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BACKGROUND We aimed to determine risk factors for incident CKD in a large population-based cohort. METHODS This prospective opt-in population-based cohort study is based on the 45 and Up Study, where New South Wales residents aged ≥45 years were randomly sampled from the Services Australia enrolment database and agreed to complete the 45 and Up Study baseline questionnaire and have their responses linked to their health data in routinely-collected databases. The primary outcome was the development of incident CKD, defined as eGFR

Background: Commercially available wrist-mounted exercise monitors may offer objective data on disease and recovery. This study is the first to evaluate the potential of such devices in the assessment of frozen shoulder and the effects of treatment. Methods: Twenty-one patients with isolated, unilateral frozen shoulder wore a wrist-mounted accelerometer (Fitbit Fire II, Fitbit Inc. 2007, California, USA) on each wrist for two separate seven-day periods, one week before and six months after treatment. The monitors produced an activity count for each 24-hour period, accounting for all movements of the upper limb. Three values were calculated for each time period: (1) the mean activity count for each limb, (2) the total activity count for both limbs, and (3) an activity count ratio calculated by dividing the activity of the frozen limb by the unaffected limb. Constant score, American Shoulder and Elbow Surgeons, visual analog scale–pain, and range of movement were recorded before and after treatment. Results: Mean activity counts were significantly lower in the frozen shoulder limb than those in the unaffected limb over the initial seven-day period (6066 vs. 7516; P = .04). The activity count ratio significantly improved after treatment (0.83 vs. 096; p 0.01), whereas the mean total activity count remained similar before and after treatment (14915 vs. 12371; P = .18), demonstrating that activity transferred from the unaffected limb back to the previously frozen limb. Range of movement (P

Purpose To evaluate the long-term effect of subthreshold nanosecond laser (SNL) treatment on progression to late age-related macular degeneration (AMD). Design Observational extension study of a randomized, sham-controlled trial. Participants Two hundred twelve participants with bilateral large drusen. Methods The Laser Intervention in the Early Stages of AMD (LEAD) study was a 36-month trial where participants were randomized to receive SNL or sham treatment in 1 eye at 6-monthly intervals up to 30 months. After the completion of the LEAD study, the 2 largest recruiting sites offered remaining participants an opportunity to enroll in a 24-month observational extension study. This study thus examined all participants from these 2 sites who were enrolled in the LEAD study at baseline, including the additional observational data. Main Outcome Measures Time to develop late AMD, defined on multimodal imaging, between those randomized the SNL or sham treatment. Results Overall, no significant difference was found in the rate of progression over a 60-month period in those randomized to the SNL compared with the sham group (adjusted hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.36–1.09; P = 0.098), similar to the findings at 36 months in the LEAD Study. However, evidence of treatment effect modification continued to emerge based on the coexistence of reticular pseudodrusen (RPD; P = 0.007, adjusted interaction). Namely, progression was slowed significantly with SNL treatment for those without coexistent RPD (adjusted HR, 0.34; 95% CI, 0.16–0.71; P = 0.004), but it was not significantly different for those with RPD (adjusted HR, 1.81; 95% CI, 0.67–4.88; P = 0.239). Conclusions A 24-month observational extension study to the LEAD Study confirmed that SNL treatment did not significantly reduce the overall rate of progression to late AMD in a cohort with intermediate AMD. However, the persistence of a potential beneficial treatment effect in those without coexistent RPD over a longer follow-up duration of an additional 24 months without additional treatment is encouraging. These findings provide further justification for future trials to examine the potential value of SNL treatment for slowing progression in intermediate AMD.

INTRODUCTION Periprosthetic femoral fractures are an increasingly common post-operative complication of total hip arthroplasty (THA). Though varus malalignment is known to increase fracture risk in standard-length femoral stems, varus malalignment is not as well studied in short stems. Therefore, the purpose of this study was to determine if varus malalignment contributes to early periprosthetic fracture risk in a cementless taper-wedged, short femoral stem. MATERIALS AND METHODS This retrospective review included 366 consecutive patients (441 THAs) having undergone THA via anterior approach by a single surgeon between July 2014 and December 2016. All patients received the same short, cementless femoral stem. Femoral component angle was measured on 6-week post-THA weight-bearing radiographs, with malalignment defined as a femoral component angle exceeding 0° ± 3°. Periprosthetic femoral fracture and aseptic loosening occurring within 2 years post-THA were recorded. RESULTS The final data analysis included 426 hips with a mean follow-up time of 32.9 ± 10.2 months. Varus and neutral alignment occurred in 84 (19.6%) and 342 (79.9%) of stems, respectively. Three (0.7%) periprosthetic femoral fractures occurred within 2 years, all occurring in patients with neutrally aligned femoral stems. One (0.2%) stem failed due to aseptic loosening and was malaligned. CONCLUSION Despite nearly 20% of stems placed in varus alignment, three of the four early complications occurred in a neutrally aligned stem. Based on these results, forceful intraoperative realignment of a short femoral stem with good initial fixation may present an unnecessary increased risk of intraoperative fracture.

Objectives/hypothesis Radiation-associated sarcomas of the head and neck (RASHN) are known but rare sequelae after radiation for squamous cell carcinoma. The purpose of this study was to characterize RASHN, estimate the risk of RASHN in head and neck squamous cell patients after therapeutic radiation, and compare their survival to that of patients with de novo sarcomas of the head and neck (dnSHN). Study design Retrospective database analysis. Methods RASHN and dnSHN cases were collected from the Surveillance, Epidemiology, and End Results Database to identify risk factors and calculate incidence and latency. Survival was compared between RASHN and dnSHN. Results The risk of RASHN was 20.0 per 100,000 person-years. The average latency period was 124.2 months (range 38-329). The cumulative incidence of RASHN at 20 years was 0.13%. Oral cavity and oropharynx primaries demonstrate increased risk. Five-year overall survival of RASHN was 22.4% compared to 64.5% for dnSHN. Conclusions RASHN are confirmed to be rare. RASHN have poor overall survival and worse survival compared to dnSHN. The impact of intensity-modulated radiation therapy protocols on this risk is unknown. Modifiable risk factors of smoking and alcohol consumption continue to dwarf radiation therapy as risk factors of second primary head and neck cancers. Level of evidence 3 Laryngoscope, 2021.

BACKGROUND Translabyrinthine approaches (TLAs) for resection of skull base neoplasms are complex with variable reconstruction techniques. Fat grafts in conjunction with hydroxyapatite bone cement techniques have seldom been described in terms of possible superiority to other skull base reconstruction techniques. We sought to determine the impact of this skull base reconstruction technique on clinical outcomes and patient's satisfaction. METHOD We performed a retrospective analysis of all patients who underwent translabyrinthine approaches for resection of CPA lesions over a 5-year period. Both post-op objective and subjective markers of reconstruction, as well as postoperative complications, were collected and analyzed. RESULTS Sixty-nine patients were included, 34 underwent reconstruction with hydroxyapatite and fat (rHAC) and 35 with fat alone (rF). rHAC was associated with fewer cranial wound superficial infection/dehiscence (0% vs 14.3%; p = 0.029) and shorter length of stay (mean ± standard deviation) (6.9 ± 7.4 vs 4.4 ± 3.7 days, p = 0.008). Postoperative subjective characterization of rHAC demonstrated improved satisfaction scores (1.38 ± 0.5 vs 1.83 ± 1; p = 0.049) and fewer reports of post-operative irregularities (11.5% vs 37.5%; p = 0.017). CONCLUSION The use of hydroxyapatite for cranial reconstruction after translabyrinthine approaches has improved patient satisfaction and decreased cranial defects in our small series. Postoperative complications are consistent with other described methods, but with shorter hospital stay, decreased risk of superficial wound dehiscence/infection, and a perceived superiority in preventing percutaneous post-op CSF leaks.

