Underrecognition and Suboptimal Quality of Care for Nonalcoholic Fatty Liver Disease Cirrhosis in Primary Care Patients with Diabetes Mellitus.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of cirrhosis but is underrecognized in primary care. Cirrhosis management requires complex monitoring, and the quality of care (QoC) for NAFLD cirrhosis patients in primary care may be inadequate. METHODS: In this retrospective-prospective cohort study of primary care patients with diabetes mellitus, we identified patients with NAFLD cirrhosis by 1) evidence of cirrhosis from abdominal imaging identified by natural language processing, or 2) existence of International Classification of Diseases code for cirrhosis. A finding of either was followed by manual chart review for confirmation of both cirrhosis and NAFLD. We then determined if cirrhosis care measures were up-to-date, including hepatitis A and B vaccination, Model for End-Stage Liver Disease score components, esophagogastroduodenoscopy, and hepatocellular carcinoma screening. We created a composite score quantifying overall QoC (scale 0-8), with high QoC defined as ≥6 points. RESULTS: Among 3,028 primary care patients with diabetes mellitus, we identified 51 (1.7%) with NAFLD cirrhosis. Although 78% had ≥3 average primary care visits/year, only 24% completed hepatocellular carcinoma screening at least annually in at least 75% of years since diagnosis. The average QoC composite score was 4.9 (SD 2.4), and less than one-third had high QoC. CONCLUSIONS: NAFLD cirrhosis is prevalent but underdiagnosed in primary care, and receipt of comprehensive QoC was suboptimal. Given the rising incidence of NAFLD cirrhosis, primary care providers need improved awareness and mechanisms to ensure high QoC for this population.

Reliability of current classification systems for periprosthetic distal femur fractures.

INTRODUCTION: This study aims to determine which Periprosthetic Distal Femur Fracture (PDFF) classification system is the most reliable. The secondary aim was to determine which classification system correlated most accurately with the surgical management recommended and delivered. METHODS: Between 2011 and 2019, 83 patients with 83 PDFFs that extended to the femoral component of a total knee arthroplasty (TKA) were retrospectively identified from a trauma database. Minimum follow-up was 1 year. Age, BMI, time from TKA, operative management, and Nottingham Hip Fracture Scores were collected, and AP and lateral radiographs used to classify all fractures using seven established classification systems by two observers blinded to management. In patients treated operatively (n = 69), preoperative radiographs were reviewed by two surgeons with expertise in trauma and knee revision who recommended fixation or distal femoral replacement (DFR) requirement. RESULTS: Mean age was 80.7 years (SD9.4) and 50 (84.7%) were female. PDFFs occurred at a mean 9.5 years (SD5.2) after primary TKA. Mean follow-up was 3.8 years (SD2.9). Management was fixation in 47, DFR in 22 and non-operative for 14. The Fakler classification demonstrated highest interobserver reliability (ICC=0.948), followed by the Rorabeck (ICC=0.903), UCS (ICC=0.850) and Chen (ICC=0.906). The Neer classification demonstrated weakest agreement (ICC=0.633). Overall accuracy of predicting DFR requirement (as determined by two experts) was highest for the Fakler system (83.9%). Compared with actual management delivered the Rorabeck system was most accurate (94.1%). Multivariate regression demonstrated that the ultimate need for DFR (n = 22) was independently associated with medial comminution (HR 2.66 (1.12-6.35 95%CI), p = 0.027) and fractures distal to the anterior flange and posterior condyle of the femoral component (HR 2.45 (1.13-5.31), p = 0.024). CONCLUSION: The Fakler classification showed highest interobserver agreement and was most accurately predictive of the management recommended by two experts. No classification system accurately predicted the fractures that required DFR, and none included medial comminution which was independently associated with DFR requirement. There remains a need for a PDFF classification system that reliably guides operative management of PDFFs.

Loss to patient-reported outcome measure follow-up after hip arthroplasty and knee arthroplasty : patient satisfaction, associations with non-response, and maximizing returns.

