoRC.

Introduction: A common criticism of the peer-review process is the often disparate nature of reviewer recommendations when a decision is rendered which belies the supposed uniformity of the process. The purpose of this investigation was to examine level of agreement between reviewers for Foot & Ankle International (FAI) and analyze variables which may have influenced agreement in order to better understand the peer-review process., Methods: Approval to conduct this investigation was obtained from the Executive Board and Editor in Chief of FAI. All manuscripts submitted to FAI during the calendar year 2016 which underwent formal peer-review were included in the analysis. For each reviewed manuscript, demographic data was collected regarding specific reviewer and manuscript characteristics in a de-identified manner., Results: 442 manuscripts underwent formal blinded peer-review by two independent reviewers during the study period. Only 199 manuscripts (45%) had a decision rendered in which both reviewers agreed on the same initial recommendation. There were no differences in demographic characteristics between the group of reviewers who agreed as compared to those who disagreed on the initial round of peer review. A similar number of indexed peer-reviewed publications between reviewers correlated with increased levels of agreement., Conclusions: During the study period, there was 45% initial agreement between reviewers for FAI when assessing the same manuscript. Aside from research productivity, no other reviewer-specific variables examined in this investigation were found to correlate with agreement. Specific recommendations and changes may be considered to increase the efficiency and effectiveness of the peer-review process., (Copyright © 2019 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Background: The Joint Commission lists improving staff communication (handoffs) as part of several National Safety Goals. In this study, we developed an electronic web-based charting system for clinical pathology handoffs, which primarily consist of transfusion medicine calls, and evaluated the advantages over a paper-based handwritten call log., Materials and Methods: A secure online web browser application using Research Electronic Data Capture (REDCap) was designed to document on-call pathology resident consults. A year after implementation, an online survey was administered to our pathology residents in order to evaluate and compare the usability of the electronic application (e-consults) to the previous handwritten call log, which was a notebook where trainees hand wrote different components of the consult., Results: The REDCap web-based application includes discrete fields for patients' information, requesting physician contact, type of consult, action items for follow-up and faculty responses, as well as other information. These components have eventually progressed to be an online consult call catalog. With approximately 1079 consults per year, transfusion medicine-related calls account for ~90% of the encounters, while clinical chemistry, microbiology and immunology calls constitute the remainder. The overall response rate of the survey was 96% (29 of 30 participants). Of the 16 respondents who experienced both call log systems, 100% responded that REDCap was an improvement over the handwritten call log (P < 0·0001)., Conclusion: E-consult documentation entered into a web-based application was a user-friendly, secure clinical information access and effective handoff system as compared to a paper-based handwritten call log., (© 2020 International Society of Blood Transfusion.)

Background: There is an immediate need for research on the mechanism underlying telomerase activation and overexpression., Materials & Methods: A total of 174 patients with lung cancer ( n  = 106) and benign lung disease ( n  = 68) were recruited for the current study. The mRNA expression levels of E6, E7, LKB1, Sp1, and hTERC in brushing cells were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and hTERC amplification was also detected by fluorescence in situ hybridization (FISH). To investigate the potential mechanism, bidirectional genetic manipulation was performed in well-established lung cancer cell lines., Results: Our results indicated that the mRNA expression levels of E6, E7, Sp1, and hTERC and the amplification level of hTERC were significantly increased in the malignant group compared with those of the benign group ( p  < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group ( p  < 0.01). The correlation between E6, E7, Sp1, and hTERC expression was positive but was negative with LKB1 ( p  < 0.01). Our results also showed that HPV16 E6/E7 downregulated the expression of LKB1 at both the protein and mRNA levels. The loss of LKB1 upregulated Sp1 expression, and also promoted Sp1 activity. Sp1 further upregulated hTERC at the mRNA and gene amplification levels. Thus, we proposed a HPV-LKB1-Sp1-hTERC axis of E6/E7 upregulation of hTERC expression., Conclusion: We demonstrated for the first time that E6 and E7 promoted hTERC mRNA expression and the amplification of hTERC by relieving the effect of LKB1 on the phosphorylation of Sp1. Sp1 further activated hTERC by directly binding to the promoter regions of hTERC., Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Many patients have reported that they decrease their use of opioids after starting medical cannabis (MC) but less is known for alcohol. The objective of this exploratory study was to identify any factors which differentiate alcohol abaters from those that do not modify their alcohol use after starting MC (non-abaters). Comparisons were made to identify any demographic, dosing, or health history characteristics which differentiated alcohol abaters (N = 47) from non-abaters (N = 65). Respondents selected from among a list of 37 diseases/health conditions (e.g. diabetes, sleep disorders). Abaters and non-abaters were indistinguishable in terms of sex, age, or prior drug history. A greater percentage of abaters (59.6%) than non-abaters (40.6%, p < .05) reported using MC two or more times per day. Abaters were more likely to be employed (68.1%) than non-abaters (51.1%, p < .05). Abaters also reported having significantly more health conditions and diseases (3.3 ± 2.0) than non-abaters (2.4 ± 1.4, p < .05). This small study offers some insights into the profile of patients whose self-reported alcohol intake decreased following initiation of MC. Additional prospective or controlled research into the alcohol abatement phenomenon following MC may be warranted.