As SARS-CoV-2 vaccines have started to be rolled out, a key question facing transplant units has been whether listing for transplantation should be contingent on recipients having received a vaccine. We aimed to provide an ethical framework when considering potential transplant candidates who decline vaccination. We convened a working group comprising transplant professionals, lay members and patients and undertook a literature review and consensus process. This group's work was also informed by discussions in two hospital clinical ethics committees. We have reviewed arguments for and against mandating vaccination prior to listing for kidney transplantation and considered some practical difficulties which may be associated with a policy of mandated vaccination. Rather than requiring that all patients must receive the SARS-CoV-2 vaccine prior to transplant listing, we recommend considering vaccination status as one of a number of SARS-CoV-2-related risk factors in relation to transplant listing. Transplant units should engage in individualised risk-benefit discussions with patients, avoid the language of mandated treatments and strongly encourage uptake of the vaccine in all patient groups, using tailor-made educational initiatives.

Objectives To investigate trends of osteoporosis treatment rates, and factors affecting osteoporosis treatment after hip fracture admission within a single health care system in Hawaii. Methods A retrospective chart review was conducted of patients aged 50 years or older and hospitalized for hip fractures between January 1, 2011 and December 31, 2019 at Hawaii Pacific Health, a large health care system in Hawaii. We collected data on basic demographics and osteoporosis medication prescription from electronic medical records. We evaluated trends of osteoporosis treatment rates and performed logistic regression to determine factors associated with osteoporosis treatment. Results The mean for treatment rates for osteoporosis from 2011 to 2019 was 17.2% (range 8.8%-26.0%). From 2011 to 2019 there was a small increase in treatment rates from 16.3% in 2011 to 24.1% in 2019. Men were less likely to receive osteoporosis treatment after admission for hip fracture. Patients discharged to a facility were more likely to receive osteoporosis treatment. As compared to women, men who had a hip fracture were less likely to receive dual-energy X-ray absorptiometry scan, and osteoporosis medication before hip fracture admission. Conclusions The use of osteoporosis medication for secondary prevention after admission for hip fracture in Hawaii from 2011 to 2019 was low. However, there was a small increase in treatment rates from 2011 to 2019. Disparities in treatment of osteoporosis after hip fracture were noted in men. Significant work is needed to increase treatment rates further, and to address the disparity in osteoporosis treatment between men and women.

The most effective option for gastric cancer risk management in individuals with a CDH1 germline pathogenic or likely pathogenic variant (PV) in Australia is prophylactic total gastrectomy (PTG). There is, however, increasing confidence in endoscopic surveillance as a risk management strategy thus affording individuals with a CDH1 PV with challenging decisions regarding their gastric cancer risk management. For young people, this decision-making comes at a complex development stage of emerging and young adulthood. This study aims to explore the factors that influence young people's decision-making about their gastric cancer risk management due to a CDH1 PV. Potential participants were identified and approached through the Parkville Familial Cancer Centre in Melbourne, Australia. Thematic analysis was used to interpret and analyze the data. Qualitative interviews were conducted with 13 people with a CDH1 PV aged 18 to 39 years, inclusive. The interviews found that participants' familial and shared experiences of cancer and risk management, perceived tolerance of uncertainty, and desire for control over their cancer risk were fundamental in their decision-making about their gastric cancer risk management. The participants' young adult life stage was also deemed particularly important in decisions about the timing of PTG. The findings of this study are vital to inform decisional counseling discussions with this unique population.

OBJECTIVE To determine the influence extent of resection and tumor characteristics on facial nerve (FN) outcomes following microsurgical resection of vestibular schwannoma (VS). STUDY DESIGN Retrospective chart review. SETTING Tertiary referral center. PATIENTS Three hundred eighty-five patients who underwent VS microsurgical resection. INTERVENTIONS Microsurgical VS resection. MAIN OUTCOME MEASURES House-Brackmann (HB) scores postoperatively. Good FN function was defined as HB grade I and II and poor FN function was defined as HB grade III and VI. Gross total resection (GTR) versus subtotal resection (STR). Propensity-score matching was used in subset analysis to balance tumor volume between the surgical cohorts, followed by multivariable analysis. RESULTS Seventy-one patients (18%) underwent STR and 314 patients (82%) underwent GTR. Two hundred fourteen patients (63%) had good FN function at 2 to 3 weeks postoperatively, and 80% had good FN function at 1 year. In single predictor analysis, STR did not influence FN function at 2 to 3 weeks (p = 0.65). In propensity-score matched subset analysis (N = 178), patients with STR were less likely to have poor FN function at 2 to 3 weeks (p = 0.02) independent of tumor volume (p = 0.004), but there was no correlation between STR and FN function at 1 year (p = 0.09). Ventral extension of tumor relative to the internal auditory canal plane was associated with poor FN outcomes at 2 to 3 weeks (p = 0.0001) and 1-year postop (p = 0.002). CONCLUSIONS When accounting for tumor volume, STR is protective in immediate postoperative FN function compared to GTR. Ventral extension of the tumor is a clinical predictor of long-term FN outcomes.

Hematoma formation and the need for blood transfusions are commonly reported complications after shoulder arthroplasty. Tranexamic acid (TXA) has been widely used in hip and knee arthroplasty to decrease perioperative blood loss. The role of TXA is still being established in shoulder arthroplasty.We conducted a double-blind randomized controlled trial comparing intravenous TXA vs. placebo in 60 patients undergoing primary anatomic or reverse shoulder arthroplasty. Of these patients, 29 received a placebo whereas 31 received a single dose of 2 g of intravenous TXA. Patient demographic characteristics, as well as drain tube output, blood loss, hematoma formation, transfusion requirement, length of hospital stay, and pain score, were recorded. Patients were followed up for 12 weeks to assess for complications.Patients who received TXA had a lower drain tube output at all time points: 41 mL vs. 133 mL at 6 hours, 75 mL vs. 179 mL at 12 hours, and 94 mL vs. 226 mL at 24 hours (P.001 for all). They also had a higher postoperative hemoglobin (Hb) level (12.3 g/dL vs. 11.4 g/dL, P = .009), lower change in Hb level (1.7 g/dL vs. 2.3 g/dL, P = .011), lower total Hb loss (0.078 g vs. 0.103 g, P = .042), lower blood volume loss (0.55 L vs. 0.74 L, P = .021), higher postoperative hematocrit level (36.7% vs. 34.6%, P = .020), and lower hematocrit change (5.4% vs. 7.6%, P = .022). There was no significant difference in pain score or length of hospital stay, and no patients required a transfusion.A single dose of 2 g of intravenous TXA decreases blood loss and drain tube output in primary anatomic and reverse arthroplasty of the shoulder. No differences were detected in the occurrence of complications, need for transfusion, pain score, or length of hospital stay. With the mounting evidence now available, patients undergoing elective primary shoulder arthroplasty should be given intravenous TXA to decrease perioperative blood loss.

