Proximal Junctional Degeneration and Failure Modes: A Novel Classification and Clinical Implications.

STUDY DESIGN: Case-control study. OBJECTIVE: To introduce a classification system that will include the major types of degenerative changes and failures related to the proximal junction, and to determine the clinical course and characteristics for the different types of proximal junctional degeneration (PJD). SUMMARY OF BACKGROUND DATA: Proximal junctional kyphosis (PJK) and failures are well recognized after adult spinal fusion, however, a standardized classification is lacking. METHODS: The proposed system identified four different patterns of PJD: Type 1 (multi-level symmetrical collapse), Type 2 (Single adjacent level collapse), Type 3 (fracture) and Type 4 (spondylolisthesis). A single center database was reviewed from 2018 to 2021. Patients ≥18 years of age, who underwent posterior spinal fusion of ≥3 levels with an upper instrumented vertebral level between T8-L2, and a follow-up of ≥2 years were included. Radiographic measurements, revision surgery and time to revision were the primary outcomes. RESULTS: 150 patients were included with a mean age of 65.1 (±9.8) years and a mean follow-up of 3.2 (±1) years. 69 patients (46%) developed significant degenerative changes in the proximal junction, and were classified accordingly. 20 (13%) were Type 1, 17 (11%) were Type 2, 22 (15%) were Type 3 and 10 (7%) were Type 4. Type 3 had a significantly shorter time to revision with a mean of 0.9 (±0.9) years. Types 3 and 4 had greater preoperative sagittal vertical axis, and Types 1 and 3 had greater final follow-up lumbar lordosis. Bone density measured by Hounsfield units showed lower measurements for Type 3. Types 1 and 4 had lower rates of developing PJK. Type 1 had the lowest revision rate with 40% (types 2, 3 and 4 were 77%, 73% and 80%, respectively, P=0.045). CONCLUSION: This novel classification system defines different modes of degeneration and failures at the proximal junction, and future studies with larger sample sizes are needed for validation. LEVEL OF EVIDENCE: 3.

Comparison of No Tap (two-step) and tapping robotic assisted cortical bone trajectory screw insertion.

Workflow for cortical bone trajectory (CBT) screws includes tapping line-to-line or under tapping by 1 mm. We describe a non-tapping, two-step workflow for CBT screw placement, and compare the safety profile and time savings to the Tap (three-step) workflow. Patients undergoing robotic assisted 1-3 level posterior fusion with CBT screws for degenerative conditions were identified and separated into either a No-Tap or Tap workflow. Number of total screws, screw-related complications, estimated blood loss, operative time, robotic time, and return to the operating room were collected and analyzed. There were 91 cases (458 screws) in the No-Tap and 88 cases (466 screws) in the Tap groups, with no difference in demographics, revision status, ASA grade, approach, number of levels fused or diagnosis between cohorts. Total robotic time was lower in the No-Tap (26.7 min) versus the Tap group (30.3 min, p = 0.053). There was no difference in the number of malpositioned screws identified intraoperatively (10 vs 6, p = 0.427), screws converted to freehand (3 vs 3, p = 0.699), or screws abandoned (3 vs 2, p = 1.000). No pedicle/pars fracture or fixation failure was seen in the No-Tap cohort and one in the Tap cohort (p = 1.00). No patients in either cohort were returned to OR for malpositioned screws. This study showed that the No-Tap screw insertion workflow for robot-assisted CBT reduces robotic time without increasing complications.

Predictors of segmental lumbar lordosis following midline posterior (transforaminal) lumbar interbody fusion: Does interbody device type matter?

