Inferior Outcomes for Patients Transferred Between Surgical Stages for Knee Periprosthetic Joint Infection.

BACKGROUND: Periprosthetic joint infection (PJI) in total knee arthroplasty may result in 2-stage revision surgery. There are limited data describing outcomes when the first stage is completed at an outside hospital and the patient is referred to a tertiary center. We hypothesized that patients have greater success when both surgeries occur at a single center. METHODS: There were 25 knee PJI patients who presented with an antibiotic spacer and had a minimum 2-year follow-up who were retrospectively identified at a single tertiary referral center from 2014 to 2021. A cohort matched for age, sex, body mass index, Elixhauser comorbidity measure, spacer type, infectious organism, and year of surgery was established with patients who had both stages completed at the investigating institution. Modified Delphi success criteria of no subsequent surgery or reinfection with any species were compared. RESULTS: The transferred group demonstrated a treatment success of 40% compared to 84% in the continuous group (P < .01). The transferred group was more likely to have an additional procedure between stages (44 versus 8%, P < .01), with a higher number of surgeries after primary total knee arthroplasty (4.8 versus 3.0, P < .01), between stages (1.4 versus 0.2, P < .01), and after second stage (0.8 versus 0.2, P = .03). The transferred group had longer durations between stages (20.1 versus 7.0 weeks, P < .01). CONCLUSION: Patients who have PJIs transferred between stages demonstrated higher treatment failure. Surgeons should consider transfer early with a goal of continuous management by a single institution.

Primary Aortoenteric Fistula in a Patient With Prior Abdominopelvic Surgery and Opioid-Induced Constipation.

Aortoenteric fistulas (AEF) represent a rare, life-threatening cause of gastrointestinal bleeding with an incidence of 0.007 per million. Iliac artery-enteric fistulas represent an even more uncommon variant of AEFs. Prompt diagnosis and intervention are required to prevent associated morbidity and mortality. Herein, we report a rare case of iliac-enteric fistula in a patient with hematochezia.

Pyrocarbon hemiarthroplasty of the shoulder: a systematic review and meta-analysis of clinical results.

BACKGROUND: Hemiarthroplasty is often considered in the setting of preserved glenoid cartilage given the high risk of revision associated with total shoulder arthroplasty. Pyrocarbon (PyC) has been used as an implant material that theoretically allows for formation of a neo-membrane that would act like cartilage to reduce glenoid wear. The purpose of this study was to evaluate the clinical outcomes, radiographic outcomes, revision rates, and complication rates in the existing literature on shoulder hemiarthroplasty using PyC. METHODS: The MEDLINE, Embase, and Scopus databases were searched for articles relating to shoulder hemiarthroplasty using the terms "pyrocarbon" or "pyrolytic carbon." Abstracts and articles were screened against predefined inclusion and exclusion criteria, with a minimum of 24 months' follow-up required. Data on patient demographic characteristics, clinical outcome scores, complications, revision rates, and radiographic findings were recorded. Where appropriate, meta-analysis was performed. RESULTS: Twelve studies were selected for final inclusion, with a total of 536 patients. Among the studies reporting preoperative and postoperative range of motion (ROM), an overall improvement in ROM was observed. The mean Constant score was 70.9 points postoperatively, with a mean improvement of 36.2 points (n = 359, 9 studies). Radiographically, 22.8% of patients (n = 536, 8 studies) had evidence of glenoid erosion, 10.4% had changes in implant positioning, and 9.9% had tuberosity thinning. In addition, 1.5% of patients had radiographic subacromial space reduction, whereas 0.7% had an increase in tuberosity thickness. Across all studies, there was an 8.6% complication rate, with the most common cause being glenoid erosion (2.6%, n = 14). There was an overall 7.7% revision rate (n = 41), with 63% of revisions (n = 26) undergoing conversion to reverse or total shoulder arthroplasty. CONCLUSION: PyC hemiarthroplasty shows overall improvements in ROM and patient-reported outcomes for patients. However, there remains concern for glenoid erosion on radiographic evaluation at minimum 2-year follow-up. Although preliminary studies have shown encouraging results, this systematic review emphasizes the need for longer-term follow-up studies with further radiographic evaluation of the severity of glenoid erosion and the association with functional outcomes and failure risk.