Periprosthetic fractures around a total knee arthroplasty (TKA), comminuted and intra-articular femur fractures, or fracture nonunions in osteoporotic bone represent technically challenging problems. This is particularly true when the fracture involves a loose femoral component or the pattern results in suboptimal fixation potential. These clinical indications often arise in an older and comorbid patient population in whom a principal goal of treatment includes allowing for early mobilization. Limited data indicate that arthroplasty via distal femoral replacement (DFR) is a reasonable alternative to open reduction and internal fixation, allowing for early ambulation with low complication rates. We performed a retrospective review of trauma and arthroplasty surgeries at three tertiary referral institutions. Adult patients treated for the above with a DFR were included. Patients with active infection, open and/or high-energy injuries and revisions unrelated to fracture were excluded. Patient demographics, treatment details, and outcomes were assessed. Between 2002 and 2017, 90 DFR's were performed for the above indications with a mean follow-up of 24 months. Postoperatively, 80 patients (88%) were allowed to weight bear as tolerated, and at final follow-up, 9 patients (10%) remained dependent on a wheelchair. The average arc of motion at final follow-up was 95 degrees. There were seven (8%) implant-related complications requiring secondary surgeries: two infections, one with associated component loosening; one fracture of the hinge mechanism and one femoral component failure in conjunction with a patellofemoral dislocation (both requiring revision); one case of patellofemoral arthrosis in a patient with an unresurfaced patella; one periprosthetic fracture with associated wound dehiscence; and one case of arthrofibrosis. In each of these cases, only modular components of the DFR were exchanged. All nonmodular components cemented into the femur or tibia were retained. DFR provides a viable reconstruction option in the treatment of acute distal femur fractures, periprosthetic femur fractures, and fracture nonunions. We noted that in an elderly patient population with high comorbidities, the complication and secondary surgery rates remained relatively low, while allowing for immediate weight bearing.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals working with cancer survivors to ensure that each survivor’s complex and varied needs are addressed. The Guidelines provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment; recommendations to help promote healthful lifestyle behaviors, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes the recommendations regarding employment and return to work for cancer survivors that were added in the 2021 version of the NCCN Guidelines.

Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease. Autoimmune processes have been hypothesized to contribute to disease progression; however, the presence of autoantibodies in the serum has been variable. Given that COPD is a lung disease, we sought to investigate whether autoantibodies in sputum supernatant would better define pulmonary autoimmune processes. Matched sputum and serum samples were obtained from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study and at the Guangzhou Institute of Respiratory Health (GIRH). Samples were collected from patients with varying severity of COPD, asymptomatic smokers, and healthy control subjects. IgG and IgM autoantibodies were detected in sputum and serum of all subjects in both cohorts using a broad-spectrum autoantigen array. No differences were observed in sputum autoantibodies between COPD and asymptomatic smokers in either cohort. In contrast, 16% of detectable sputum IgG autoantibodies were decreased in subjects with COPD compared to healthy controls in the ADEPT cohort. Compared to asymptomatic smokers, approximately 13% of detectable serum IgG and 40% of detectable serum IgM autoantibodies were differentially expressed in GIRH COPD subjects. Of the differentially expressed specificities, anti-nuclear autoantibodies were predominately decreased. A weak correlation between increased serum IgM anti-tissue autoantibodies and a measure of airspace enlargement was observed. The differential expression of specificities varied between the cohorts. In closing, using a comprehensive autoantibody array, we demonstrate that autoantibodies are present in subjects with COPD, asymptomatic smokers, and healthy controls. Cohorts displayed high levels of heterogeneity, precluding the utilization of autoantibodies for diagnostic purposes.

PURPOSE: The association between patient-reported experience of care and care quality is not well described. The purpose of this study was to assess the relationship between the patient-reported experience and receipt of guideline-concordant colon cancer (CC) treatment. METHODS: Medicare beneficiaries with resected stage I-III CC (2003-2013) were identified in the linked SEER Consumer Assessment of Healthcare Providers and Systems data set. Patient-reported scores were compared by receipt of guideline concordant care (GCC) (resection of ≥ 12 lymph nodes [stage I-III] and adjuvant chemotherapy [stage III]). Linear mixed-effects regression was performed to compare adjusted mean patient experience scores by GCC. RESULTS: Of the 1,010 identified patients, 58.4% of stage I (n = 192/329) and 73.4% of stage II (n = 298/406) patients underwent resection of ≥ 12 LN. Among stage III patients, 76.0% (n = 209/275) underwent resection of ≥ 12 lymph node and 52.4% (n = 144/275) received adjuvant chemotherapy. By multivariable analysis, patient-reported scores of healthcare quality, physicians, physician communication, getting needed care, and getting care quickly were similar among patients who received GCC compared with those who did not. However, mean scores of overall healthcare quality (91.3 v 82.4, P = .0004) and getting needed care (92.8 v 86.8, P = .047) were higher among stage III patients who received GCC compared with those who did not. CONCLUSION: Patient-reported scores of healthcare quality and ability to get needed care are associated with GCC among elderly patients with stage III CC. Further investigation is needed to determine whether patient-reported experience correlates with other clinical measures of quality of CC care.

This article reviews the contemporary diagnosis and management of the most common abdominal neoplasms and cystic lesions diagnosed in the fetus. Fetal tumors discussed include teratomas (sacrococcygeal, cervical or mediastinal), mesoblastic nephroma, nephroblastoma (Wilms’ tumor), neuroblastoma, and hepatoblastoma. Fetal abdominal cystic lesions discussed include ovarian cyst, choledochal cyst, intestinal duplication cyst, mesenteric cyst, simple hepatic cyst, and meconium pseudocyst. We discuss the rare indications for fetal intervention or fetal surgery and other perinatal management, including prenatal interventions and fetal surgery for sacrococcygeal teratoma. The lesions reviewed are detected by widespread use of screening ultrasonography during pregnancy. Work-up for these abnormalities may include fetal MRI which enhances the diagnostic accuracy of abdominal tumors and cystic lesions and can aid in characterization of the lesion in relationship to surrounding anatomic structures. Accurate prenatal diagnosis of such lesions permits recommendations for optimal location and timing of delivery, and inclusion of appropriate caregivers and expertise to facilitate postnatal management. Perinatal management of the fetus with a neoplasm requires consideration of the optimal timing and mode of delivery, and pediatric oncology and surgical specialty care. The majority of tumors diagnosed antenatally have good prognosis with current multimodality treatment.

Background End stage kidney disease (ESKD) is associated with many losses, subsequently impacting mental wellbeing. Few studies have investigated the efficacy of psychosocial interventions for people with ESKD and none exist for Indigenous people, a population in which the ESKD burden is especially high. Methods This three-arm, waitlist, single-blind randomised controlled trial examined efficacy of the Stay Strong App in improving psychological distress (Kessler distress scale; K10), depressive symptoms (adapted Patient Health Questionnaire; PHQ-9), quality of life (EuroQoL; EQ. 5D) and dialysis adherence among Indigenous Australians undergoing haemodialysis in central and northern Australia (Alice Springs and Darwin), with follow up over two 3-month periods. Effects of immediate AIMhi Stay Strong App treatment were compared with those from a contact control app (The Hep B Story) and treatment as usual (TAU). Control conditions received the Stay Strong intervention after 3 months. Results Primary analyses of the full sample (N = 156) showed statistically significant decreases in K10 and PHQ-9 scores at 3 months for the Hep B Story but not for the Stay Strong app or TAU. Restricting the sample to those with moderate to severe symptoms of distress or depression (K10 > =25 or PHQ-9 > =10) showed significant decreases in K10 and PHQ-9 scores for both Stay Strong and Hep B Story. No significant differences were observed for the EQ-5D or dialysis attendance. Conclusions Findings suggest that talking to people about their wellbeing and providing information relevant to kidney health using culturally adapted, locally relevant apps improve the wellbeing of people on dialysis. Further research is required to replicate these findings and identify active intervention components. Trial registration ACTRN12617000249358; 17/02/2017.