Background: Dent disease type 1 (DD1) is a rare X-linked disorder caused mainly by CLCN5 mutations. Patients may present with nephrotic-range proteinuria leading to erroneous diagnosis of focal segmental glomerulosclerosis (FSGS) and unnecessary immunosuppressive treatments., Methods: The following cohorts were screened for CLCN5 mutations: Chronic Kidney Disease in Children (CKiD; n = 112); Multicenter FSGS-Clinical Trial (FSGS-CT) (n = 96), and Novel Therapies for Resistant FSGS Trial (FONT) (n = 30). Urinary α 1 -microglobulin (α 1 M), albumin (A), total protein (TP), and creatinine (Cr) were assessed from CKiD subjects (n = 104); DD1 patients (n = 14); and DD1 carriers (DC; n = 8). TP/Cr, α 1 M/Cr, α 1 M/TP, and A/TP from the CKiD cohort were compared with DD1 and DC., Results: No CLCN5 mutations were detected. TP/Cr was lower in DC and CKiD with tubulointerstitial disease than in DD1 and CKiD with glomerular disease (p < 0.002). α 1 M/Cr was higher in DD1 than in CKiD and DC (p < 0.001). A/TP was lower in DD1, DC, and CKiD with tubulointerstitial disease and higher in CKiD with glomerular disease (p < 0.001). Thresholds for A/TP of ≤ 0.21 and α 1 M/Cr of ≥ 120 mg/g (> 13.6 mg/mmol) creatinine were good screens for Dent disease., Conclusions: CLCN5 mutations were not seen in screened CKiD/FSGS cohorts. In our study, a cutoff of TP/Cr > 600 mg/g (> 68 mg/mmol) and A/TP of < 0.3 had a high sensitivity and specificity to distinguish DD1 from both CKiD glomerular and tubulointerstitial cohorts. α 1 M/Cr ≥ 120 mg/g (> 13.6 mg/mmol) had the highest sensitivity and specificity when differentiating DD1 and studied CKiD populations.

Thrombotic complications of the novel coronavirus (COVID-19) are a concerning aspect of the disease, due to the high incidence in critically ill patients and poor clinical outcomes. COVID-19 predisposes patients to a hypercoagulable state, however, the pathophysiology behind the thrombotic complications seen in this disease is not well understood. Several mechanisms have been proposed and the pathogenesis likely involves a host immune response contributing to vascular endothelial cell injury, inflammation, activation of the coagulation cascade via tissue factor expression, and shutdown of fibrinolysis. Treatments targeting these pathways may need to be considered to improve clinical outcomes and decrease overall mortality due to thrombotic complications. In this review, we will discuss the proposed pathophysiologic mechanisms for thrombotic complications in COVID-19, as well as treatment strategies for these complications based on the current literature available.

Tumor immune escape is now a hallmark of cancer development, and therapies targeting these pathways have emerged as standard of care. Specifically, immune checkpoint signal blockade offers durable responses and increased overall survival. However, the majority of cancer patients still do not respond to checkpoint blockade immune therapy leading to an unmet need in tumor immunology research. Sex-based differences have been noted in the use of cancer immunotherapy suggesting that sex hormones such as estrogen may play an important role in tumor immune regulation. Estrogen signaling already has a known role in autoimmunity, and the estrogen receptor can be expressed across multiple immune cell populations and effect their regulation. While it has been well established that tumor cells such as ovarian carcinoma, breast carcinoma, and even lung carcinoma can be regulated by estrogen, research into the role of estrogen in the regulation of tumor-associated immune cells is still emerging. In this chapter, we discuss the role of estrogen in the tumor immune microenvironment and the possible immunotherapeutic implications of targeting estrogen in cancer patients.