Background: Controversy exists regarding the ability of posterior (transforaminal) lumbar interbody fusion (PLIF/TLIF) to achieve lordosis. We hypothesized that an interbody device (IBD) designed for positioning in the anterior disc space produces greater lordosis than IBDs designed for straight-in positioning. The purpose of this study is to determine if using either an anterior-position or straight-in position IBD design were associated with successful achievement of postoperative lordosis. Methods: A consecutive series of patients undergoing a undergoing a single-level, posterior open midline (transforaminal) lumbar interbody fusion procedure for degenerative spine conditions during a time period when the two types of interbody devices were being used at surgeon discretion were identified from a multi-surgeon academic training center. Patient demographics and radiographic measures including surgical level lordosis (SLL), anterior disc height, middle disc height, posterior disc height, IBD height, and IBD insertion depth were measured on preop, immediate postop, and one-year postop standing radiographs using PACS. Group comparison and regression analysis were performed using SPSS. Results: Sixty-one patients were included (n=37 anterior, n=34 straight-in). Mean age was 59.8±8.7 years, 32 (52%) were female. There was no difference between IBD type (anterior vs. straight-in) for mean Pre-op SLL (19±7° vs. 20±6°, p=0.7), Post-op SLL (21±5° vs 21±6°, p=0.5), or Change in SLL (2±4° vs. 1±5°, p=0.2). Regression analysis showed that Pre-op SLL was the only variable associated with Change in SLL (Beta = negative 0.48, p=0.000). While the mean Change in SLL could be considered clinically insignificant, there was wide variability: from a loss of 9° to a gain of 13°. Gain of lordosis >5° only occurred when Pre-op SLL was <21°, and loss of lordosis >5° only occurred when Pre-op SLL was >21°. Conclusions: While group averages showed an insignificant change in segmental lordosis following a posterior (transforaminal) interbody fusion regardless of interbody device type, pre-operative lordosis was correlated with a clinically significant change in segmental lordosis. Preoperative hypolordotic discs were more likely to gain significant lordosis, while preoperative hyperlordotic discs were more likely to lose significant lordosis. Surgeon awareness of this tendency can help guide surgical planning and technique.

Patient Perceptions Regarding Routine Oncologic Follow-Up for Urologic Malignancies.

INTRODUCTION: In colorectal, cervical, and breast cancers, oncologic follow-up can exacerbate or alleviate patient stress about disease recurrence. Such patient experiences are less well defined for urologic malignancies. We developed a cross-sectional prospective survey study to assess kidney (Kid), prostate (Pros), and bladder (Bld) cancer patient perceptions of oncologic follow-up following surgical treatment. PATIENTS AND METHODS: Patients with pTanyNanyM0 Kid, Pros, and Bld cancer presenting at least 60 days following primary surgical treatment of their cancer were eligible. Receipt of adjuvant therapy or disease recurrence were exclusion criteria. Questionnaires assessing attitudes towards follow-up and stress-reducing strategies were administered prior to revealing testing results. Analysis was performed according to cancer type and level of recurrence risk, with pathologic stage used a proxy for recurrence risk. RESULTS: Three hundred thirty-seven patients were prospectively surveyed from 2018 to 2020: 127 (38%) Kid, 134 (40%) Pros, and 76 (23%) Bld. Patients showed satisfaction with provided strategies to combat recurrence anxiety (Kid 86%, Pros 81%, Bld 85%). However, approximately 16% of patients reported wanting, but not receiving, strategies for fear reduction. Most patients reported diagnostic tests were "Not at All" burdensome (Kid 86%, Pros 94%, Bld 82%) and disagree that fewer tests would alleviate anxiety (Kid 89%, Pros 91%, Bld 84%). The majority reported an increased sense of worry if there were no cancer follow-ups (Kid 84%, Pros 80%, Kid 81%), and preferred their specialist to their family physician to direct such care (Kid 89%, Pros 91%, Bld 95%). When stratified by recurrence risk, no significant differences existed across cancers in patients' attitudes toward follow-up. However, Pros cancer patients showed a difference in fear of recurrence ("Not at All" worried about recurrence ≤T2 38%, ≥T3, 19%; P= .04). CONCLUSION: Urology patients appear satisfied with their oncologic follow-up. Sixteen percent of patients sought additional strategies to combat fear, indicating opportunity for improvement.

Biomembranes in bioelectronic sensing.

Cell membranes are integral to the functioning of the cell and are therefore key to drive fundamental understanding of biological processes for downstream applications. Here, we review the current state-of-the-art with respect to biomembrane systems and electronic substrates, with a view of how the field has evolved towards creating biomimetic conditions and improving detection sensitivity. Of particular interest are conducting polymers, a class of electroactive polymers, which have the potential to create the next step-change for bioelectronics devices. Lastly, we discuss the impact these types of devices could have for biomedical applications.