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

Purpose Privately insured patients with head and neck cancer (HNC) typically have better outcomes; however, differential outcome among Medicaid versus the uninsured is unclear. We aimed to describe outcome disparities among HNC patients uninsured versus on Medicaid. Methods A cohort of 18-64-year-old adults (n = 57 920) with index HNC from the Surveillance, Epidemiology, and End Results 18 database (2007-2015) was analyzed using Fine and Gray multivariable competing risks proportional hazards models for HNC-specific mortality. Results Medicaid (sdHR = 1.65, 95% CI 1.58, 1.72) and uninsured patients (sdHR = 1.55, 95% CI 1.46, 1.65) had significantly greater mortality hazard than non-Medicaid patients. Medicaid patients had increased HNC mortality hazard than those uninsured. Conclusion Compared with those uninsured, HNC patients on Medicaid did not have superior survival, suggesting that there may be underlying mechanisms/factors inherent in this patient population that could undermine access to care benefits from being on Medicaid.

There is significant uncertainty about the potential role of temperature control in the intensive care unit (ICU) in general, but more specifically in septic shock patients.1,2 Common techniques for temperature control have been limited by minimal effect (eg, paracetamol, fans or air blankets), undesirable side effects (eg, non-steroidal anti-inflammatories), or being burdensome (eg, heavy sedation, paralysis with surface cooling; intravascular cooling devices3). In contrast, the potential of newer-generation surface-cooling devices to achieve temperature control more simply has created the possibility of studying temperature modulation in the septic ICU population.

Objective To examine whether diabetes shared medical appointments (SMAs) implemented as part of usual clinical practice in diverse health systems are more effective than usual care in improving and sustaining A1c improvements. Research Design and Methods A multi-site cluster randomized pragmatic trial examining implementation in clinical practice of diabetes SMAs in five Veterans Affairs (VA) health systems was conducted from 2016 to 2020 among 1537 adults with type 2 diabetes and elevated A1cs. Eligible patients were randomly assigned to either: (1) invitation to participate in a series of SMAs totaling 8–9 h; or (2) continuation of usual care. Relative change in A1c (primary outcome) and in systolic blood pressure, insulin starts, statin starts, and anti-hypertensive medication classes (secondary outcomes) were measured as part of usual clinical care at baseline, at 6 months and at 12 months (~7 months after conclusion of the final SMA in four of five sites). We examined outcomes in three samples of SMA participants: all those scheduled for a SMA, those attending at least one SMA, and those attending at least half of SMAs. Results Baseline mean A1c was 9.0%. Participants scheduled for an SMA achieved A1c reductions 0.35% points greater than the control group between baseline and 6-months follow up (p = .001). Those who attended at least one SMA achieved reductions 0.42 % points greater (p p < .001) than the control group. At 12-month follow-up, the three SMA analysis samples achieved reductions from baseline ranging from 0.16 % points (p = 0.12) to 0.29 % points (p = .06) greater than the control group. Conclusions Diabetes SMAs as implemented in real-life diverse clinical practices improve glycemic control more than usual care immediately after the SMAs, but relative gains are not maintained. Our findings suggest the need for further study of whether a longer term SMA model or other follow-up strategies would sustain relative clinical improvements associated with this intervention. Trial Registration ClinicalTrials.gov ID NCT02132676

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease. Recommendations for disease monitoring and treatment of recurrent disease are also included. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. This article summarizes the panel’s discussions for the 2021 update of the guidelines with regard to systemic therapy for metastatic castration-resistant prostate cancer.

Management of small vestibular schwannomas (VSs) remains controversial. When surgery is chosen, the preservation of facial and cochlear nerve function is a priority. In this report, we introduce and evaluate a technique to anatomically preserve the vestibular nerves to minimize manipulation and preserve the function of the facial and cochlear nerves. The vestibular nerve preservation technique was prospectively applied to resect small VS tumors in patients with serviceable preoperative hearing (American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A or B). Clinical and radiological data were recorded and analyzed. Ten patients met the inclusion criteria. The mean (SD) age was 40.4 (12.5) years. Follow-up ranged from 6 weeks to 2 years. The maximum tumor diameter parallel to the internal auditory canal ranged from 10 to 20 mm (mean, 14.9 (3.1) mm). There were three Koos grade 3 and seven Koos grade 2 tumors. Gross total resection was achieved in all cases. Both the facial and cochlear nerves were anatomically preserved in all cases. Postoperatively, 7 patients (70%) remained in the AAO-HNS class A or B hearing category. None of the patients had new vestibular symptoms, and all had House–Brackmann grade 1 facial function. Nervus intermedius dysfunction was observed in 1 patient preoperatively, which worsened postoperatively. Two patients had new nervus intermedius symptoms postoperatively. Improvement of facial nerve and hearing outcomes is feasible through the intentional preservation of the vestibular nerves in the resection of small VSs. Longer follow-up is required to rule out tumor recurrence.

Objective There are no direct comparisons between the success of collagen allografts versus traditional autografts for tympanic membrane (TM) repair. We sought to compare success rates in a large series of patients undergoing tympanoplasty using collagen allografts versus autologous tissues. Study design Retrospective review. Setting Academic medical center. Subjects and methods Single institution retrospective chart review was performed for adult subjects with TM perforation undergoing tympanoplasty. Demographic, clinical, and surgical data were collected. Statistical analysis was completed using Rstudio. Each factor was examined to assess effect on graft success rate using logistic regression. Results Two hundred sixty-five surgeries met criteria with four main grafting materials or combinations thereof. The overall graft success rate was 81.1% with failure rate of 18.9%. There was no significant association between failure rates and: age, sex, perforation cause, size, and location, primary or revision status, middle ear status (wet or dry), concomitant procedures (mastoidectomy or ossiculoplasty), presence of active cholesteatoma, or surgical technique. Although not statistically significant, the odds of success for perichondrium + cartilage were 7.5 times higher than collagen allografts (p = 0.07, 95% confidence interval [CI] = 0.81-69.6). The odds of success for the postauricular (odds ratio [OR] = 6.4) and transcanal approaches (OR = 24.8) were significantly greater than for endaural (p = 0.007 and p = 0.008, respectively). Conclusion In tympanoplasty surgeries performed on patients with TM perforation, we found no statistically significant difference in graft failure rates between collagen allograft and other grafting materials or combinations, though the higher odds ratio of success with cartilage + perichondrium may be clinically relevant.