AIMS: The aim of this study was to determine satisfaction rates after hip and knee arthroplasty in patients who did not respond to postoperative patient-reported outcome measures (PROMs), characteristics of non-responders, and contact preferences to maximize response rates. METHODS: A prospective cohort study of patients planned to undergo hip arthroplasty (n = 713) and knee arthroplasty (n = 737) at a UK university teaching hospital who had completed preoperative PROMs questionnaires, including the EuroQol five-dimension health-related quality of life score, and Oxford Hip Score (OHS) and Oxford Knee Score (OKS). Follow-up questionnaires were sent by post at one year, including satisfaction scoring. Attempts were made to contact patients who did not initially respond. Univariate, logistic regression, and receiver operator curve analysis was performed. RESULTS: At one year, 667 hip patients (93.5%) and 685 knee patients (92.9%) had undergone surgery and were alive. No response was received from 151/667 hip patients (22.6%), 83 (55.0%) of whom were ultimately contacted); or from 108/685 knee patients (15.8%), 91 (84.3%) of whom were ultimately contacted. There was no difference in satisfaction after arthroplasty between initial non-responders and responders for hips (74/81 satisfied vs 476/516 satisfied; p = 0.847) or knees (81/93 satisfied vs 470/561 satisfied; p = 0.480). Initial non-response and persistent non-response was associated with younger age, higher BMIs, and worse preoperative PROMs for both hip and knee patients (p < 0.050). Being in employment was associated with persistent non-response for hip patients (p = 0.047). Multivariate analysis demonstrated that younger age (p < 0.038), higher BMI (p = 0.018), and poorer preoperative OHS (p = 0.031) were independently associated with persistent non-response to hip PROMs. No independent associations were identified for knees. Using a threshold of > 66.4 years predicted a preference for contact by post (area under the curve 0.723 (95% confidence interval (CI) 0.647 to 0.799; p < 0.001, though this CI crosses the 0.7 limit considered reliable). CONCLUSION: The majority of initial non-responders were ultimately contactable with effort. Satisfaction rates were not inferior in patients who did not initially respond to PROMs. Cite this article: Bone Jt Open 2022;3(4):275-283.

Immediate weight-bearing is safe following lateral locked plate fixation of periprosthetic distal femoral fractures.

PURPOSE: This study aimed to determine whether unrestricted weight-bearing as tolerated (WBAT) following lateral locking plate (LLP) fixation of periprosthetic distal femoral fractures (PDFFs) is associated with increased failure and reoperation, compared with restricted weight-bearing (RWB). MATERIALS AND METHODS: In a retrospective cohort study of consecutive patients with unilateral PDFFs undergoing LLP fixation, patients prescribed WBAT were compared with those prescribed 6 weeks of RWB. The primary outcome measure was reoperation. Kaplan-Meier and Cox multivariable analyses were performed. RESULTS: There were 43 patients (mean age 80.9 ± 11.7 years, body mass index 26.8 ± 5.7 kg/m2 and 86.0% female): 28 WBAT and 15 RWB. There were more interprosthetic fractures in the RWB group (p = 0.040). Mean follow-up was 3.8 years (range 1.0-10.4). Eight patients (18.6%) underwent reoperation. Kaplan-Meier analysis demonstrated no difference in 2-year survival between WBAT (80.6%, 95% CI 65.3-95.9) and RWB (83.3%, 95% CI 62.1-100.0; p = 0.54). Cox analysis showed increased reoperation risk with medial comminution (hazard ratio 10.7, 95% CI 1.5-80; p = 0.020) and decreased risk with anatomic reduction (hazard ratio 0.11, 95% CI 0.01-1.0; p = 0.046). Immediate weight-bearing did not significantly affect the risk of reoperation compared with RWB (relative risk 1.03, 95% CI 0.61-1.74; p = 0.91). CONCLUSIONS: LLP fixation failure was associated with medial comminution and non-anatomic reductions, not with postoperative weight-bearing. Medial comminution should be managed with additional fixation. Weight-bearing restrictions additional to this appear unnecessary and should be avoided.

Radiographic severity, extent and pattern of cartilage loss are not associated with patient reported outcomes before or after total knee arthroplasty in end-stage knee osteoarthritis.

BACKGROUND: The aim of this study was to determine if radiographic severity, extent or pattern of knee osteoarthritis was associated with pain and function before total knee arthroplasty (TKA) or improvement therein one year after TKA. METHODS: A prospective study of 259 patients undergoing unilateral TKA for Kellgren-Lawrence (KL) grade ≥ 3 knee osteoarthritis was conducted: mean age 69.8 ± 9.7 (44-91); mean BMI 31.0 ± 5.8 (17-52); 152/259 (58.7%) female. Preoperative radiographs were assessed using the KL and Ahlback systems. Preoperatively and 1 year postoperatively patients completed Oxford Knee Scores, VAS-Pain and EQ-5D scores. Full thickness cartilage loss was recorded intraoperatively. RESULTS: Median radiographic severity was Ahlback 2, KL 4: 51/259 (19.7%) hypertrophic; 23/259 (8.8%) atrophic. Neither Ahlback nor Kellgren-Lawrence OA grade was associated with OKS, VAS Pain or EQ-5D prior to TKA (p > 0.05). The extent and pattern of cartilage loss did not affect preoperative PROMs. Radiographic OA severity, compartment involvement, and pattern of cartilage loss were not significantly associated with PROMs or improvements therein following TKA (p > 0.05). Hypertrophic OA was associated with less pain before TKA (difference 6.8, 0.23-13.9 95%CI, p = 0.044), and worse improvement in OKS following TKA (difference -3.41, -6.8 to -0.05 95%CI, p = 0.047). Better preoperative OKS and hypertrophic OA were independently associated with poorer improvement in OKS 1 year following TKA (R2 = 0.208). CONCLUSION: Provided at least one compartment has KL grade ≥ 3 changes, further radiographic severity, pattern or extent of cartilage loss did not affect PROMs before or after TKA: multicompartmental was no worse than unicompartmental disease.