Drivers of in-hospital opioid consumption in patients undergoing lumbar fusion surgery.

BACKGROUND: With the current opioid crisis, as many as 38% of patients are still on opioids one year after elective spine surgery. Identifying drivers of in-hospital opioid consumption may decrease subsequent opioid dependence. We aimed to identify the drivers of in-hospital opioid consumption in patients undergoing 1-2-level instrumented lumbar fusions. METHODS: This is a retrospective cohort study. Electronic medical record analysts identified consecutive patients undergoing 1-2 level instrumented lumbar fusions for degenerative lumbar conditions from 2016 to 2018 from a single-center hospital administrative database. Oral, intravenous, and transdermal opioid dose administrations were converted to morphine milligram equivalents (MME). Linear regression analysis was used to determine associations between postoperative day (POD) 4 cumulative in-hospital MMEs and the patients' baseline characteristics including body mass index (BMI), race, American Society of Anesthesiologists (ASA) grade, smoking status, marital status, insurance type, zip code, number of fused levels, approach and preoperative opioid use. RESULTS: A total of 1,502 patients were included. The mean cumulative MMEs at POD 4 was 251.5. Linear regression analysis yielded four drivers including younger age, preoperative opioid use, current smokers and more levels fused. There were no associations with surgical approach, zip code, ASA grade, marital status, BMI, race or insurance type. CONCLUSIONS: Use of preoperative opioids and smoking are modifiable risk factors for higher in-hospital opioid consumption and can be targets for intervention prior to surgery in order to decrease in-hospital opioid use.

Is pelvic MRI imaging sufficient cross-sectional imaging for staging intermediate and high-risk prostate cancer?

OBJECTIVES: The American Urological Association's (AUA) and National Comprehensive Cancer Network's (NCCN) provide highly recognized guidelines for staging prostate cancer (CaP). However, both are vague as to specific type of cross-sectional imaging (CT vs. MRI) and extent (abdominal vs. pelvis), thereby raising concern for overlapping imaging. We investigated if current AUA and NCCN CaP staging guidelines can become more specific yet maintain sufficient staging. METHODS: We identified 493 patients diagnosed with CaP between 2011 and 2017 and focused analysis on those with AUA and NCCN Intermediate risk (IR) and High risk (HR) groups. Type of staging imaging was recorded and frequency of overlapping (CT + MRI) and abdominal imaging determined. Significance of radiologist findings, for both overlapping and abdominal imaging, were classified as nonurologic, nonsignificant urologic, and CaP significant. RESULTS: Among IR and HR AUA and NCCN risk groups, 82 (35.7%) and 95 (37.3%) patients, respectively, experienced overlapping imaging, of which only 7 patients in AUA and 9 patients in NCCN risk groups had an abnormal CT with normal MRI. However, only 3 of these CTs had CaP significant findings, of which 2 identified bone metastases, which were subsequently detected on bone scan. In regard to the extent of imaging, a total of 157 (68.2%) AUA and 178 (69.8%) NCCN IR and HR patients received abdominal scans, of which only 46 (20.0%) and 49 (19.2%) were abnormal among AUA and NCCN risk groups, respectively. Among these abnormal abdominal scans, only 10 showed CaP significant findings, of which half were suspected bone metastases, and confirmed on recommended bone scan. CONCLUSIONS: Due to nonspecific staging guidelines in IR and HR CaP regarding type and extent of cross-sectional imaging, patients are frequently receiving imaging of overlapping locations. Based on low occurrences of unique CaP significant findings on CT and abdominal imaging, our exploratory analysis suggests that narrowing cross-sectional imaging recommendations to pelvic MRI may reduce imaging overlap while maintaining sufficient staging.

Health-related quality-of-life improvement with lumbar fusion in patients with lower-extremity arthritis.