Effectiveness of convolutional neural networks in the interpretation of pulmonary cytologic images in endobronchial ultrasound procedures.

BACKGROUND: Rapid on-site cytologic evaluation (ROSE) helps to improve the diagnostic accuracy in endobronchial ultrasound (EBUS) procedures. However, cytologists are seldom available to perform ROSE in many institutions. Recent studies have investigated the application of deep learning in cytologic image analysis. As such, the present study analyzed lung cytologic images obtained by EBUS procedures, and employed deep-learning methods to distinguish between benign and malignant cells and to semantically segment malignant cells. METHODS: Ninety-seven patients who underwent 104 EBUS procedures were enrolled. Four hundred and ninety-nine lung cytologic images obtained via ROSE, including 425 malignant and 74 benign, and most malignant were lung adenocarcinoma (64.3%). All the images were used to train a residual network model with 101 layers (ResNet101), with suitable hyperparameters selected to classify benign and malignant lung cytologic images. An HRNet model was also employed to mark the area of malignant cells. Automatic patch-cropping was adopted to facilitate dataset preparation. RESULTS: Malignant cells were successfully classified by ResNet101 with 98.8% classification accuracy, 98.8% sensitivity, and 98.8% specificity in patch-based classification; 95.5% classification accuracy in image-based classification; and 92.9% classification accuracy in patient-based classification. Malignant cell area was successfully marked by HRNet with a mean intersection over union of 89.2%. The automatic cropping method enabled the system to complete diagnosis within 1 s. CONCLUSIONS: This is the first study to combine lung cytologic image deep-learning classification with semantic segmentation. The model was optimized for high accuracy and the automatic cropping facilitates the clinical application of our model. The success in both lung cytologic images classification and semantic segmentation on our dataset shows a promising result for clinical application in the future.

Epidemiology of chronic kidney disease of undetermined aetiology in Taiwanese farmers: a cross-sectional study from Changhua Community-based Integrated Screening programme.

OBJECTIVES: Chronic kidney disease of undetermined or non-traditional aetiology (CKDu or CKDnT) has been reported in Mesoamerica among farmers under heat stress. Epidemiological evidence was lacking in Asian countries with similar climatic conditions. The objective of this study was to investigate the prevalence of CKDu and possible risk factors. METHODS: We used the data from the Changhua Community-based Integrated Screening programme from 2005 to 2014, which is the annual screening for chronic diseases in Taiwan's largest rice-farming county since 2005. Our study population included farmers and non-farmers aged 15-60 years. CKDu was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 at age under 60 years without hypertension, diabetes, proteinuria, haematuria or using Chinese herbal medicine. We estimated the adjusted prevalence OR (POR) of CKDu by farmers, age, sex, education, urbanisation, smoking, body mass index, hyperuricaemia, hyperlipidaemia, heart disease and chronic liver disease. RESULTS: 5555 farmers and 35 761 non-farmers were included in this study. CKDu accounted for 48.9% of all CKD cases. The prevalence of CKDu was 2.3% in the farmers and 0.9% in the non-farmers. The crude POR of CKDu in farmers compared with non-farmers was 2.73 (2.13-3.50), and the adjusted POR was 1.45 (1.10-1.90). Dehydration (blood urea nitrogen-to-creatinine ratio >20) was found in 22% of the farmers and 14% of the non-farmers. CONCLUSIONS: Farmers in subtropical Asian countries are at increased risk of CKDu. Governments should take the CKDu epidemics seriously and provide farmers with occupational health education programmes on thermal hazards.

Patient-reported Quality of Life Following Stereotactic Body Radiotherapy and Conventionally Fractionated External Beam Radiotherapy Compared with Active Surveillance Among Men with Localized Prostate Cancer.