In this article, we present a case of a young female patient with previously diagnosed lupus pneumonitis, now with a flare and new superimposed COVID-19 infection that was treated with intravenous steroids. On computed tomography scans, she had extensive interstitial lung fibrosis in addition to a positive COVID-19 polymerase chain reaction test requiring 6 L of oxygen via nasal cannula on admission. After administration of methylprednisolone, the patient improved and was weaned off her oxygen requirements and was discharged home.

Lung cancer remains the leading cause of cancer-related deaths worldwide. In order to understand lung cancer biology and evaluate novel therapeutic strategies, preclinical mouse models have been developed that mimic early and advanced-stage lung cancer. Among autochthonous models, carcinogen-induced systems are valuable preclinical tools since tobacco smoking remains the number one risk factor for lung tumor development. Among the several thousand chemicals within cigarette smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen with tumorigenic effects described in both mice and humans. Herein, we describe the methodology for inducing lung tumors in mice using the tobacco carcinogen NNK and subsequent lung fixation for quantitative assessment of tumor development and analysis of oncogenic mutations in tumors.

A 64-year old male presented to the hospital with a 1-week history of stools with bright red blood. Subsequent colonoscopy with a biopsy revealed a low-lying, moderately differentiated, rectal adenocarcinoma. A pelvic magnetic resonance imaging done afterwards showed a possible T3N1 rectal cancer with intact muscularis mucosa and a singular presacral lymph node enlargement. Furthermore, a suspicious peripheral prostatic enlargement and a possible left iliac crest sclerotic bone lesion were incidentally identified. 18 F-FDG (fluorodeoxyglucose) PET (positron emission tomography) scan confirmed a primary FDG avid rectal tumor and a presacral lymph node; however, there was no prostate or iliac crest uptake. A serum prostate-specific antigen performed in the hospital returned with a value of 37 ng/mL, which prompted a prostate biopsy, eventually returning as positive for adenocarcinoma. Consequently, a 68 Ga-PSMA PET scan to rule out possible metastatic prostate disease revealed increased PSMA expression in the prostate only. After consultation with the radiologist and nuclear medicine physician who concluded the iliac crest lesion is likely not cancerous, the final diagnosis of T3N1 rectal cancer with simultaneous high-grade prostate adenocarcinoma was declared. This case highlights the low sensitivity of 18 F-FDG PET scans for prostate cancer, the need for routine serum prostate-specific antigen screening, and the progression of 68 Ga-PSMA PET as a diagnostic tool for prostate cancer.

The literature about the association between Chiari malformations (CMs) and scoliosis has been growing over the last three decades; yet, no consensus on the optimal management approach in this patient population has been reached. Spinal anomalies such as isolated syrinxes, isolated CM, and CM with a syrinx are relatively common among patients with presumed idiopathic scoliosis (IS), a rule that also applies to scoliosis among CM patients as well. In CM patients, scoliosis presents with atypical features such as early onset, left apical or kyphotic curvature, and neurological deficits. While spinal X-rays are essential to confirm the diagnosis of scoliosis among CM patients, a magnetic resonance imaging (MRI) is also recommended in IS patients with atypical presentations. Hypotheses attempting to explain the occurrence of scoliosis in CM patients include cerebellar tonsillar compression of the cervicomedullary junction and uneven expansion of a syrinx in the horizontal plane of the spinal cord. Early detection of scoliosis on routine spinal examination and close follow-up on curve stability and progression are essential initial steps in the management of scoliosis, especially in patients with CM, who may require full spine MRI to screen for associated neuro-axial anomalies; bracing and spinal fusion may be subsequently pursued in high-risk patients.