OBJECTIVE: Lumbar fusion can lead to significant improvements in patient-reported outcomes (PROs) in patients with degenerative conditions. It is unknown whether the presence of hip or knee arthritis confounds the responses of patients to low-back-specific PROs. This study examined PROs with lumbar fusion in patients with concomitant lower-extremity arthritis. The purpose of the current study was to examine whether patients with significant lower-extremity arthritis who undergo lumbar fusion achieve similar improvements in low-back-specific PROs compared to patients without lower-extremity arthritis. METHODS: Patients were identified from a prospectively enrolled multicenter registry of patients undergoing lumbar fusion surgery for degenerative conditions. Two hundred thirty patients identified with lumbar fusion and who also had concomitant lower-extremity arthritis were propensity matched to 233 patients who did not have lower-extremity arthritis based on age, BMI, sex, smoking status, American Society of Anesthesiologists grade, number of levels fused, and surgical approach. One-year improvement in PROs, numeric rating scales (0-10) for back and leg pain, and the Oswestry Disability Index and EuroQol-5D scores were compared for patients with and without lower-extremity arthritis. RESULTS: Baseline demographics and preoperative outcome measures did not differ between the two propensity-matched groups with 110 cases each. Patients with concomitant lower-extremity arthritis achieved similar improvement in health-related quality-of-life measures to patients without lower-extremity arthritis, with no significant differences between the groups (p > 0.10). CONCLUSIONS: The presence of lower-extremity arthritis does not adversely affect the results of lumbar fusion in properly selected patients. Patients with lower-extremity arthritis who undergo lumbar fusion can achieve meaningful improvement in PROs similar to patients without arthritis.

Drivers for nonhome discharge in a consecutive series of 1502 patients undergoing 1- or 2-level lumbar fusion.

OBJECTIVE: Unexpected nonhome discharge causes additional costs in the current reimbursement models, especially to the payor. Nonhome discharge is also related to longer length of hospital stay and therefore higher healthcare costs to society. With increasing demand for spine surgery, it is important to minimize costs by streamlining discharges and reducing length of hospital stay. Identifying factors associated with nonhome discharge can be useful for early intervention for discharge planning. The authors aimed to identify the drivers of nonhome discharge in patients undergoing 1- or 2-level instrumented lumbar fusion. METHODS: The electronic medical records from a single-center hospital administrative database were analyzed for consecutive patients who underwent 1- to 2-level instrumented lumbar fusion for degenerative lumbar conditions during the period from 2016 to 2018. Discharge disposition was determined as home or nonhome. A logistic regression analysis was used to determine associations between nonhome discharge and age, sex, body mass index (BMI), race, American Society of Anesthesiologists grade, smoking status, marital status, insurance type, residence in an underserved zip code, and operative factors. RESULTS: A total of 1502 patients were included. The majority (81%) were discharged home. Factors associated with a nonhome discharge were older age, higher BMI, living in an underserved zip code, not being married, being on government insurance, and having more levels fused. Patients discharged to a nonhome facility had longer lengths of hospital stay (5.6 vs 3.0 days, p < 0.001) and significantly increased hospital costs ($21,204 vs $17,518, p < 0.001). CONCLUSIONS: Increased age, greater BMI, residence in an underserved zip code, not being married, and government insurance are drivers for discharge to a nonhome facility after a 1- to 2-level instrumented lumbar fusion. Early identification and intervention for these patients, even before admission, may decrease the length of hospital stay and medical costs.

A Netnographic Approach: Views on Assisted Dying for Individuals With Dementia.

Alongside increasing rates of dementia diagnoses worldwide, efforts to seek alternative end-of-life options also increase. While the concept of assisted dying remains controversial, the discussion around its provision for people with dementia raises even more sensitivity. In this study, we explored how the practice of assisted dying for people with dementia is conceptualized and understood using the shared narratives of online contributors. An observational netnography over 20 months was carried out within five open Facebook communities. Thematic analysis was conducted on 1,007 online comments about assisted dying and dementia. Results reflected four central themes and five subthemes: understanding dementia; understanding assisted dying laws; caregivers' feelings; and moral/personal dilemmas. Findings reveal that the majority of communities' contributors fear developing dementia. They support the provision of advance euthanasia directives-written by competent patients-to prevent unnecessary suffering, and protect patients' wishes and freedom of choice when decision-making competency is lost.

Accuracy of WatchPAT for the Diagnosis of Obstructive Sleep Apnea in Patients with Chronic Obstructive Pulmonary Disease.