BACKGROUND: Evidence supporting the efficacy of stereotactic body radiotherapy (SBRT) for localized prostate cancer is accumulating, but comparative studies of patient-reported quality of life (QOL) following SBRT versus conventionally fractionated external beam radiotherapy (EBRT) or active surveillance (AS) are limited. OBJECTIVE: To compare QOL of patients pursuing SBRT and EBRT versus AS. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort of 680 men with newly diagnosed localized prostate cancer was prospectively enrolled from 2011 to 2013. INTERVENTION: SBRT, EBRT without androgen deprivation therapy, or AS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: QOL was prospectively assessed before treatment (baseline), and at 3, 12, and 24mo after treatment using the validated Prostate Cancer Symptom Indices, which contain four domains: sexual dysfunction, urinary obstruction/irritation, urinary incontinence, and bowel problems. Propensity weighting via logistic regression models was used to balance baseline characteristics, and the mean QOL scores of EBRT and SBRT patients were compared against AS patients as the control group. RESULTS AND LIMITATIONS: Compared with AS patients, EBRT patients had worse urinary obstructive/irritative symptoms and sexual dysfunction at 3mo, and worse bowel symptoms at 3 and 24mo. SBRT patients had similar scores as AS patients in all domains and across all time points; however, due to small sample size, worse sexual function and urinary incontinence in SBRT patients cannot be ruled out. Further research is needed to assess long-term outcomes. CONCLUSIONS: In a nonrandomized cohort of men with localized prostate cancer, SBRT appeared to result in favorable QOL results through 2yr of follow-up, but worse sexual function and urinary incontinence compared with AS cannot be ruled out completely. Larger studies with longer follow-up are needed to confirm these findings. PATIENT SUMMARY: Stereotactic body radiotherapy (SBRT) and active surveillance appear to have similar quality of life outcomes through 2yr, although worse sexual function and urinary incontinence from SBRT cannot be ruled out completely.

Specialty Drug Price Trends in the Federal 340B Drug Discount Program.

BACKGROUND: The federal 340B Drug Discount Program provides access to significant drug price discounts for health care organizations in the United States that serve a disproportional share of disadvantaged patients. OBJECTIVE: To analyze trends over a 10-year period (2006~2016) in the price of specialty drugs, contrasting the market price with the price paid under the 340B program. METHODS: Pharmacy purchase records, including the 340B drug price and the wholesale acquisition cost (WAC), were collected from a 340B-contract pharmacy group in Southern California between 2006 and 2016. Records were used to calculate price changes in the annual average price paid. The average price was calculated as the weighted price, using purchasing volume for each year as weights. Separate time series of year-to-year price changes were created by therapeutic class using the American Hospital Formulary Service Therapeutic Classification system. RESULTS: The 340B price growth rate patterns were similar to the profile of the WAC prices over time across all drug classes. The overall drug price growth rate per year over 10 years for WAC prices was 15% and 10% for 340B prices. For specialty drug classes, the average growth rates per year were 14% for the WAC price and 6% for the 340B price. For certain specialty drug classes, such as antineoplastic and antiretroviral drugs, the 340B price inflation rates were significantly lower than the WAC price inflation rates after 2013. CONCLUSIONS: The price inflation of specialty drugs exceeds the rate of inflation in the Consumer Price Index for prescription drugs. The 340B price shows a similar inflation pattern as the WAC price over time in the specialty drug categories. DISCLOSURES: This study is 1 of 3 research projects that comprise Lee's dissertation. Funding to support Lee's dissertation research was provided as an unrestricted fellowship from PharMedQuest Pharmacy Services. Chang is employed by PharMedQuest Pharmacy Services, which provided the dataset for analysis. Lee reports grants from PharMedQuest Pharmacy Services, unrelated to this study. McCombs has nothing to report.

Photobiomodulation therapy in the management of chronic oral graft-versus-host disease.