Background Determination of risks for chronic kidney disease (CKD) progression could improve strategies to reduce progression to ESKD. The eGFR Study recruited a cohort of adult Aboriginal and Torres Strait Islander people (Indigenous Australians) from Northern Queensland, Northern Territory and Western Australia, aiming to address the heavy CKD burden experienced within these communities. Methods Using data from the eGFR study, we explored the association of baseline liver function tests (LFTs) (alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin and albumin) and full blood count (FBC) indices (white blood cell and red blood cell counts and haemoglobin) with annual eGFR decline and renal outcomes (first of 30% decline in eGFR with a follow-up eGFR 2, initiation of renal replacement therapy, or renal death). Comparisons of baseline variables across eGFR categories were calculated using analysis of variance and logistic regression as appropriate. Linear and multivariable regression models were used to estimate the annual change in eGFR for changes in FBC indices and LFTs. Cox proportional hazard models were used to estimate the hazard ratio for developing renal outcome for changes in baseline FBC indices and LFTs. Results Of 547 participants, 540 had at least one baseline measure of LFTs and FBC indices. The mean age was 46.1 (14.7) years and 63.6% were female. The median follow-up was 3.1 (IQR 2.8–3.6) years. Annual decline in eGFR was associated with low serum albumin (p p = 0.007). After adjustment for age, gender, urine albumin/creatinine ratio, diabetes, BMI, CRP, WHR, alcohol consumption, cholesterol and triglycerides, low serum albumin (p p = 0.012) and bilirubin (p = 0.011) were associated with annual decline in eGFR. Renal outcomes were inversely associated with serum albumin (p Conclusions GGT, ALP, bilirubin, albumin and haemoglobin independently associate with renal outcomes. Contrary to findings from other studies, no association was found between renal outcomes and other FBC indices. These findings may help focus strategies to prevent disease progression in this high-risk population.

Aboriginal and Torres Strait Islander Australians (Indigenous Australians) suffer some of the highest rates of chronic kidney disease (CKD) in the world. Among Indigenous Australians in remote areas of the Northern Territory, prevalence rates for renal replacement therapy (RRT) are up to 30 times higher than national prevalence. Anemia among patients with CKD is a common complication. Iron deficiency is one of the major causes. Iron deficiency is also one of the key causes of poor response to the mainstay of anemia therapy with erythropoiesis-stimulating agents (ESAs). Therefore, the effective management of anemia in people with CKD is largely dependent on effective identification and correction of iron deficiency. The current identification of iron deficiency in routine clinical practice is dependent on 2 surrogate markers of iron status: serum ferritin concentration and transferrin saturation (TSAT). However, questions exist regarding the use of serum ferritin concentration in people with CKD because it is an acute-phase reactant that can be raised in the context of acute and chronic inflammation. Serum ferritin concentration among Indigenous Australians receiving RRT is often markedly elevated and falls outside reference ranges within most national and international guidelines for iron therapy for people with CKD. This review explores published data on the challenges of managing anemia in Indigenous people with CKD and the need for future research on the efficacy and safety of treatment of anemia of CKD in patients with high ferritin and evidence iron deficiency.

Background Unicompartmental knee arthroplasty (UKA) demonstrates excellent functional outcomes and patient satisfaction with low complication rates for single compartment knee arthritis. For patients with bilateral symptoms, single-stage bilateral UKA (SSBUKA) provides an alternative to staged procedures but may risk increased blood loss and systemic complications. Therefore, the purpose of this study is to compare 90-day postoperative complications between unilateral UKA and SSBUKA without exclusion for comorbidities. Methods A retrospective review was completed for 555 consecutive patients having undergone UKA (317 unilateral and 238 bilateral). Data collection included patient demographics and 90-day complications. Independent t-tests (continuous) and Fishers' Exact tests (nominal) were performed to determine differences between unilateral UKA and SSBUKA patients. Results The SSBUKA group had more male patients than the unilateral group (51.3% and 43.8%, respectively). There was no difference in age, body mass index or comorbidity classification. More SSBUKA patients experienced nausea than unilateral patients (17.6% and 11.0%), however, no significant differences were observed in the overall incidence of wound or systemic complications, and no transfusions were required. Significantly more unilateral patients (96.2%) were discharged home compared to SSBUKA (63.0%) (p Conclusions SSBUKA did not increase the risk of early postoperative systemic or wound complications, when performed in all patients with symptomatic disease without exclusion criteria as compared to patients undergoing unilateral UKA. Therefore, SSBUKA can safely be performed on the majority of patients who present to experienced high volume community hospitals.

Background Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimat...

Background Obstructive sleep apnea is a highly prevalent disorder often treated with continuous positive airway pressure (CPAP). CPAP transmits high pressures through the Eustachian tube, and has significant implications for patients undergoing surgery of the middle ear, inner ear, and lateral skull base. In such patients, nothing is known regarding the likelihood of surgical complications with CPAP use, or medical complications with its cessation. No consensus or guidelines exist for postoperative management of this vitally important but potentially hazardous therapy. Objective To gain an understanding of the current state of practice with regards to postoperative CPAP management in patients undergoing middle ear, stapes, cochlear implant, and lateral skull base surgeries. Methods An electronic survey was sent to all members of the American Neurotology Society via email. Results The survey was completed by 54 neurotologists. Duration of postoperative CPAP limitation had similar distribution for surgery of the middle ear, stapes, and skull base: fewer surgeons recommend immediate use, with more advising ≤1 week and ≥2 week abstinence. For cochlear implantation, immediate use is most commonly advocated. The rationale for restricting postoperative CPAP use varied by surgery type. Subgroup analysis showed no variations by region; however, surgeons with >15 years of experience tend to advocate for earlier return to CPAP than those with less experience. Conclusion Current neurotology practice varies widely concerning CPAP management after otologic and neurotologic surgeries, both with regard to duration of CPAP abstinence and in rationale for its limitation.

BACKGROUND Ventricular tachycardia (V-tach) is the most common lethal arrhythmia, yet 90% of alarms are false and contribute to alarm fatigue. We hypothesize that some true V-tach also causes alarm fatigue because current criteria are too sensitive (i.e., ≥6 beats ≥100 beats/min [bpm]). PURPOSE This study was designed to determine (1) the proportion of clinically actionable true V-tach events; (2) whether true actionable versus nonactionable V-tach differs in terms of heart rate and/or duration (seconds); and (3) if actionable V-tach is associated with adverse outcomes. METHODS This was a secondary analysis in 460 intensive care unit (ICU) patients. Electronic health records were examined to determine if a V-tach event was actionable or nonactionable. Actionable V-tach was defined if a clinical action(s) was taken within 15 minutes of its occurrence (i.e., new and/or change of medication, defibrillation, and/or laboratory test). Maximal heart rate and duration for each V-tach event were measured from bedside monitor electrocardiography. Adverse patient outcomes included a code blue event and/or death. RESULTS In 460 ICU patients, 50 (11%) had 151 true V-tach events (range 1-20). Of the 50 patients, 40 (80%) had only nonactionable V-tach (97 events); 3 (6%) had both actionable and nonactionable V-tach (32 events); and 7 patients (14%) had only actionable V-tach (23 events). There were differences in duration comparing actionable versus nonactionable V-tach (mean 56.19 ± 116.87 seconds vs. 4.28 ± 4.09 seconds; P = 0.001) and maximal heart rate (188.81 ± 116.83 bpm vs. 150.79 ± 28.26 bpm; P = 0.001). Of the 50 patients, 3 (6%) had a code blue, 2 died, and all were in the actionable V-tach group. CONCLUSIONS In our sample

A pelvic mass in a common condition and a thorough history and examination is important to identify possible causes. A combination of laboratory investigations and radiological imaging is helpful to reach a diagnosis and also triage cases of malignancy. In this review we consider common presentations, methods to assess the risk of malignancy and treatment strategies of a range of causes.