The co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), termed the overlap syndrome (OVS), is associated with adverse outcomes that may be reversed with treatment. However, diagnosis is limited by the apparent need for in-laboratory polysomnography (PSG). WatchPAT is a portable diagnostic device that is validated for the diagnosis of OSA that might represent an attractive tool for the diagnosis of OVS.Subjects with established COPD were recruited from a general population. Subjects underwent PSG and simultaneous recording with WatchPAT. Pulmonary function testing and questionnaires were also performed.A total of 36 subjects were recruited and valid data was obtained on 33 (age 63 ± 7, BMI 28 ± 7, 61% male, FEV1 56 ± 20% predicted). There was no significant difference in the apnea-hypopnea index (AHI) between PSG and WatchPAT (19 ± 20 versus 20 ± 15 events/h; mean difference 2(-2, 5) events/h; p = 0.381). The AHI was not significantly different in rapid eye movement (REM) and non-rapid eye movement (NREM) determined by PSG versus REM and NREM determined by WatchPAT. WatchPAT slightly overestimated total and REM sleep time, and sleep efficiency. The sensitivity of WatchPAT at an AHI cut-off of ≥5, ≥15, and ≥30 events/h for corresponding PSG AHI cut-offs was 95.8, 92.3, and 88.9, respectively; specificity was 55, 65.0, and 95.8, respectively.WatchPAT is able to determine OSA reliably in patients with COPD. The availability of this additional diagnostic modality may lead to improved detection of OVS, which may in turn lead to improved outcomes for a group of COPD patients at high risk of poor outcomes.

Index episode-of-care propensity-matched comparison of transforaminal lumbar interbody fusion (TLIF) techniques: open traditional TLIF versus midline lumbar interbody fusion (MIDLIF) versus robot-assisted MIDLIF.

OBJECTIVE: Posterior fixation with interbody cage placement can be accomplished via numerous techniques. In an attempt to expedite recovery by limiting muscle dissection, midline lumbar interbody fusion (MIDLIF) has been described. More recently, the authors have developed a robot-assisted MIDLIF (RA-MIDLIF) technique. The purpose of this study was to compare the index episode-of-care (iEOC) parameters between patients undergoing traditional open transforaminal lumbar interbody fusion (tTLIF), MIDLIF, and RA-MIDLIF. METHODS: A retrospective review of a prospective, multisurgeon surgical database was performed. Consecutive patients undergoing 1- or 2-level tTLIF, MIDLIF, or RA-MIDLIF for degenerative lumbar conditions were identified. Patients in each cohort were propensity matched based on age, sex, smoking status, BMI, diagnosis, American Society of Anesthesiologists (ASA) class, and number of levels fused. Index EOC parameters such as length of stay (LOS), estimated blood loss (EBL), operating room (OR) time, and actual, direct hospital costs for the index surgical visit were analyzed. RESULTS: Of 281 and 249 patients undergoing tTLIF and MIDLIF, respectively, 52 cases in each cohort were successfully propensity matched to the authors' first 55 RA-MIDLIF cases. Consistent with propensity matching, there was no significant difference in age, sex, BMI, diagnosis, ASA class, or levels fused. Spondylolisthesis was the most common indication for surgery in all cohorts. The mean total iEOC was similar across all cohorts. Patients undergoing RA-MIDLIF had a shorter average LOS (1.53 days) than those undergoing either MIDLIF (2.71 days) or tTLIF (3.58 days). Both MIDLIF and RA-MIDLIF were associated with lower EBL and less OR time compared with tTLIF. CONCLUSIONS: Despite concerns for additional cost and time while introducing navigation or robotic technology, a propensity-matched comparison of the authors' first 52 RA-MIDLIF surgeries with tTLIF and MIDLIF showed promising results for reducing OR time, EBL, and LOS without increasing cost.

Multi-modal pain control regimen for anterior lumbar fusion drastically reduces in-hospital opioid consumption.