In the last few years, immunotherapy has transformed the way we treat solid tumors, including melanoma, lung, head neck, breast, renal, and bladder cancers. Durable responses and long-term survival benefit has been experienced by many cancer patients, with favorable toxicity profiles of immunotherapeutic agents relative to chemotherapy. Cures have become possible in some patients with metastatic disease. Additional approvals of immunotherapy drugs and in combination with other agents are anticipated in the near future. Multiple additional immunotherapy drugs are in earlier stages of clinical development, and their testing in additional tumor types is under way. Despite considerable early success and relatively fewer side effects, the majority of cancer patients do not respond to checkpoint inhibitors. Additionally, while the drugs are generally well tolerated, there is still the potential for significant, unpredictable and even fatal toxicity with these agents. Improved biomarkers may help to better select patients who are more likely to respond to these drugs. Two key biologically important predictive tissue biomarkers, specifically, PD-L1 and mismatch repair deficiency, have been FDA-approved in conjunction with the checkpoint inhibitor, pembrolizumab. Tumor mutation burden, another promising biomarker, is emerging in several tumor types, and may also soon receive approval. Finally, several other tissue and liquid biomarkers are emerging that could help guide single-agent immunotherapy and in combination with other agents. Of these, one promising investigational biomarker is alteration or deficiency in DNA damage response (DDR) pathways, with altered DDR observed in a broad spectrum of tumors. Here, we provide a critical overview of current, emerging, and investigational biomarkers in the context of response to immunotherapy in solid tumors.

Background: Robotic-assisted percutaneous coronary intervention (R-PCI) has been successfully employed in the United States since 2011. Performing R-PCI from a remote location has never been reported but if feasible would extend availability of treatment to many patients with coronary artery disease (CAD) who would otherwise go without., Objective: To assess the feasibility of remote tele-R-PCI with the operator 20 miles away from the patients., Methods: Five patients with single, type A coronary artery lesions treatable by PCI consented to participate. The primary endpoint was procedural success with no major adverse cardiac events (MACE) before discharge. Procedural success was defined as achieving < 10% diametric stenosis of the occluded target vessel utilizing tele-R-PCI balloon angioplasty and stent deployment (CorPath GRX®, Corindus Vascular Robotics, USA) without converting to in-lab manual PCI by an on-site standby team. Procedural, angiographic, and safety data were collected as were questionnaire scores from the remote operator evaluating the robot-network composite, image clarity, and overall confidence in the procedure., Results: The primary endpoint was achieved in 100% of patients. No procedural complications or adverse events occurred, and all patients were discharged the following day without MACE. The operator scores were favorable with the operators rating the procedure as equivalent to an in-lab procedure., Conclusions: Performing long distance tele-R-PCI in patients with CAD is feasible with predictably successful outcomes if reliable network connectivity and local cardiac catheterization facilities are available., (© 2019 Published by Elsevier Ltd.)

Introduction: Over the recent years, there has been increased interest in the use of transradial (TR) access for percutaneous coronary intervention (PCI), including rotational atherectomy (RA). However, a large proportion of operators seem to be reluctant to use TR access for complex PCI including rotational atherectomy for heavily calcified coronary lesions., Methods: We searched MEDLINE, ClinicalTrials.gov and the Cochrane Library for studies comparing radial versus femoral access in patients undergoing RA. Studies were included if they reported at least one of the following outcomes in each group separately: major adverse cardiac events (MACE), major bleeding, stent thrombosis, myocardial infarction (MI), hospital length of stay, radiation exposure, procedure time, procedure success and all-cause mortality. Odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) were calculated and a p-value of <0.05 was considered as a level of significance., Results: This meta-analysis included 5 retrospective studies with 3315 patients undergoing RA via radial access and 5838 patients via femoral access. Radial access was associated with lower major access site bleeding (OR: 0.45, 95% CI: 0.31-0.67, p < 0.001), and radiation exposure (MD: -16.1, 95%CI: -25.4--6.7 Gy cm 2 , p = 0.0007). There were no significant differences observed in all-cause in-hospital mortality (OR: 0.92, 95% CI: 0.69-1.23, p = 0.58); MACE (OR: 0.80, CI: 0.63, 1.02, p = 0.08), stent thrombosis (OR: 0.28, 95%CI: 0.06-1.33 p = 0.11); and MI (OR: 0.43, 95%CI: 0.15-1.24, p = 0.12). There were no significant differences in hospital stay, procedure time or procedure success between the two groups (p > 0.05)., Conclusion: This meta-analysis of 9153 patients from observational studies demonstrates similar all-cause mortality, MACE, procedural success and procedural time during RA performed using TR access and TF access. However, TR access was associated with decreased access site bleeding and radiation exposure. Given the observational nature of these findings, a randomized controlled trial is warranted for further evidence., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Impulsivity and hypomania are common non-motor features in Parkinson's disease (PD). The aim of this study was to find the overlapping and distinct neural correlates of these symptoms in PD. Symptoms of impulsivity and hypomania were assessed in 24 PD patients using the Barratt Impulsiveness Scale (BIS-11) and Self-Report Manic Inventory (SRMI), respectively. In addition, fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for each individual was performed. We conducted two separate multiple regression analyses for BIS-11 and SRMI scores with FDG-PET data to identify the brain regions that are associated with both impulsivity and hypomania scores, as well as those exclusive to each symptom. Then, seed-based functional connectivity analyses on healthy subjects identified the areas connected to each of the exclusive regions and the overlapping region, used as seeds. We observed a positive association between BIS-11 and SRMI scores and neural metabolism only in the prefrontal areas. Conjunction analysis revealed an overlapping region in the middle frontal gyrus. Regions exclusive to impulsivity were found in the medial part of the right superior frontal gyrus and regions exclusive to hypomania were in the right superior frontal gyrus, right precentral gyrus and right paracentral lobule. Connectivity patterns of seeds exclusively related to impulsivity were different from those for hypomania in healthy brains. These results provide evidence of both overlapping and distinct regions linked with impulsivity and hypomania scores in PD. The exclusive regions for each characteristic are connected to specific intrinsic functional networks.

