Systematic review of long-term effectiveness of endoscopic gastrojejunostomy in patients presenting with gastric outlet obstruction from periampullary malignancies.

BACKGROUND: Recently, endoscopic ultrasound-guided (EUS) gastrojejunostomy (GJ) has emerged as an alternative option to surgical palliation and endoscopic duodenal stenting for malignant gastric outlet obstruction (GOO). Although early success rates are commonly reported with the technique, there is a paucity of data regarding the long-term efficacy of this approach. In this study, we investigated long-term outcomes in patients that underwent EUS-guided GJ for palliation of periampullary malignancies. METHODS: From a total of 192 studies that were reviewed, 6 studies with a follow-up time frame of a minimum of 5 months were analyzed, totaling 238 patients. Outcome variables included technical success rate, clinical success rate, adverse events, symptom recurrence, and re-intervention rates. RESULTS: The cohort of 238 patients had a technical success rate of 93.7% and a clinical success rate of 92.9%. A total of 25 patients (10.5%) experienced adverse events associated with EUS-GJ. A total of 14 patients (5.9%) experienced recurrence of GOO symptoms within 5 months. A total of 14 patients (5.9%) underwent re-intervention with the first 5 months. CONCLUSIONS: This systematic review shows that data are scarce regarding long-term effectiveness of EUS-guided GJ. Even though early success rates have been reported, further studies are needed to focus on long-term efficacy of this approach. Until such studies become available, surgical palliation should continue to be the treatment of choice for patients with malignant GOO with a prolonged life expectancy.

Differences in evaluation and management coding of outpatient clinic visits for patients undergoing elective spine surgery with use of a standardized template.

Background: In a large teaching institution with providers of various levels of training and backgrounds, and a coding department responsible for all evaluation and management (E&M) billing, variations in documentation can hinder accurate medical management and compensation. The purpose of this study is to assess differences in re-imbursement between templated and non-templated outpatient documentation for patients who eventually underwent single level lumbar microdiscectomy and anterior cervical discectomy and fusion (ACDF) both before and after the E&M billing changes were implemented in 2021. Methods: Data was collected from three spine surgeons on 41 patients who underwent a single level lumbar microdiscectomy at a tertiary care center from July 2018 to June 2019 and 35 patients seen by four spine surgeons from January through December of 2021 given the new E&M billing changes. ACDF data was collected for 52 patients between 2018 and 2019 for three spine surgeons and 30 patients from January through December of 2021 from four spine surgeons. Billing level was decided by independent coders for preoperative visits. Results: During the study period from 2018-2019 for lumbar microdiscectomy, each surgeon averaged about 14 patients. Results showed variability of billing level between the three spine surgeons (surgeon 1, 3.2±0.4; surgeon 2, 3.5±0.6; and surgeon 3, 2.9±0.8). Interestingly, even after the implementation of the 2021 E&M billing changes, there was a statistically significant increased level of billing for templated notes for lumbar microdiscectomy (P=0.013). However, this did not translate to the clinic visits for patients who underwent ACDF in 2021. When data was aggregated for all the patients from 2021 who either underwent lumbar microdiscectomy or ACDF, using a template still resulted in a statistically significant higher level of billing (P<0.05). Conclusions: Utilization of templates for clinical documentation reduces variability in billing codes. This impacts subsequent reimbursements and potentially prevents significant financial losses at large tertiary care facilities.

Current and potential roles of immuno-PET/-SPECT in CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapies have evolved as breakthrough treatment options for the management of hematological malignancies and are also being developed as therapeutics for solid tumors. However, despite the impressive patient responses from CD19-directed CAR T-cell therapies, ~ 40%-60% of these patients' cancers eventually relapse, with variable prognosis. Such relapses may occur due to a combination of molecular resistance mechanisms, including antigen loss or mutations, T-cell exhaustion, and progression of the immunosuppressive tumor microenvironment. This class of therapeutics is also associated with certain unique toxicities, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and other "on-target, off-tumor" toxicities, as well as anaphylactic effects. Furthermore, manufacturing limitations and challenges associated with solid tumor infiltration have delayed extensive applications. The molecular imaging modalities of immunological positron emission tomography and single-photon emission computed tomography (immuno-PET/-SPECT) offer a target-specific and highly sensitive, quantitative, non-invasive platform for longitudinal detection of dynamic variations in target antigen expression in the body. Leveraging these imaging strategies as guidance tools for use with CAR T-cell therapies may enable the timely identification of resistance mechanisms and/or toxic events when they occur, permitting effective therapeutic interventions. In addition, the utilization of these approaches in tracking the CAR T-cell pharmacokinetics during product development and optimization may help to assess their efficacy and accordingly to predict treatment outcomes. In this review, we focus on current challenges and potential opportunities in the application of immuno-PET/-SPECT imaging strategies to address the challenges encountered with CAR T-cell therapies.