OBJECTIVE To determine short- and intermediate-term hearing preservation rates after microsurgical resection of vestibular schwannoma (VS). DATA SOURCES Systematic review of the Ovid, Cochrane, EMBASE, and Web of Science databases. STUDY SELECTION This study was restricted to full-text English-language articles detailing VS resection via the middle cranial fossa or retrosigmoid approaches. Documentation of pre- and posttreatment hearing outcomes with American Academy of Otolaryngology-Head and Neck Surgery, Gardner-Robertson, or word recognition score scales, as well as time to follow-up were required. Duplicate data sets, studies with >10% of patients with neurofibromatosis two, previous or nonsurgical VS treatment, case reports with

The cementless, tapered wedge, short femoral stem implant is commonly used in direct anterior approach (DAA) total hip arthroplasty (THA). The lack of access and visualization, however, may increase the risk of perioperative fracture and early failure. Therefore, the current study examined perioperative complications and 2-year implant survivorship following DAA THA performed using a fracture table and short, tapered wedge femoral stem. A retrospective analysis was conducted on patients having undergone DAA THA with a cementless, tapered wedge, short femoral stem. Perioperative fractures were noted and survivorship was determined by the incidence of revision surgery within a minimum 2-year follow-up period. A total 366 consecutive patients (441 hips) were identified in the cohort. Four patients (6 hips; 1.4%) were lost to follow-up and three patients died from unrelated causes. Average follow-up time for the remaining 359 patients (435 hips) was 32.9 ± 10.2 months. There were no intraoperative factures but three perioperative fractures within two weeks. Aseptic loosening occurred in one stem at 13 months, resulting in a 99.1% survival rate with a mean survival time of 23.8 ± 0.1 months (95% confidence interval: 23.6–24.0 months). The use of a short, tapered wedge femoral stem and a fracture table for DAA THA resulted in 0.7% periprosthetic fractures and only one aseptic loosening within 2 years. These results suggest that proper femoral exposure with the use of a fracture table and a short, tapered wedge femoral stem does not appear to increase the risk of periprosthetic femoral fracture.

OBJECTIVE To investigate the effect of phase polarity and charge balance of spinal cord stimulation (SCS) waveforms on pain behavior and gene expression in a neuropathic pain rodent model. We hypothesized that differing waveforms will result in diverse behavioral and transcriptomics expression due to unique mechanisms of action. MATERIALS AND METHODS Rats were implanted with a four-contact cylindrical mini-lead and randomly assigned to two control (no-pain and pain model) and five test groups featuring monophasic, as well as charge-unbalanced and charge-balanced biphasic SCS waveforms. Mechanical and cold allodynia were assessed to measure efficacy. The ipsilateral dorsal quadrant of spinal cord adjacent to the lead was harvested post-stimulation and processed to determine gene expression via real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Gene expression, SCS intensity (mA), and behavioral score as percent of baseline (BSPB) were statistically analyzed and used to generate correlograms using R-Studio. Statistical analysis was performed using SPSS22.0, and p

Aim: To study the diagnostic accuracy of surgeon performed ultrasound (SPU) in the diagnosis of children presenting with clinical suspicion of intussusception to a tertiary paediatric facility in NSW, Australia. Methods: Children under the age of 16 presenting to the emergency department with clinical features suggestive of intussusception were recruited. After obtaining consent SPU was performed by a Paediatric surgeon. All patients subsequently had an ultrasound performed in radiology department (RPU) on which management was based. Diagnosis and images of SPU were reviewed by an independent radiologist blinded to results of the formal study. Results: Of 7 children enrolled 5 were male. Age ranged from 3 months to 7 years (mean 2.64, SD 2.282), weight from 5.2kgs to 25.2kgs (mean 13.69, SD 6.721). Five out of the 7 children presented during day hours i.e. 8a.m.-5 p.m. (mean 12.72, SD 4.049). Mean time to SPU was 6.3 hours (SD7.1) and RPU was 8.3 hours (SD 7.6). SPU was earlier by 2 hours and correlation between SPU and RPU was 100 percent. Conclusion: SPU for intussusception can be performed early and accurately. Surgeons should train and use ultrasound as a reliable tool in evaluating the child with suspected intussusception.

Background The effectiveness of erythropoiesis-stimulating agents, which are the main stay of managing anaemia of chronic kidney disease (CKD), is largely dependent on adequate body iron stores. The iron stores are determined by the levels of serum ferritin concentration and transferrin saturation. These two surrogate markers of iron stores are used to guide iron replacement therapy. Most Aboriginal and/or Torres Islander Australians of the Northern Territory (herein respectfully referred to as First Nations Australians) with end-stage kidney disease have ferritin levels higher than current guideline recommendations for iron therapy. There is no clear evidence to guide safe and effective treatment with iron in these patients. We aim to assess the impact of intravenous iron treatment on all-cause death and hospitalisation with a principal diagnosis of all-cause infection in First Nations patients on haemodialysis with anaemia, high ferritin levels and low transferrin saturation Methods In a prospective open-label blinded endpoint randomised controlled trial, a total of 576 participants on maintenance haemodialysis with high ferritin (> 700 μg/L and ≤ 2000 μg/L) and low transferrin saturation ( Discussion The INFERR clinical trial will address significant uncertainty on the safety and efficacy of iron therapy in First Nations Australians with CKD with hyperferritinaemia and evidence of iron deficiency. This will hopefully lead to the development of evidence-based guidelines. It will also provide the opportunity to explore the causes of hyperferritinaemia in First Nations Australians from the Northern Territory. Trial registration This trial is registered with The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12620000705987. Registered 29 June 2020.

SummaryVaccinations against SARS-CoV-2 are effective in COVID-19. However, with limited vaccine access, vaccine hesitancy and variant breakthroughs, there is still a need for effective and safe early treatments. Two community-based clinical trials of the inhaled corticosteroid, budesonide, have recently been published showing and improvement in patients with COVID-19 treated early with budesonide1,2. To understand mechanistically how budesonide was beneficial, inflammatory mediators were assessed in the nasal mucosa of patients recruited to the Steroids in COVID (STOIC1) trial and a cohort of SARS-CoV-2 negative individuals. Here we show that in early COVID-19, elevation in viral response proteins and Th1 and Th2 inflammation occurs. Longitudinal sampling in the natural course of COVID-19 showed persistently high interferon levels and elevated concentrations of the eosinophil chemokine, CCL11. In patients who deteriorate, the initial nasal mucosal signal is characterised by a marked suppression of the early inflammatory response, with reduced concentrations of interferon and inflammatory cytokines, but elevated eosinophil chemokines. Systemic inflammation remained altered in COVID-19 patients, implying that even after symptom resolution, changes in immunological mediators do not resolve. Budesonide treatment decreased IL-33 and IFN-γ, implying a reduction in epithelial damage and dampening of the interferon response. Budesonide treatment also increased CCL17 concentrations, suggesting an improved T-cell response; and significantly alters inflammatory pathways giving further insight into how this treatment can accelerate patient recovery.Abstract Figure