AIM: Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) may experience oral complications associated with chronic graft-versus-host disease (cGVHD). These complications may significantly affect quality of life, even many years post-HSCT. Current treatment options for oral cGVHD are limited and often include steroid or other immunomodulatory medications, which may not adequately control the oral condition. A non-immunosuppressive intervention for symptomatic relief in oral cGVHD would thus be a welcome addition to the treatment paradigm. MATERIALS AND METHODS: We report seven cases of oral cGVHD that were treated with photobiomodulation therapy (PBM), previously known as low-level laser therapy (LLLT). Patients underwent at least two PBM treatments per week in addition to local treatment with steroids, and if on systemic therapies, these were either unchanged or dosage was reduced during the period of PBM therapy. Follow-up data is presented for 4 weeks of treatment. RESULTS: Oral pain, sensitivity, and dry mouth improved in most patients. These findings suggest PBM therapy may represent an additional approach for management of oral cGVHD, and suggest that controlled studies should be conducted to confirm the efficacy and safety of PBM therapy in oral cGVHD and to determine optimal PBM therapy protocols.

Assessment of Multipotent Mesenchymal Stromal Cells in Bone Marrow Aspirate From Human Calcaneus.

Bone marrow aspirates (BMAs), owing to their innate osteogenic potential, are well-documented supplements to osteoconductive and/or osteoinductive materials. The calcaneal body provides foot and ankle surgeons a convenient harvest site with low morbidity and minimal cost. In the present study, we sought to identify and characterize multipotent mesenchymal stromal cells (MSCs) in BMAs harvested from the human calcaneal body. Ten healthy patients aged 18 to 65 years were enrolled in the present study. BMAs were harvested from the patients without any reported postoperative complications related to the harvest. Cells isolated from all the aspirates were adherent to culture plates and expressed positive MSC surface markers (CD105, CD90, and CD73) and a low level of negative MSC markers (CD34 and CD45). The cells maintained the ability to proliferate and differentiate into cells of mesenchymal lineages. The BMAs from the human calcaneal body offer a healthy source of multipotent MSCs.

Adaptor complex AP2/PICALM, through interaction with LC3, targets Alzheimer's APP-CTF for terminal degradation via autophagy.

The hallmarks of Alzheimer's disease (AD) are the aggregates of amyloid-ß (Aß) peptides and tau protein. Autophagy is a major cellular pathway leading to the removal of aggregated proteins. We have reported recently that autophagy was responsible for amyloid precursor protein cleaved C-terminal fragment (APP-CTF) degradation and amyloid ß clearance in an Atg5-dependent manner. Here we aimed to elucidate the molecular mechanism by which autophagy mediates the degradation of APP-CTF and the clearance of amyloid ß. Through affinity purification followed by mass spectrum analysis, we identified adaptor protein (AP) 2 together with phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM) as binding proteins of microtubule-associated protein 1 light chain 3 (LC3). Further analysis showed that AP2 regulated the cellular levels of APP-CTF. Knockdown of AP2 reduced autophagy-mediated APP-CTF degradation. Immunoprecipitation and live imaging analysis demonstrated that AP2 and PICALM cross-link LC3 with APP-CTF. These data suggest that the AP-2/PICALM complex functions as an autophagic cargo receptor for the recognition and shipment of APP-CTF from the endocytic pathway to the LC3-marked autophagic degradation pathway. This molecular mechanism linking AP2/PICALM and AD is consistent with genetic evidence indicating a role for PICALM as a risk factor for AD.

Calcium phosphate combination biomaterials as human mesenchymal stem cell delivery vehicles for bone repair.

A new class of biomimetic, bioresorbable apatitic calcium phosphate cement (CPC) was recently developed. The handling characteristics, and the ability to harden at body temperature in the presence of physiological saline, make this material an attractive clinical bone substitute and delivery vehicle for therapeutic agents in orthopedic applications. The major challenge with the material is formulating an injectable paste with options for cell delivery, in order to regenerate new bone faster and with high quality. In this study, three different additives and/or viscosity modifiers (carboxymethylcellulose, silk, and alginate) were incorporated into a CPC matrix. Injectability, cell viability, cell proliferation, surface morphology, and gene expression for osteogenesis of hMSCs were all evaluated. Injectable CPC-gel composites with cell protection were achieved. The CPC modified with alginate provided the best results based on cell proliferation, ALP and collagen production, and osteogenic transcript increases (for ALP, type I collagen, BSP, and OP). Furthermore, osteogenic analysis indicated lineage-specific differentiation of hMSCs into osteogenic outcomes. The results suggest that CPC mixed with alginate can be used as a cell delivery vehicle for bone regeneration.