PET Imaging of Active Invasive Fungal Infections with d-[5-11C]-Glutamine.

The increasing prevalence and severity of invasive fungal infections (IFIs), especially in immunocompromised populations, has amplified the need for rapid diagnosis of fungal pathogens. Radiotracers derived from d-amino acids (DAAs) show promise as bacterial-specific positron emission tomography (PET) imaging agents due to their preferential consumption by bacteria and largely nonutilization by hosts. Unlike mammals, fungi can utilize external DAAs including d-glutamine for their growth by rapidly upregulating DAA oxidases. Additionally, glutamine is essential for fungal nitrogen assimilation, survival, and virulence. We previously validated d-[5-11C]-glutamine (d-[5-11C]-Gln) as an efficient radiotracer targeting live bacterial soft-tissue infections. Here, we further expanded this investigation to evaluate its translational potential for PET imaging of IFIs in immunocompetent mouse models subcutaneously (SubQ) and intramuscularly (IM) infected with Candida albicans (C. albicans), using its l-isomer counterpart (l-[5-11C]-Gln) as a control. Comparative studies between pathogens showed significantly (p < 0.05) higher uptake in fungi (C. albicans and C. tropicalis) versus tested bacterial species for d-[5-11C]-Gln, suggesting that it could potentially serve as a more sensitive radiotracer for detection of fungal infections. Additionally, comparative PET imaging studies in immunocompetent infected mice demonstrated significantly higher infection-to-background ratios for d- versus l-[5-11C]-Gln in both SubQ (ratio = 1.97, p = 0.043) and IM (ratio = 1.97, p = 0.028) infections. Fungal infection imaging specificity was confirmed with no significant difference observed between localized inflammation sites versus untreated muscle background (heat-killed injection site/untreated muscle: ∼1.1). Taken together, this work demonstrates the translational potential of d-[5-11C]-Gln for noninvasive PET imaging of IFIs.

Can the LACE index help identify uninsured patients at risk of loss to follow-up during a pharmacist-led transitions of care program?

BACKGROUND: Uninsured patients are susceptible to being lost to follow-up (LTFU). In addition to being uninsured, follow-up is especially critical among this population during transitions of care when patients are discharged from the hospital setting back to home because follow-up care after discharge has been proven to prevent readmissions. The LACE tool has historically been used to predict readmissions, but the LACE tool has not been used to evaluate patients' risk of LTFU. OBJECTIVE: To understand the potential translation of the LACE tool for use in uninsured patients' follow-up care, we assessed the association between LACE index scores and patients' risk of LTFU during a pharmacist-led transitions of care program for uninsured patients. METHODS: Data were extracted from a randomized controlled trial implementing a pharmacist-led transitions of care program at an indigent care clinic. The study population included uninsured adult patients (>18 years old) who spoke English and attended a clinical visit with a pharmacist within 16 days after discharge from a community hospital. Analyses sought to determine factors associated with the patients' LTFU status. RESULTS: Among 88 enrolled participants, 29 participants (32.95%) were LTFU. Thirty-two patients (36.4%) had a high LACE index score at baseline, indicating an increased risk of 30-day readmission. Of the remaining 56 patients (63.6%) with low-to-moderate LACE index scores, 54 (61.4%) had a moderate LACE index score, and only 2 (2.3%) had a low LACE index score. Uninsured patients with high LACE index scores had 70% lower odds of being LTFU than uninsured patients with low-to-moderate LACE index scores (exact odds ratio 0.297 [95% CI 0.081-0.947]). CONCLUSION: The LACE index score was inversely related to the risk of LTFU during a pharmacist-led transitions of care program. Pharmacists may use the LACE tool to identify patients at high risk of LTFU.

What Are the Risk Factors for an Upper Extremity Deep Venous Thrombosis After Orthopaedic Irrigation and Debridement and Peripherally Inserted Central Catheter Placement?