Background: There is a paucity of data regarding the racial and sex disparities in the outcomes of multi-vessel percutaneous coronary interventions (MVPCI)., Methods: The National Inpatient Sample (NIS) was examined for the years 2010 to 2014 to incorporate adult MVPCI-related hospitalizations using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes. We excluded patients with the missing race or gender data from the final scrutiny. Discharge weights were used to obtain the national estimations. The principal outcomes were MVPCI-related racial and gender disparities in terms of the in-hospital mortality and complications, and diagnostic and therapeutic healthcare resource utilization. Secondary outcomes were the length of hospital stay (LOS) and hospitalization charges. We used the Chi-square test and t -test/ANOVA test to equate dichotomous and continuous variables respectively. A two-tailed P of <0.05 was considered clinically significant., Results: An estimated 769,502 MVPCI-related hospitalizations were recorded from 2010 to 2014 after excluding patients with the missing data (70,954; 8.4%). Black male and female were the youngest (62±13, 64±14 years). The highest non-elective admissions (M: 72.8%, F: 71.2%) were reported among Hispanics. Non-whites showed a higher proportion of comorbidities with lower resource utilization than whites. Hispanic males (OR 1.23) showed the highest odds of the in-hospital mortality whereas among females, Asians (OR 1.51), blacks (OR 1.35), followed by Hispanics (OR 1.22) revealed higher odds of in-hospital mortality. Odds of cardiac complications were highest amongst Asians (M: OR 1.19, F: OR 1.40). Black (6±8 days) and Hispanic (7±9 days) showed the highest length of stay among males and females respectively. Total hospitalization charges were highest among Asians. There was a greater increase in the all-cause mortality in non-whites from 2010 to 2014., Conclusions: This study determines the existence of racial disparities in resource utilization and outcomes in MVPCI. There is an instant need for interventions designed to govern these healthcare discrepancies., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Cervical liquid-based cytology plays an important role in the diagnosis of cervical squamous intraepithelial lesion (SIL). However, cytological evaluation alone has a relatively low sensitive. To overcome this problem, HPV DNA testing or HPV DNA combined with cytology has been applied. HPV DNA testing significantly improved the sensitivity, but the specificity is low, especially in cancer and high-grade SIL (HSIL) cases. The aim of this study was to evaluate the diagnostic utility of p16 overexpression in cervical cells of patients with HSIL and cancer. The expression of p16 was detected by immunostaining in liquid-based cells from cervical brushing in 278 patients which including: Cancer ( n = 13), HSIL ( n = 112), low-grade SIL (LSIL) ( n = 45), and Benign ( n = 108). The expression levels of p16 were significantly higher in the cancer and HSIL groups when compared with the LSIL and Benign groups ( P < 0.01). The accurate diagnostic rates of cancer and HSIL were significantly increased by p16 immunostaining plus cytology than that by cytology alone ( P < 0.01). The false negative or false positive of p16 immunostaining occurred with a unicellular pattern. With sensitivity of 96.0% and accuracy of 91.7%, the diagnostic performance of p16 immunostaining was much better than that of cytology alone with sensitivity of 36.0% and accuracy of 70.9% ( P < 0.01). p16 immunostaining in cervical brushing cells may not only be used as an ancillary tool to cytological diagnosis of cervical neoplasia but also help to distinguish HSIL from LSIL and the triage of transient infection.