Management of low periprosthetic distal femoral fractures.

AIMS: Debate continues regarding the optimum management of periprosthetic distal femoral fractures (PDFFs). This study aims to determine which operative treatment is associated with the lowest perioperative morbidity and mortality when treating low (Su type II and III) PDFFs comparing lateral locking plate fixation (LLP-ORIF) or distal femoral arthroplasty (DFA). METHODS: This was a retrospective cohort study of 60 consecutive unilateral (PDFFs) of Su types II (40/60) and III (20/60) in patients aged ≥ 60 years: 33 underwent LLP-ORIF (mean age 81.3 years (SD 10.5), BMI 26.7 (SD 5.5); 29/33 female); and 27 underwent DFA (mean age 78.8 years (SD 8.3); BMI 26.7 (SD 6.6); 19/27 female). The primary outcome measure was reoperation. Secondary outcomes included perioperative complications, calculated blood loss, transfusion requirements, functional mobility status, length of acute hospital stay, discharge destination and mortality. Kaplan-Meier survival analysis was performed. Cox multivariate regression analysis was performed to identify risk factors for reoperation after LLP-ORIF. RESULTS: Follow-up was at mean 3.8 years (1.0 to 10.4). One-year mortality was 13% (8/60). Reoperation was more common following LLP-ORIF: 7/33 versus 0/27 (p = 0.008). Five-year survival for reoperation was significantly better following DFA; 100% compared to 70.8% (95% confidence interval (CI) 51.8% to 89.8%, p = 0.006). There was no difference for the endpoint mechanical failure (including radiological loosening); ORIF 74.5% (56.3 to 92.7), and DFA 78.2% (52.3 to 100, p = 0.182). Reoperation following LLP-ORIF was independently associated with medial comminution; hazard ratio (HR) 10.7 (1.45 to 79.5, p = 0.020). Anatomical reduction was protective against reoperation; HR 0.11 (0.013 to 0.96, p = 0.046). When inadequately fixed fractures were excluded, there was no difference in five-year survival for either reoperation (p = 0.156) or mechanical failure (p = 0.453). CONCLUSION: Absolute reoperation rates are higher following LLP fixation of low PDFFs compared to DFA. Where LLP-ORIF was well performed with augmentation of medial comminution, there was no difference in survival compared to DFA. Though necessary in very low fractures, DFA should be used with caution in patients with greater life expectancies due to the risk of longer term aseptic loosening. Cite this article: Bone Joint J 2021;103-B(4):635-643.

Profound reduction of ovarian estrogen by aromatase inhibition in obese women.

OBJECTIVE: It was hypothesized that aromatase inhibitor (AI)-induced interruption of estradiol negative feedback would modulate the reproductive hormone profile of obese women. METHODS: Regularly cycling women aged 18-40 years with a BMI of 18-25 kg/m(2) (normal weight, n = 10) or >30 kg/m(2) (obese; n = 12) were given AI daily for 7 days. Urinary hormone profiles were compared between groups. Fourteen eumenorrheic, normal weight women not receiving AI stimulation served as historical controls. Urinary metabolites for LH, FSH, estradiol (E1c), and progesterone (Pdg) were measured and normalized to a 28-day cycle. Serum estrone and estradiol were measured in the late follicular phase. RESULTS: Whole-cycle LH, FSH, and luteal Pdg excretion did not differ between obese (BMI = 37.1 + 7 kg/m(2) ) and normal weight women treated with AIs, although LH was greater in stimulated compared with unstimulated normal weight women. Whole cycle mean E1c was lower in AI-stimulated obese and normal weight participants compared with nonstimulated normal weight controls, but obese women treated with AI excreted far less E1c (467.7 ± 217.4 µg/mg Cr) than AI-treated normal weight women (911.4 ± 361.8 µg/mg Cr; P = 0.02). Follicular phase serum estrone and estradiol were also lower in AI-treated obese women versus AI-treated normal weight women (61.7 ± 22.8 and 18.3 ± 3.7 pg/ml versus 99.1 ± 30.5 and 37.7 ± 5.9 pg/ml, respectively; P = 0.034 and 0.005). CONCLUSIONS: Normal gonadotropin output and luteal function occur at the expense of reduced E1c excretion in AI-treated women, and this discrepancy is particularly evident in obese women.