BACKGROUND: Peripherally inserted central catheter (PICC) placement is necessary for delivery of intravenous (IV) antibiotics to treat bone and soft tissue infections. Upper extremity deep venous thrombosis (DVT) after PICC placement is a complication with unknown incidence in the orthopaedic literature. The major objectives of this study are Identifying the rate of upper extremity PICC-associated DVTs after orthopaedic procedures;Which orthopaedic subspecialties are most likely to encounter an upper extremity PICC-associated DVT?What surgeries or medical comorbidities are risk factors for upper extremity PICC-associated DVTs?Does type of DVT chemoprophylaxis decrease the risk of an upper extremity PICC-associated DVT? METHODS: A retrospective review of electronic medical records (EMR) was performed to include all patients undergoing irrigation and debridement (I&D) for treatment of orthopaedic surgery-related infections over a 10-year period. All patients with PICC placement were included for analyses. Age, sex, and medical comorbidities were extracted from the EMR. Mann-Whitney non-parametric tests, Fisher's exact tests, Chi-square tests, and Cochran-Mantel-Haenszel (CMH) tests were used to determine associations with DVT events for those with PICCs based on medical comorbidities, PICC lumen size, team placing the PICC, impact of implant removal, and protective effect of DVT chemoprophylaxis. Significance was set at p<0.05. RESULTS: Twenty-one of 660 patients (3.18% rate) were found to have an upper extremity PICC-associated DVT. A history of DVT (OR=8.99 [95% CI: 3.39, 49.42]) was significantly associated with an upper extremity PICC-associated DVT. The greatest risk for an upper extremity PICC-associated DVT was intramedullary implant removal (OR=12.43 [95% CI: 3.13, 49.52]). The type of DVT chemoprophylaxis did not significantly affect the likelihood of an upper extremity PICC-associated DVT. CONCLUSION: Intramedullary implant removal and a history of DVT are risk factors for an upper extremity PICC-associated DVT. The results of this study should be of particular interest to surgeons who do not typically give DVT prophylaxis and plan to perform surgery on patients with CHF, a history of a DVT, or plan to manipulate the intramedullary canal.

Responsiveness of routine diagnostic tests for vertebral osteomyelitis may be influenced by the infecting organism.

BACKGROUND CONTEXT: Vertebral osteomyelitis (VO) becomes increasingly more prevalent as people age, and it is a condition seen frequently by referral center spine surgeons. It can take as long as 6 months for a proper diagnosis to be made. Staphylococcus aureus (S. aureus) is the most common isolated organism in up to 80% of the affected population. The clinical presentation of vertebral osteomyelitis is typically non specific (back pain), which can make timely diagnosis challenging. Fever is often absent. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC) and serum polymorphonuclear leukocyte percentage (PMN%) are traditionally used as first-line tests because of their perceived sensitivity to help diagnose vertebral osteomyelitis. It is not known whether these test values are affected by the infecting organism. PURPOSE: To determine whether individual first-line diagnostics differed based on infecting organism and whether certain organisms are associated with lower lab values. Additionally, this study sought to determine if VO caused by lower virulent (eg, culture-negative and nonpyogenic organisms) could contribute to delays in treatment due to lack of elevated biomarkers. STUDY DESIGN/SETTING: Single-center retrospective cohort study. PATIENT SAMPLE: We reviewed clinical data of 133 patients (60% male) diagnosed with VO from 2015-2019 in a US Midwest academic hospital. OUTCOMES MEASURES: Primary outcome measures included the maximum temperature upon presentation, serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and percentage neutrophils during the hospital admission. METHODS: Inclusion criteria were adult patients diagnosed with vertebral osteomyelitis who underwent blood culture and/or biopsy prior to treatment. All patients enrolled in the study were diagnosed with VO and confirmed via magnetic resonance imaging (MRI). MRI findings associated with VO included destruction of endplates, increased signal in vertebral bodies, and the surrounding disc on T2-weighted imaging were confirmed. The patients had laboratory work up and clinical follow up regardless of positive culture or negative culture. The mean peak inflammatory marker levels were compared among organisms with student's t test. Demographics, comorbidities, and CCI were collected and multivariable logistic regression models were used. Receiver operating characteristic curve analysis was performed to delineate separate, optimal cut offs for CRP, ESR, WBC, and PMN% for patients with culture positive osteomyelitis RESULTS: Patients' average age was 57.0±13.7 years with a mean BMI of 30.5±9.70 kg/m2, and a mean Charleston Comorbidity Index (CCI) of 3.17±2.35. Staphylococcus aureus and antibiotic resistant organisms (MRSA and VRE) demonstrated a higher mean CRP and ESR than culture negative, fungal and TB cases. Staphylococcus aureus, antibiotic resistant organisms, and coagulase negative Staphylococcus demonstrated a higher mean WBC than culture negative as well as fungal and TB cases. Staphylococcus aureus, antibiotic resistant organisms, coagulase negative Staphylococcus, and Streptococcus species had a higher mean peak PMN%, than culture negative as well as fungal and TB case. Temperature did not correlate with a diagnosis of osteomyelitis. CONCLUSIONS: Serum laboratory markers in the diagnosis of VO appear to be influenced by the infecting organism type. Laboratory values in patients diagnosed with VO with culture negative or non-pyogenic organisms are lower compared to antibiotic resistant and S. aureus organisms. Fever did not correlate with a diagnosis of VO.