Papillary fibroelastomas are rare benign primary cardiac tumors. They are typically found on valvular surfaces, most commonly, the aortic valve. In this article, we report a case of papillary fibroelastoma arising from the sinotubular junction of the ascending aorta, a rare and unusual site causing an embolic stroke.

Drug-induced liver injury (DILI) is a common cause of hepatotoxicity associated with prescription-based and over-the-counter exposure to medications and herbal supplements. Use of unapproved and inadequately tested herbal supplements can cause DILI. Therefore, thorough history-taking on exposure to herbal supplements must be an integral part of clinical evaluation of DILI. Kratom is an herbal supplement or remedy that has been known for its analgesic effects and has also been used for self-treatment of opiate withdrawals. A 52-year-old man was seen for evaluation of yellow discoloration of the eyes and skin. He reported taking kratom for right shoulder strain for at least a couple of months. On workup, his total bilirubin was noted to be 23.2 mg/dL, which peaked at 28.9 mg/dL. He was noted to have mild elevation of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Extensive laboratory tests were ordered and known causes of chronic liver disease ruled out. Magnetic resonance imaging of the abdomen was unremarkable without stigmata of portal hypertension or signs of chronic liver disease. He demonstrated no evidence of coagulopathy or hepatic encephalopathy during his illness. He underwent liver biopsy, which demonstrated histologic evidence of acute cholestatic hepatitis highly suspicious of DILI. He was advised to avoid kratom or other herbal supplements in future and prescribed ursodeoxycholic acid with significant improvement in his liver chemistries. Kratom is associated with significant liver enzymes derangements leading to DILI. Kratom is not approved for use in the United States and should be avoided.

Suboptimal iliofemoral artery access requiring alternative trans-catheter aortic valve replacement (TAVR) access is still encountered in 10-20% of subjects undergoing TAVR. Attempting suboptimal vascular access may result in excessive vessel injury, bleeding and even death. Reported is an innovative procedure to address suboptimal heavily calcified iliofemoral access by using Diamondback 360 peripheral orbital atherectomy (POA) to ablate heavy endoluminal vascular calcifications followed by balloon angioplasty. This approach enabled us to successfully deploy TAVR in extremely challenging iliofemoral anatomies that would otherwise be rendered prohibitive. The technical aspects of this procedure are delineated accompanied by a descriptive case of such procedure., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Increased anticholinergic activity resulting from pharmacotherapies used to treat schizophrenia is associated with poorer cognition. However the neural mechanisms underlying this effect are unknown. In this study of 39 early course schizophrenia outpatients, we demonstrate that increased serum anticholinergic activity is associated with reduced activation across the prefrontal cortex, including the dorsolateral, anterior, and medial prefrontal cortices, during two tasks of cognitive control. Lower activation in the dorsolateral and anterior prefrontal cortices mediated the association between increased anticholinergicity and poorer neurocognitive function. Such findings provide preliminary insight into how anticholinergic medications may impact cognition through reduced prefrontal cortical function in schizophrenia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Investigation of genetic susceptibility to cerebrovascular disease has been of growing interest. A systematic review of human studies assessing neurogenomic aspects of cerebrovascular disease was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Any association study exploring genetic variants located in the exome associated with one of the major cerebrovascular diseases with at least 500 subjects was eligible for inclusion. Of 6874 manuscripts identified, 35 studies met the inclusion criteria. Most studies of interest focused on ischemic stroke and cerebrovascular occlusive disease. Large cohort genetic association studies on hemorrhagic cerebrovascular disease were less common. In addition to rare, well-established monogenic conditions with significant risk for cerebrovascular disease, a number of genetic variants are also relevant to cerebrovascular pathogenesis as part of a multifactorial process. The 45 polymorphisms identified were located in genes involved in processes related to endothelial and vascular health (15 (33.4%) variants), plasma lipid metabolism (10 (22.2%) variants), inflammation (9 (20%) variants), coagulation (3 (6.7%) variants), and blood pressure modulation (2 (4.4%) variants), and other (6 (13.3%) variants). This work represents a comprehensive overview of genetic variants in the exome relevant to ischemic and hemorrhagic stroke pathophysiology.