Background The high burden of chronic kidney disease in First Nations peoples requires urgent attention. Empowering people to self-manage their own condition is key, along with promotion of traditional knowledge and empowerment of First Nations communities. This study explores the potential of a culturally responsive tool, already found to have high acceptability and feasibility among First Nations people, to support self-management for First Nations people with kidney failure. The Stay Strong app is a holistic wellbeing intervention. This study explores the suitability of the Stay Strong app to support self-management as shown by the readiness of participants to engage in goal setting. Data were collected during a clinical trial which followed adaption of research tools and procedures through collaboration between content and language experts, and community members with lived experience of kidney failure. Methods First Nations (i.e., Aboriginal and Torres Strait Islander) participants receiving haemodialysis in the Northern Territory (n = 156) entered a three-arm, waitlist, single-blind randomised controlled trial which provided collaborative goal setting using the Stay Strong app at baseline or at 3 months. Qualitative data gathered during delivery of the intervention were examined using both content and thematic analysis. Results Almost all participants (147, 94%) received a Stay Strong session: of these, 135 (92%) attended at least two sessions, and 83 (56%) set more than one wellbeing goal. Using a deductive approach to manifest content, 13 categories of goals were identified. The three most common were to: ‘connect with family or other people’, ‘go bush/be outdoors’ and ‘go home/be on country’. Analysis of latent content identified three themes throughout the goals: ‘social and emotional wellbeing’, ‘physical health’ and ‘cultural connection’. Conclusion This study provides evidence of the suitability of the Stay Strong app for use as a chronic condition self-management tool. Participants set goals that addressed physical as well as social and emotional wellbeing needs, prioritising family, country, and cultural identity. The intervention aligns directly with self-management approaches that are holistic and prioritise individual empowerment. Implementation of self-management strategies into routine care remains a key challenge and further research is needed to establish drivers of success.

ObjectivesThe steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.DesignCross-sectional study.Setting and participantsPlasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples.Outcome measuresReceipt of invasive mechanical ventilation (IMV) and in-hospital mortality.ResultsVitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (ConclusionsVitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism. These findings support early supplementation trials to determine if insufficiency is causal in progression to severe disease, and investigation of longer-term bone health outcomes.

Introduction/Background* The role of angiogenesis in ovarian cancer progression is well established. Bevacizumab has been demonstrated to have a survival advantage for a subgroup of women with stage 4 disease and those who have suboptimal debulking surgery. The search for a biomarker of Bevacizumab efficacy is elusive. Skin capillary density (SCD) is a dynamic marker that may provide a surrogate indicator of angiogenic activity and alter in response to treatment in cancer patients. Methodology A cohort of 50 women with stage 3 and 4 high grade serous cancer were enrolled over 2 years at University Hospitals Bristol, UK. Written informed consent was obtained from each participant. SCD was measured at baseline and at specified time points during treatment. Serum angiogenic markers (VEGF and Ang 1) and tissue micro vessel density and proliferation (ki67) were also measured and correlated with SCD. Longitudinal and survival analysis was conducted to ascertain changes in SCD during treatment and association with cancer outcomes including surgical resection, overall survival (OS) and progression free survival (PFS). Correlations were investigated between SCD and tumour vascularity. Result(s)* Capillary rarefaction occurred in all patients during cytotoxic treatment (p= Conclusion* Skin capillary rarefaction occurs during both cytotoxic and anti angiogenic treatment in women with ovarian cancer. SCD could be useful as a biomarker of response to treatment and cancer outcomes and act as a surrogate marker of angiogenesis in cancer. It is a reproducible, cheap and non-invasive investigation that is acceptable to patients and shows promise in helping to guide treatment and prognostic information in the era of personalised medicine.

Being able to estimate kidney decline accurately is particularly important in Indigenous Australians, a population at increased risk of developing chronic kidney disease and end stage kidney disease. The aim of this analysis was to explore the trend of decline in estimated glomerular filtration rate (eGFR) over a four year period using multiple local creatinine measures, compared with estimates derived using centrally-measured enzymatic creatinine and with estimates derived using only two local measures. Method: The eGFR study comprised a cohort of over 600 Aboriginal Australian participants recruited from over twenty sites in urban, regional and remote Australia across five strata of health, diabetes and kidney function. Trajectories of eGFR were explored on 385 participants with at least three local creatinine records using graphical methods that compared the linear trends fitted using linear mixed models with non-linear trends fitted using fractional polynomial equations. Temporal changes of local creatinine were also characterized using group-based modelling. Analyses were stratified by eGFR ( < 60; 60-89; 90-119 and ≥120ml/min/1.73m 2 ) and albuminuria categories ( < 3mg/mmol; 3-30mg/mmol; > 30mg/mmol). Results: Mean age of the participants was 48years, 64% were female and the median follow-up was 3years. Decline of eGFR was accurately estimated using simple linear regression models and locally measured creatinine was as good as centrally measured creatinine at predicting kidney decline in people with an eGFR < 60 and an eGFR 60-90ml/min/1.73m 2 with albuminuria. Analyses showed that one baseline and one follow-up locally measured creatinine may be sufficient to estimate short term (up to four years) kidney function decline. The greatest yearly decline was estimated in those with eGFR 60-90 and macro-albuminuria: -6.21 (-8.20, -4.23) ml/min/1.73m 2 . Conclusion: Short term estimates of kidney function decline can be reliably derived using an easy to implement and simple to interpret linear mixed effect model. Locally measured creatinine did not differ to centrally measured creatinine, thus is an accurate cost-efficient and timely means to monitoring kidney function progression. Refereed/Peer-reviewed

Over the last decade there has been a trend toward observation for small nongrowing vestibular schwannoma (VS). Even without tumor growth, patients commonly experience ipsilateral hearing decline, and hearing rehabilitation remains challenging. This study analyzes hearing and speech performance outcomes after cochlear implantation (CI) in observed VS.Retrospective review.Tertiary referral center.Chart review was used to include patients with observed VS who had undergone ipsilateral CI, pre- and postimplantation audiometry, and speech performance. Tumor size pre- and postimplantation was measured with volumetric analysis.Seven patients with ipsilateral VS and CI were identified. Preimplantation tumor volume was 0.11 to 1.02 cmOur results demonstrate that CI is a successful option for subjects with small nongrowing VS. All subjects had improved performance postimplantation. VS may continue to be observed with serial magnetic resonance imaging given increasing conditionality among CI manufacturers and ability to assess cerebellopontine angle extension despite implant artifact.

OBJECTIVE To examine the association between soluble tumor necrosis factor receptor 1 (sTNFR1) levels and kidney disease progression in Indigenous Australians at high risk of kidney disease. RESEARCH DESIGN AND METHODS This longitudinal observational study examined participants aged ≥18 years recruited from >20 sites across diabetes and/or kidney function strata. Baseline measures included sTNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR), HbA1c, C-reactive protein (CRP), waist-to-hip ratio, systolic blood pressure, and medical history. Linear regression was used to estimate annual change in estimated glomerular filtration rate (eGFR) for increasing sTNFR1, and Cox proportional hazards were used to estimate the hazard ratio (HR) and 95% CI for developing a combined renal outcome (first of a ≥30% decline in eGFR with a follow-up eGFR RESULTS Over a median of 3 years, participants with diabetes (n = 194) in the highest compared with the lowest quartile of sTNFR1 experienced significantly greater eGFR decline (−4.22 mL/min/1.73 m2/year [95% CI −7.06 to −1.38]; P = 0.004), independent of baseline age, sex, eGFR, and uACR. The adjusted HR (95% CI) for participants with diabetes per doubling of sTNFR1 for the combined renal outcome (n = 32) was 3.8 (1.1–12.8; P = 0.03). No association between sTNFR1 and either renal outcome was observed for those without diabetes (n = 259). CONCLUSIONS sTNFR1 is associated with greater kidney disease progression independent of albuminuria and eGFR in Indigenous Australians with diabetes. Further research is required to assess whether TNFR1 operates independently of other metabolic factors associated with kidney disease progression.