Metabolic correlates of menopause: an update.

PURPOSE OF REVIEW: Metabolic syndrome (MetS) is a cluster of characteristics that increase the risk of cardiovascular disease and type 2 diabetes mellitus. We will review the most interesting and relevant studies on metabolic correlates of menopause published over the last year. RECENT FINDINGS: In the past year, studies have shifted focus from effects on cardiovascular disease and diabetes to effects of MetS on breast cancer as well as menopausal symptoms. Studies have found and further confirmed its negative effect on both breast cancer and menopausal symptoms. Focus has also been on treatment options including both lifestyle and pharmacologic. Recent studies also further investigate markers/predictors as well as genetic components influencing MetS development. SUMMARY: Over a quarter of the US population is affected by metabolic disease at midlife, and some studies have shown that the incidence of MetS increases with menopause. There are now more Americans who are age 65 and older than at any other time in US history. Thus, it is becoming ever more important to understand metabolic health, as well as the consequences of MetS.

Tumoral pseudoangiomatous stromal hyperplasia of the breast.

Tumoral pseudoangiomatous stromal hyperplasia (PASH) is a rare benign proliferative disease of the breast. The majority of the literature reports of PASH have not contained detailed descriptions of the imaging characteristics of PASH. A 10-year retrospective study of patients with tumoral PASH and a 20-year Ovid MEDLINE search were performed to determine whether specific imaging and needle biopsy results could characterize PASH preoperatively. We identified 22 patients with tumoral PASH. Seventeen (77%) of 22 women had a palpable lump and 14 (72%) of 21 had a density on mammography. Ultrasound (US) findings included mixed or hypoechoic echogenicity in 83 per cent and ill-defined borders in 62 per cent. Eight (36%) patients had lesions with a Breast Imaging Reporting and Data System (BI-RADS) classification of 4 or 5. The sensitivity of preoperative core needle biopsy (CNB) to identify PASH was 83 per cent. A review of the literature revealed that 90 per cent of patients with PASH had some malignant imaging characteristics and 95 per cent had a mass on mammography. The imaging characteristics of PASH exhibited marked variability. Excision of PASH after CNB may be considered for patients with symptoms, enlarging lesions, or lesions classified as BI-RADS 4 or 5. PASH diagnosed by CNB allows selected patients to avoid excision.

Clusters of transmembrane residues are critical for human prostacyclin receptor activation.

Relaxation of vascular smooth muscle and prevention of blood coagulation are mediated by ligand-induced activation of the human prostacyclin (hIP) receptor, a seven-transmembrane-domain G-protein-coupled receptor (GPCR). In this study, we elucidate the molecular requirements for receptor activation within the region of the ligand-binding pocket, identifying transmembrane residues affecting potency. Eleven of 30 mutated residues in the region of the ligand-binding domain exhibited defective activation (decreased potency). These critical residues localized to four distinct clusters (analysis via a rhodopsin-based human prostacyclin receptor homology model). Residues Y75(2.65) (TMII), F95(3.28) (TMIII), and R279(7.40) (TMVII) comprised the immediate binding-pocket cluster and were shown to be essential for proper receptor activation, compared to equivalent expression levels of the wild-type hIP (WT EC(50) = 1.2 +/- 0.1 nM; Y75(2.65)A EC(50) = 347.3 +/- 62.8 nM, p < 0.001; F95(3.28)A EC(50) = 8.0 +/- 0.6 nM, p < 0.001; R279(7.40)A EC(50) = 130 +/- 63.0 nM, p < 0.001). Residues S20(1.39) (TMI), F24(1.43) (TMI), and F72(2.62) (TMII) were localized to a cluster involving P17(1.36), a critical residue thought to facilitate transmembrane movement during changes in activation conformation. A third cluster formed around amino acid D60(2.50) (TMII), containing the highly conserved (100% of prostanoid receptors) D288(7.49)/P289(7.50) motif located in TMVII. Last, a large hydrophobic cluster composed of aromatic residues F146(4.52) (TMIV), F150(4.56) (TMIV), F184(5.40) (TMV), and Y188(5.44) (TMV) was observed away from the ligand-binding pocket, but still necessary for hIP activation. These results assist in delineating the potential molecular requirements for agonist-induced signaling through the transmembrane domain. Such observations may be generally applicable, as many of these clusters are highly conserved among the prostanoid receptors as well as other class A GPCRs.