Background: The epidemiology of multiple drug intolerance syndrome (MDIS) and multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic health record (EHR) data to describe prevalences of MDIS and MDAS and to examine associations with anxiety and depression., Methods: Patients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS/MDAS., Results: Of 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%) had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [aOR] 1.72 [1.65, 1.80]), depression (aOR 1.46 [1.41, 1.52]), and both anxiety and depression (aOR 1.97 [1.86, 2.08]) were associated with increased odds of MDIS. Depression was associated with increased odds of MDAS (aOR 1.41 [1.28, 1.56]), but there were no clear associations with anxiety (aOR 1.13 [0.99, 1.30]) nor both depression and anxiety (aOR 1.13 [0.92, 1.38])., Conclusion: While 6% of patients had MDIS, only 1% had MDAS. MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS; physiologic causes for MDAS warrant further investigation., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Right ventricular pacing is associated with pacing-induced cardiomyopathy in some patients. His Bundle Pacing (HBP) is an alternative site to pace to achieve ventricular contraction with fewer adverse hemodynamic effects. HBP has been shown to be safe and feasible in the short term. The few studies that look at long-term results of HBP are promising with regard to electrophysiological, echocardiographic, and clinical outcomes. Further randomized clinical trials are needed to fully understand the long-term effects of HBP., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Major vascular complications still occur in ~4.2% of transcatheter aortic valve replacement (TAVR) procedures. These complications are a major safety drawback of TAVR when compared to surgical aortic valve replacement (SAVR). Contemporary strategies designed to minimize and effectively treat vascular complications are of immense importance to a successful TAVR program. This review discusses strategies to optimize TAVR access and device choice along with TAVR access complication management. Iliac complications are less frequently encountered and can be managed effectively via the TAVR sheath over the TAVR wire employing ipsilateral proximal iliac balloon occlusion and endovascular repair. The more common arteriotomy site complications and access site closure failure require prophylactic or bail-out common femoral to superficial femoral artery wiring. Suggested is a novel method of ipsilateral arteriotomy site protection that is safe, simple and does not require additional resources. Ipsilateral wiring can also be done prophylactically or as a bailout in case of arteriotomy site complication., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in the modern world. For individuals affected by obesity-related T2DM, clinical studies have shown that carbohydrate restriction and weight loss can improve hyperglycemia, obesity, and T2DM., Areas Covered: Reducing carbohydrate intake to a certain level, typically below 50 g per day, leads to increased ketogenesis in order to provide fuel for the body. Such low-carbohydrate, ketogenic diets were employed to treat obesity and diabetes in the 19 th and early 20 th centuries. Recent clinical research has reinvigorated the use of the ketogenic diet for individuals with obesity and diabetes. Although characterized by chronic hyperglycemia, the underlying cause of T2DM is hyperinsulinemia and insulin resistance, typically as a result of increased energy intake leading to obesity. The ketogenic diet substantially reduces the glycemic response that results from dietary carbohydrate as well as improves the underlying insulin resistance. This review combines a literature search of the published science and practical guidance based on clinical experience., Expert Commentary: While the current treatment of T2DM emphasizes drug treatment and a higher carbohydrate diet, the ketogenic diet is an effective alternative that relies less on medication, and may even be a preferable option when medications are not available.