BACKGROUND: The opioid epidemic is at epic proportions currently in the United States. Exposure to opioids for surgery and subsequent postoperative pain management is a known risk factor for opioid dependence. In addition, opioids can have a negative impact on multiple aspects including clinical outcomes, length of hospital stay, and overall cost of care. Thus, the greatest effort to reduce perioperative opioid use is necessary and a multimodal pain control (MMPC) has been gaining popularity. However, its efficacy in spine surgery is not well known. We aimed to evaluate the efficacy of a MMPC protocol in patients undergoing lumbar single-level anterior lumbar interbody fusion (ALIF). METHODS: This is a retrospective comparative study. From a prospective, single-surgeon, surgical database, consecutive patients undergoing single-level ALIF with or without subsequent posterior fusion for degenerative lumbar conditions were identified before and after initiation of the MMPC protocol. The MMPC protocol consisted of a preoperative oral regimen of cyclobenzaprine (10 mg), gabapentin (600 mg), acetaminophen (1 g), and methadone (10 mg). Postoperatively they received a bilateral transverse abdominis plane block with 0.5% Ropivacaine prior to extubation. We compared in-hospital opioid consumption between the MMPC and non-MMPC cohorts as well as baseline demographic, the length of hospital stay, cost, and rate of postoperative ileus. Opioid consumption was calculated and normalized to the morphine milligram equivalents (MMEs). RESULTS: In total, 68 patients in the MMPC cohort and 39 in the non-MMPC cohort were identified. There was no difference in baseline demographics including sex, body mass index, smoking status, or preoperative opioid use between the two groups. Although there was no difference in the MMEs on the day of surgery (58.5 vs. 66.9, P=0.387), cumulative MMEs each day after surgery was significantly lower in the MMPC cohort, with final cumulative MMEs being reduced by 62% (120.2 vs. 314.8, P<0.001). There was no difference in postoperative ileus, length of stay, and hospital costs. CONCLUSIONS: The use of a MMPC protocol in patients undergoing single-level ALIF for degenerative conditions reduced opioid consumption starting on the first day after surgery, resulting in a cumulative reduction of 62%.

Intensity-Modulated Radiotherapy With a Simultaneous Integrated Boost in Rectal Cancer.

AIMS: Dose-response curves suggest that higher doses of radiotherapy improve the complete response rate in rectal cancer. The UK adopted the EXPERT trial dose and fractionation, 45 Gy in 25 fractions to the pelvis with a sequential 9 Gy in five fractions to the gross tumour, in patients where the aim was to maximise the complete response. In the Oxford University Hospital NHS Foundation Trust (Oxford, UK) we deliver a biological equivalent dose (BED5) in selected patients using intensity-modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) in 25 fractions. We carried out a retrospective analysis of our series to: (i) document the toxicity of this protocol; (ii) ascertain whether dose constraints from RTOG 0822 were appropriate; (iii) assess the response. MATERIALS AND METHODS: The demographics and treatment details for all consecutive patients treated with this protocol were collected using electronic systems. Patients received 45 Gy to the elective nodes and 52 Gy using a SIB to the gross tumour with capecitabine chemotherapy using IMRT or RapidArc plans. Acute toxicity was collected prospectively during weekly reviews. For the purpose of this study, a dedicated gastrointestinal radiologist reviewed all baseline and post-treatment magnetic resonance images and assigned a magnetic resonance tumour regression grade (mrTRG). RESULTS: Seventy-one patients were identified. Seventy completed radiotherapy with a median overall treatment time of 34 days (range 32-36 days); 67.6% received full-dose chemotherapy, with 21.2% receiving a reduced dose. There was a 4.2% incidence of grade 3+ non-haematological toxicity and 1.5% grade 3 + haematological toxicity. 4.2% were admitted during their radiotherapy, with one death due to a pelvic abscess. The RTOG 0822 constraints were achieved in ≥75% of cases, other than the high-dose bladder constraint. mrTRG 1-2 was seen in 47.8%, with mrTRG 1 seen in 23.9%. CONCLUSIONS: We suggest that our protocol shows acceptable acute toxicity, with promising mrTRG results, and could be adopted by centres as an IMRT equivalent dose for EXPERT dose and fractionation.

World Trade Center exposure, post-traumatic stress disorder, and subjective cognitive concerns in a cohort of rescue/recovery workers.