Implementation of a pharmacist-led transitions of care program in an indigent care clinic: A randomized controlled trial.

OBJECTIVES: Pharmacists' involvement in the transitions of care has shown the potential to decrease readmissions and increase access to care in many populations; however, the uninsured patient populations have not been studied. The evidence for the feasibility of implementing transitions of care services in indigent care clinics with limited resources also remains limited. The objectives were to implement a pharmacist-led transitions of care program in an indigent care clinic, to demonstrate the feasibility of its implementation, and to evaluate its impact on readmissions and emergency department (ED) visit rates among an uninsured population. METHODS: The study was a single-blind, parallel, randomized controlled trial implemented in an indigent care clinic in the Southeast region of the United States from October 2018 to July 2019. Eligible patients were those older than 18 years, uninsured, English-speaking, diagnosed with any condition, and recently discharged from a local community hospital within the past 16 days. The primary outcome was the hospital readmission rate at 30 days after discharge. The secondary outcomes included 60- and 90-day readmission rates in addition to 30-, 60-, and 90-day ED visit rates. RESULTS: A total of 88 participants were recruited. The intervention was successfully implemented in the clinic, but patient-level barriers to follow-ups included transportation, accessibility, financial burdens, inconsistent telephone communication, and a lack of knowledge about the importance of follow-ups. At 30 days postdischarge, 13.64% of the patients in the usual care group experienced readmissions compared with 9.30% of the patients in the intervention group. The relative change in the 30-day readmission rates between the usual care and the intervention groups was 1.7 (rate ratio [RR] 1.69 [95% CI 0.47-6.08]). The RRs were insignificant for the 30-, 60-, and 90-day readmission and ED visit rates. CONCLUSION: This study demonstrated the feasibility of implementing transitions of care services in a clinic with limited resources by pharmacists. The intervention showed promising results by reducing readmission rates.

Hypoxia-inducible factor prolyl hydroxylase inhibitors: a paradigm shift for treatment of anemia in chronic kidney disease?

INTRODUCTION: The hypoxia-inducible factor prolyl hydroxylase (HIF-PH) pathway is responsible for regulating the biosynthesis of erythropoietin (EPO) and maintaining iron homeostasis. Investigational drugs that target the HIF-PH pathway are promising alternatives for treating anemia in Chronic Kidney Disease (CKD). AREAS COVERED: This review summarizes recent advances focused on the clinical development of HIF-PH inhibitors (HIF-PHIs) as potentially novel therapies in the treatment of anemia in CKD based on publications available on PubMed and restricted Google searches. We provide a comparison between HIF-PHIs regarding their pharmacokinetics, dosing regimens and safety concerns, structure-activity relationships, and alterations in key laboratory parameters observed in animal models and clinical trials. EXPERT OPINION: HIF-PHIs may be advantageous in some aspects compared to the conventional erythropoiesis-stimulating agents (ESAs). While ESAs could increase the risk of cardiovascular events due to rapid rises in ESA blood levels, HIF-PHIs have been reported to maintain EPO concentrations at levels that are closer to the normal physiological ranges. Although HIF-PHIs have been demonstrated to be relatively safe and effective in clinical trials, long-term safety data are needed in order to establish whether these therapeutic agents will lead to a major paradigm change in the treatment of anemia of CKD.

Hypersomnias of central origin.

This article presents a succinct understanding of how to diagnose and manage hypersomnias of central origin, including narcolepsy, idiopathic hypersomnia, and recurrent hypersomnias.

The relation between cognitive functioning and self-reported sleep complaints in nondemented older adults: results from the Bronx aging study.

Self-reported sleep complaints and current cognitive functioning were assessed in 375 nondemented participants ages 75 to 85 years (134 men and 241 women) as part of enrollment in the Bronx aging study, an ongoing longitudinal community-based study of cognitive aging. This study only reports on the baseline data collected from 1980 to 1983. Sleep complaints were common, occurring in about 25% of the sample. Furthermore, after controlling for depression, use of hypnotic medication, physical morbidity, age, and education, participants who reported longer sleep onset latencies performed significantly worse on measures of verbal knowledge, long-term memory and fund of information, and visuospatial reasoning. Participants who reported longer sleep durations did significantly worse on a measure of verbal short-term memory. These results suggest that perceived sleep is related to select objective cognitive abilities even when accounting for commonly recognized mediating variables, such as depression, medical comorbidity, age, or use of hypnotic medication. Given the restricted range of this nondemented sample, these results may underestimate the relation between cognitive abilities and sleep.