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD) which has been implicated in matochondrial (Mt) function impairment. In this study, we characterized Hcy metabolism in mouse tissues by using LC-ESI-MS/MS analysis, established tissue expression profiles for 84 nuclear-encoded Mt electron transport chain complex (nMt-ETC-Com) genes in 20 human and 19 mouse tissues by database mining, and modeled the effect of HHcy on Mt-ETC function. Hcy levels were high in mouse kidney/lung/spleen/liver (24-14 nmol/g tissue) but low in brain/heart (~5 nmol/g). S-adenosylhomocysteine (SAH) levels were high in the liver/kidney (59-33 nmol/g), moderate in lung/heart/brain (7-4 nmol/g) and low in spleen (1 nmol/g). S-adenosylmethionine (SAM) was comparable in all tissues (42-18 nmol/g). SAM/SAH ratio was as high as 25.6 in the spleen but much lower in the heart/lung/brain/kidney/liver (7-0.6). The nMt-ETC-Com genes were highly expressed in muscle/pituitary gland/heart/BM in humans and in lymph node/heart/pancreas/brain in mice. We identified 15 Hcy-suppressive nMt-ETC-Com genes whose mRNA levels were negatively correlated with tissue Hcy levels, including 11 complex-I, one complex-IV and two complex-V genes. Among the 11 Hcy-suppressive complex-I genes, 4 are complex-I core subunits. Based on the pattern of tissue expression of these genes, we classified tissues into three tiers (high/mid/low-Hcy responsive), and defined heart/eye/pancreas/brain/kidney/liver/testis/embryonic tissues as tier 1 (high-Hcy responsive) tissues in both human and mice. Furthermore, through extensive literature mining, we found that most of the Hcy-suppressive nMt-ETC-Com genes were suppressed in HHcy conditions and related with Mt complex assembly/activity impairment in human disease and experimental models. We hypothesize that HHcy inhibits Mt complex I gene expression leading to Mt dysfunction., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Patient preference is an essential component of patient-centered supportive cancer care; however, little is known about the factors that shape preference for treatment. This study sought to understand what factors may contribute to patient preference for two non-pharmacological interventions, acupuncture or cognitive behavioral therapy for insomnia (CBT-I)., Methods: We conducted individual, open-ended, semi-structured interviews among cancer survivors who had completed active treatment and met the diagnostic criteria for insomnia disorder. Two forms of codes were used for analysis: a priori set of codes derived from the key ideas and a set of codes that emerged from the data., Results: Among 53 participants, the median age was 60.7 (range 27-83), 30 participants (56.6%) were female, and 18 (34%) were non-white. We identified three themes that contributed to an individual's treatment preference: perception of the treatment's evidence base, experience with the treatment, and consideration of personal factors. Participants gave preference to the treatment perceived as having stronger evidence. Participants also reflected on positive or negative experiences with both of the interventions, counting their own experiences, as well as those of trusted sources. Lastly, participants considered their own unique circumstances and factors such as the amount of work involved, fit with personality, or fit with their "type" of insomnia., Conclusions: Knowledge of the evidence base, past experience, and personal factors shaped patient preference regardless of whether they accurately represent the evidence. Acknowledging these salient factors may help inform patient-centered decision-making and care.

Purpose: We investigated fundus autofluorescence (FAF) lifetimes in patients with retinitis pigmentosa (RP) using fluorescence lifetime imaging ophthalmoscopy (FLIO)., Methods: A total of 33 patients (mean age, 40.0 ± 17.0 years) with RP and an age-matched healthy group were included. The Heidelberg FLIO was used to detect FAF decays in short (SSC; 498-560 nm) and long (LSC; 560-720 nm) spectral channels. We investigated a 30° retinal field and calculated the amplitude-weighted mean fluorescence lifetime (τ m ). Additionally, macular pigment measurements, macular optical coherence tomography (OCT) scans, fundus photographs, visual fields, and fluorescein angiograms were recorded. Genetic studies were performed on nearly all patients., Results: In RP, FLIO shows a typical pattern of prolonged τ m in atrophic regions in the outer macula (SSC, 419 ± 195 ps; LSC, 401 ± 111 ps). Within the relatively preserved retina in the macular region, ring-shaped patterns were found, most distinctive in patients with autosomal dominant RP inheritance. Mean FAF lifetimes were shortened in rings in the LSC. Central areas remained relatively unaffected., Conclusions: FLIO uniquely presents a distinct and specific signature in eyes affected with RP. The ring patterns show variations that indicate genetically determined pathologic processes. Shortening of FAF lifetimes in the LSC may indicate disease progression, as was previously demonstrated for Stargardt disease. Therefore, FLIO might be able to indicate disease progression in RP as well., Translational Relevance: Hyperfluorescent FLIO rings with short FAF lifetimes may provide insight into the pathophysiologic disease status of RP-affected retinas potentially providing a more detailed assessment of disease progression.