OBJECTIVE: To determine whether World Trade Center (WTC)-exposure intensity and post-traumatic stress disorder (PTSD) are associated with subjective cognitive change in rescue/recovery workers. METHOD: The population included 7875 rescue/recovery workers who completed a subjective cognition measure, the Cognitive Function Instrument (CFI), between 3/1/2018 and 2/28/2019 during routine monitoring, indicating whether they had experienced cognitive and functional difficulties in the past year. Higher scores indicated greater self-perceived cognitive change. Probable PTSD, depression, and alcohol abuse were evaluated by validated mental health screeners. Logistic regression assessed the associations of WTC exposure and current PTSD with top-quartile (≥2) CFI score, and of early post-9/11 PTSD with top-quartile CFI in a subpopulation (N = 6440). Models included demographics, smoking, depression, and alcohol abuse as covariates. RESULTS: Mean age at CFI completion was 56.7 ± 7.7 (range: 36-81). Participants with high-intensity WTC exposure had an increased likelihood of top-quartile CFI score (odds ratio[OR] vs. low exposure: 1.32, 95%CI: 1.07-1.64), controlling for covariates. Current and early PTSD were both associated with top-quartile CFI (OR: 3.25, 95%CI: 2.53-4.19 and OR: 1.56, 95%CI: 1.26-1.93) respectively. CONCLUSIONS: High-intensity WTC exposure was associated with self-reported cognitive change 17 years later in rescue/recovery workers, as was PTSD. Highly WTC-exposed subgroups may benefit from additional cognitive evaluation and monitoring of cognition over time.

Outcome of Weekly Carboplatin-Paclitaxel-based Definitive Chemoradiation in Oesophageal Cancer in Patients Not Considered to be Suitable for Platinum-Fluoropyrimidine-based Treatment: A Multicentre, Retrospective Review.

AIMS: Although cisplatin-fluoropyrimidine-based definitive chemoradiotherapy (dCRT) is a standard of care for oesophageal cancer, toxicity is significant and limits its use in elderly and frail patients. Weekly carboplatin-paclitaxel-based dCRT provides a viable alternative, although prospective data are lacking in the dCRT setting. Here we report the results of a national, multicentre retrospective review of outcome in patients treated with weekly carboplatin-paclitaxel-based dCRT. MATERIALS AND METHODS: In this multicentre retrospective study of nine radiotherapy centres across the UK we evaluated the outcome of patients who had non-metastatic, histologically confirmed carcinoma of the oesophagus (adenocarcinoma, squamous cell or undifferentiated; World Health Organization performance status 0-2; stage I-III disease) and had been selected to receive weekly carboplatin-paclitaxel-based dCRT as they were considered not suitable for cisplatin-fluoropyrimidine-based dCRT. dCRT consisted of carboplatin AUC 2 and paclitaxel 50 mg/m2 (days 1, 8, 15, 22, 29) and the recommended radiation dose was 50 Gy in 25 daily fractions. We assessed overall survival, progression-free survival (PFS; overall, local and distant), proportion of patients who were failure free at the response assessment (12 weeks after dCRT), treatment compliance and toxicity. RESULTS: In total, 214 patients from nine UK centres were treated between 15 February 2013 and 19 March 2019: 39.7% of patients were ≥75 years; 18.7% ≥ 80 years. Indications for weekly carboplatin-paclitaxel-based dCRT were comorbidities (47.2%), clinician choice (36.4%) and poor tolerance/progression on cisplatin-fluoropyrimidine induction chemotherapy (15.8%). The median overall survival was 24.28 months (95% confidence interval 20.07-30.09) and the median PFS was 16.33 months (95% confidence interval 14.29-20.96). Following treatment, 69.1% (96/139) had a combined complete response on endoscopy with non-progression (complete response/partial response/stable disease) on imaging. The 1- and 2-year overall survival rates for this patient group were 81.9% (95% confidence interval 75.6-86.8%) and 50.6% (95% confidence interval 40.5-60.0%), respectively. Thirty-three per cent (n = 70) of patients experienced at least one grade 3 + acute toxicity (grade 3/4 haematological: 10%; grade 3/4 non-haematological: 32%) and there were no treatment-related deaths. 86.9% of patients completed at least four cycles of concomitant weekly carboplatin-paclitaxel-based chemotherapy and planned radiotherapy was completed in 97.7% (209/214). CONCLUSION: Weekly carboplatin-paclitaxel-based CRT seems to be well tolerated in elderly patients and in those with comorbidities, where cisplatin-fluoropyrimidine-based dCRT is contraindicated. Survival outcomes are comparable with cisplatin-fluoropyrimidine-based dCRT.