American journal of nephrology 52(10/11), 827-836 (2021). doi:10.1159/000519812, Published by Karger, Basel [u.a.]

Single-stage bilateral total knee arthroplasty (ssBTKA) can be used for patients presenting with bilateral arthritis and may result in fewer systemic and wound complications compared with two, independent procedures. However, the safety of ssBTKA in the elderly remains controversial. Therefore, the purpose of this study was to compare early complications and transfusion rates following ssBTKA in patients ≤ 70 years old or > 70 years old. This retrospective chart review of 313 consecutive patients undergoing ssBTKA included 174 patients ≤ 70 years old and 139 patients > 70 years old. Perioperative variables and postoperative complications were compared with univariate analyses between age groups. Multivariate analyses were performed to determine risk factors for developing perioperative complications and transfusions. Compared with patients ≤ 70, patients > 70 had significantly lower body mass index (p 0.12) and systemic complications (p > 0.54) were similar, 23% of patients > 70 required transfusion compared with only 8% of patients ≤ 70 (p 70 (p = 0.002), or diabetes mellitus (p = 0.007) were at 5.7, 3.3, and 2.9 times greater risk for requiring a transfusion, respectively. Patients > 70 undergoing ssBTKA have a similar complication profile to patients ≤ 70 years old, suggesting age should not be an absolute exclusion criterion for ssBTKA. However, the risk of transfusion was significantly higher in those > 70, despite lower tourniquet times. Treatment of preoperative anemia may decrease the risk of transfusion and could provide adequate safety for patients > 70 to undergo ssBTKA by an experienced surgeon.

BackgroundCOVID-19 is a multi-system disease and patients who survive may experience in-hospital complications. These complications are likely to have important short and long-term consequences for patients, healthcare utilisation, healthcare system preparedness, and society amidst the ongoing COVID-19 pandemic. Our aim was to characterise the extent and impact of COVID-19 complications, particularly in those who survive using the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK).MethodsA multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 17th January and 4th August 2020. Complications were defined as organ specific diagnoses occurring alone or in addition to any hallmarks of COVID-19 illness. Outcomes included death, critical care use, and ability to self-care at hospital discharge. We used multilevel logistic regression and survival models to explore associations between these outcomes and in-hospital complications, age, and pre-existing comorbidities.ResultsOf patients admitted to hospital for management of COVID-19, 49.7% (36 367/73 197) experienced at least one complication. The mean age of our cohort was 71.1 years old (SD 18.7), included more males (56.0%, 41 025/73 ) with 81.0% (59 289/73 197) of patients having at least one comorbidity. Males over 60 were most likely to experience a complication (60 y and over, 54.5% [16 579/30 416] in males and 48.2% [11 707/24 288] in females; Under 60 y, 48.8% [5179/10 609] in males, 36.6% [2814/7689] in females). Renal (24.3%, 17 752/73 197), complex respiratory 18.4% (13 486/73 197), and systemic (16.3%, 11 895/73 197) complications were most frequent. Cardiovascular (12.3%, 8973/73 197), neurological (4.3%, 3115/73 197), and gastrointestinal/liver (0.8%, 7901/73 197) complications were also reported. The presence of any complication was associated with significantly worse survival (adjusted HR 1.74, 95% CI 1.64 to 1.84) and increased admission to critical care (adjusted OR 7.25, 95% CI 6.83 to 7.69). Reduced ability to self-care at discharge was significantly greater in patients who experienced a complication (adjusted OR 2.42, 95% CI 2.31 to 2.54) and was greatest in those who experienced neurological complications (adjusted OR 4.39, 95% CI 3.95 to 4.89). ConclusionsComplications and worse functional outcomes in patients admitted to hospital with COVID-19 are high, even in young, previously healthy individuals. Acute complications are associated with reduced ability to self-care at discharge, with neurological complications being associated with the worst functional outcomes. COVID-19 complications are likely to cause significant strain on health and social care in the coming years. These data will help in the design and provision of services aimed at the post-hospitalisation care of patients with COVID-19.

Objectives BRCA 1 or 2 mutation carriers have increased risk of developing breast cancer (BC) and serous epithelial ovarian cancer (EOC). The incidence of BC over time after EOC is unknown. Optimal BC surveillance for BRCA mutation carriers following EOC has not been defined. Methods A multi-institutional retrospective chart review was performed. Patients with BRCA -associated EOC diagnosed between 1996 and 2016 were followed for an average of 80 months. Women with previous bilateral mastectomy were excluded; women with prior BC and an intact breast were included. Descriptive statistics, Chi Square, and univariate survival analysis were performed. Results 184 patients with BRCA -associated EOC were identified. Eighteen (10%) were diagnosed with BC a median of 48 months following EOC. Two (1%) with prior BC developed contralateral BC and 16 (9%) developed primary BC. The majority of BC (55%) was diagnosed 3 years following EOC. The 3-, 5- and 10-year incidence of BC was 5.6%, 9.5% and 33.3%. Annual mammography was performed in 43% and MRI in 34%. Twenty-eight (15%) women underwent risk-reducing mastectomy (RRM). There was no statistically significant difference in BC screening between women with, and without, a prior BC. BC was most commonly detected on mammogram. Three (17%) women had occult BC at the time of RRM. Nine (50%) had DCIS, and 8 (44%) had stage I/II BC. Median 5- and 10-year survival was 68% and 43% and was comparable between groups. Conclusions Ten percent of women developed BC after EOC. The incidence of BC following EOC in BRCA carriers increases over time, and surveillance is recommended given their enhanced survival of EOC. Timely genetic testing for women with EOC is imperative to better triage BC screening resources and treatment.

Endometriosis is associated with increased risk of epithelial ovarian cancers (EOCs). Data from large endometriosis and EOC genome-wide association meta-analyses were used to estimate the genetic correlation and evaluate the causal relationship between genetic liability to endometriosis and major EOC histotypes, and to identify shared susceptibility loci. We estimated a significant genetic correlation (rg) between endometriosis and clear cell (rg=0.71), endometrioid (rg=0.48) and high-grade serous (rg=0.19) ovarian cancer, all supported by Mendelian randomization analyses. A bivariate meta-analysis identified 28 loci associated with endometriosis and EOC, including two novel risk loci, and 19 with evidence for a single underlying causal variant. Differences in the shared risk suggest different underlying pathways may contribute to the relationship between endometriosis and the different histotypes. Functional annotation using transcriptomic and epigenomic profiles of relevant tissues/cells highlighted several target genes. This comprehensive analysis reveals profound genetic overlap between endometriosis and EOC histotypes with valuable genomic targets for understanding the biological mechanisms linking the diseases.