The use of human acellular dermal matrix for the correction of secondary deformities after breast augmentation: results and costs.

BACKGROUND: Secondary breast deformities following breast augmentation constitute some of the most challenging and difficult problems to correct. Although the application and efficacy of human acellular dermal matrix in breast reconstruction has been previously reported, there is little information in the literature relating to its indications, results, or cost in aesthetic breast surgery. METHODS: This study retrospectively reviewed a single surgeon's experience in correcting secondary deformities with human acellular dermal matrix after breast augmentation from 2005 to 2009. A total of 23 patients (38 breasts) were included in the study. RESULTS: There were 28 breasts with surface irregularities and 22 breasts with implant malposition (12 had both). On average, 1.13 sheets of human acellular dermal matrix were used per breast per operation. At the authors' institution, this material equates to a cost to the patient of $3536 to $4856 per breast (depending on sheet size and thickness). Twenty of 23 patients (87 percent) [32 of 38 breasts (84 percent)] had improvement in their breast deformity after breast revision surgery. Three patients (six breasts) needed another cosmetic breast operation before the end of the follow-up period: two because of persistent surface irregularities and one with a request for larger implants. One patient (3 percent) had an infection in one breast, requiring removal of the human acellular dermal matrix. CONCLUSIONS: Human acellular dermal matrix is a useful and safe adjunct for correction of contour deformities after breast augmentation. Its high cost, however, may be a deterrent to widespread use in self-pay patients.

The CLN3 gene is a novel molecular target for cancer drug discovery.

Juvenile Batten disease is a neurodegenerative disease caused by accelerated apoptotic death of photoreceptors and neurons attributable to defects in the CLN3 gene. CLN3 is antiapoptotic when overexpressed in NT2 neuronal precursor cells. CLN3 negatively modulates endogenous ceramide levels in NT2 cells and acts upstream of ceramide generation. Because defects in regulation of apoptosis are involved in the development of cancer, we evaluated the expression of CLN3 on both mRNA and protein levels in a variety of cancer cell lines and solid colon cancer tissue. We also observed the effect of the blocking of CLN3 protein expression on cancer cell growth, survival, ceramide production, and apoptosis by using an adenovirus-bearing antisense CLN3 construct. We show that CLN3 mRNA and protein are overexpressed in glioblastoma (U-373G and T98g), neuroblastoma (IMR-32 and SK-N-MC), prostate (Du145, PC-3, and LNCaP), ovarian (SK-OV-3, SW626, and PA-1), breast (BT-20, BT-549, and BT-474), and colon (SW1116, SW480, and HCT 116) cancer cell lines but not in pancreatic (CAPAN and As-PC-1) or lung (A-549 and NCI-H520) cancer cell lines. CLN3 is also up-regulated in mouse melanoma and breast carcinoma cancer cell lines. We found CLN3 expression is 22-330% higher than in corresponding normal colon control tissue in 8 of 10 solid colon tumors. An adenovirus-expressing antisense CLN3 (Ad-AS-CLN3) blocks CLN3 protein expression in DU-145, BT-20, SW1116, and T98g cancer cell lines as seen by Western blot. Blocking of CLN3 expression using Ad-AS-CLN3 inhibits growth and viability of cancer cells. It also causes elevation in endogenous ceramide production through de novo ceramide synthesis and results in increased apoptosis as shown by propidium iodide and JC-1 staining. This suggests that Ad-AS-CLN3 may be an option for therapy in some cancers. More importantly these results suggest that CLN3 is a novel molecular target for cancer drug discovery.