Schistosoma mansoni cathepsin D1: Biochemical and biophysical characterization of the recombinant enzyme expressed in HEK293T cells.

Schistosomes express a variety of aspartyl proteases (APs) with distinct roles in the helminth pathophysiology, among which degradation of host haemoglobin is key, since it is the main amino acid source for these parasites. A cathepsin D-like AP from Schistosoma mansoni (SmCD1) has been used as a model enzyme for vaccine and drug development studies in schistosomes and yet a reliable expression system for readily producing the recombinant enzyme in high yield has not been reported. To contribute to further advancing the knowledge about this valuable antischistosomal target, we developed a transient expression system in HEK 293T mammalian cells and performed a biochemical and biophysical characterization of the recombinant enzyme (rSmCD1). It was possible to express a recombinant C-terminal truncated form of SmCD1 (rSmCD1ΔCT) and purify it with high yield (16 mg/L) from the culture supernatant. When analysed by Size-Exclusion Chromatography and multi-angle laser light scattering, rSmCD1ΔCT behaved as a dimer at neutral pH, which is unusual for cathepsins D, turning into a monomer after acidification of the medium. Through analytical ultrancentrifugation, the dimer was confirmed for free rSmCD1ΔCT in solution as well as stabilization of the monomer during interaction with pepstatin. The mammalian cell expression system used here was able to produce rSmCD1ΔCT with high yields allowing for the first time the characterization of important kinetic parameters as well as initial description of its biophysical properties.

An Under-Recognised Cause of Iatrogenic, Severe Metabolic Acidosis

Case Pyroglutamic acidosis is an uncommonly diagnosed but important cause of a high anion gap metabolic acidosis. Our case report concerns an elderly male admitted to the Intensive Care Unit (ICU) following the acute onset of coma which developed during treatment of a prosthetic joint infection. A diagnosis of pyroglutamic acidosis was ultimately made and later confirmed with laboratory testing. Blood gas analysis revealed a profound high anion gap metabolic acidosis. Treatment Treatment included withdrawal of the precipitating medications, N-acetylcysteine and sodium bicarbonate. Discussion This case highlights an unusual cause of severe metabolic acidosis caused by commonly used medications and readily reversible if recognised. This is of particular relevance in elderly, frail patients as incorrect alternate diagnoses may result in decisions which incorrectly limit critical care therapies.

Psychiatric consultation in the nursing home: reasons for referral and recognition of delirium.

OBJECTIVE: To describe the behavioural and psychiatric problems found in nursing home psychiatric referrals in the Dublin South city area. METHODS: We undertook two consecutive surveys of nursing home referrals to the St James's Hospital psychiatry of old age service over a 2-year period. During the second survey a new clinical nurse specialist was specifically appointed to manage the seven nursing homes included in the study. RESULTS: The most common reason for referral during survey one was uncooperative/aggressive behaviour (22%). For survey two, patients were most commonly referred for low mood (31%) or agitation (29%). During survey one, the majority of patients assessed were diagnosed with behavioural and psychological symptoms of dementia (41%). This was also a prevalent diagnosis during survey two, affecting 27% of those referred. Only 7% of patients were considered to be delirious during survey one. This rose to 31% the following year making it the most common diagnosis during survey two. Over the 2-year study period, 7% of referred patients were diagnosed with depression. In terms of prescribing practices, the discontinuation rate of antipsychotic mediation following psychiatric input was 13% in survey one. By survey two, this had risen to 47%. CONCLUSIONS: Delirium is often undetected and untreated in nursing homes. Residents presenting with psychiatric symptoms should undergo routine bloods and urinalysis prior to psychiatric referral. Dedicated input from trained psychiatric nursing staff can lead to both an improvement in the recognition of delirium and reduced prescribing rates of antipsychotic medication.