Short-term Cohort Research Articles

Utility of a Neuromuscular Activation Exercise Protocol on Surgeon Posture.

Surgeons are at risk for musculoskeletal disorders from ergonomic strain in the operating room. These deficits may stem from neuromuscular control deficits. Neuromuscular activation exercises (NMEs) may strengthen the brain-muscle connection. This study aimed to assess the utility of a surgeon-oriented NME protocol on posture. Surgeons, operating room staff, and medical students completed a professionally established NME routine. An electronic application, PostureScreen®, assessed participants' posture. A long-term cohort was assessed before and after a 2 to 6-week routine. A short-term cohort was assessed immediately before and after completion. All participants additionally completed a postintervention survey. After intervention, the short-term cohort (n = 47) had significantly reduced frontal and sagittal postural deviation (P < 0.05). A significant decrease in effective head weight was additionally demonstrated with decreased neck flexion and increased cerebral-cervical symmetry (P < 0.05).The long-term cohort (n = 6) showed a significant postintervention decrease in lateral and anterior shoulder translation (P < 0.05). Total anterior translational deviations demonstrated trend-level decrease (P = 0.078). This demonstrates that after intervention, participants' shoulders were more centered with the spine as opposed to shifted right or left. Survey results showed participants favored exercises that immediately brought relief of tension. A decrease in postural deviations associated with NME in both cohorts demonstrates NME as a potential mechanism to protect surgeon musculoskeletal health and improve well-being. Survey results demonstrate areas of refinement for NME protocol design.

Longitudinal study of cognitive decline among women with and without urinary incontinence

BACKGROUNDCross-sectional and short-term cohort studies have demonstrated an association between urinary incontinence and dementia as well as lower performance on cognitive testing. The Health and Retirement Study, a longitudinal study of community-dwelling older adults, offers an opportunity to assess the temporal association between these conditions, as this study included an assessment of incontinence symptoms as well as biennial assessments of cognitive function. OBJECTIVESThis study aimed to evaluate if urinary incontinence before age 70 had an effect on changes in cognitive function among women participating in the Health and Retirement Study. STUDY DESIGNThis secondary analysis included data from female respondents in the Health and Retirement Study ages 58 to 67 years with ≥2 cognitive assessments. Urinary incontinence was defined as any involuntary loss of any urine in the preceding 12 months. A control group without incontinence was reweighted for better comparability using coarsened exact matching for age and comorbidities. Validated methods, including neuropsychological test data, estimated a Memory score and DP for each participant biennially. Coprimary outcomes were the changes in Memory score and dementia probability.Linear regression models were used to estimate the association of urinary incontinence with change in Memory score and dementia probability, adjusting for baseline demographics and comorbidities. A subgroup analysis was performed to assess the effects of urinary incontinence frequency on these outcomes. The infrequent subgroup reported less than fifteen days of leakage per month and the frequent subgroup reported fifteen or more days of leakage per month. RESULTSAmong eligible female respondents, 40.6% reported urinary incontinence between ages 58 to 69 years. Baseline Memory scores and dementia probability were similar between those with urinary incontinence (n=1706) and controls (n=2507). Memory score declined significantly in both cohorts, indicating poorer memory over time -0.222 among those with incontinence (95% confidence interval (CI) -0.245, -0.199) versus -0.207 in controls (95% CI: -0.227, -0.188). The decline of Memory score was not statistically different between cases and controls (mean difference -0.015, 95% CI: -0.045, 0.015). Dementia probability increased significantly in both groups, indicating a greater probability of dementia: 0.018 among those with incontinence (95% CI: 0.015, 0.020) and by 0.020 among controls (95% CI: 0.017, 0.022). The change in DEMENTIA PROBABILITY was not significantly different between groups (mean difference -0.002, 95% CI: -0.006, 0.002).Frequent urinary incontinence was reported in 105/1706 (6%) with urinary incontinence. Memory score declined and dementia probability increased with time (p<0.001) in frequent and infrequent UI subgroups. There was no dose-response relationship. CONCLUSIONSMeasures of cognitive performance declined with approximately 10 years of observation; the changes in performance were not associated with the presence of urinary incontinence in their younger years.

A109 A COMPARISON OF MULTIMORBIDITY AT DEATH AMONG PERSONS WITH AND WITHOUT INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED STUDY

Abstract Background With improved care and life-expectancy, people with IBD are living longer and more likely to develop multiple chronic conditions. However, research on co-morbidities in the IBD population has typically focused on co-occurrences of a specific disease alongside IBD and employed a cross-sectional or short-term cohort perspective. To date, no work has taken a life-course perspective, evaluating retrospectively from death, to identify the population-level burden of multimorbidity. Aims To identify the burden of chronic conditions at time of death among people with IBD relative to their non-IBD counterparts. Methods We conducted a retrospective matched cohort study using health administrative data from Ontario, Canada. Individuals with IBD (identified using a validated algorithm) who died between 2010 to 2020 were matched to controls (1:5 ratio) based on sex, age at death, and year of death. We calculated the proportion of decedents with each of 17 different chronic conditions and the number of conditions at death. Conditions were identified using validated algorithms or clusters of diagnostic codes (when validated algorithms were not available). The number of chronic conditions at death among people with and without IBD was modeled using Poisson regression adjusting for Ontario Marginalization Index and accounting for matching. Results At the time of death, people with IBD (n=9728) were more likely than matched controls (n=42,389) to have mood disorders (69.0% vs. 60.2%), asthma (21.4% vs. 16.5%), renal failure (49.6% vs. 38.5%), osteoarthritis (76.8 vs. 67.6%), and osteoporosis (21.2% vs. 12.8%) (Figure 1B). Compared to their controls, people with IBD had were more likely to have ≥5 conditions (77.8% vs. 70.1%) (Figure 1A). People with IBD had significantly more chronic health conditions (RR 1.11, 95% CI 1.10-1.12). Conclusions People with IBD accumulate a greater degree of morbidity compared to those without IBD. Our findings add a novel understanding of multimorbidity among those with IBD from a life-course perspective. Our research highlights the need to provide quality multi-disciplinary care to people with IBD across the life course to address the increased frequency of multimorbidity. Funding Agencies ACG

Temporal stability of fecal metabolomic profiles in irritable bowel syndrome.

The potential of the fecal metabolome to serve as a biomarker for irritable bowel syndrome (IBS) depends on its stability over time. Therefore, this study aimed to determine the temporal dynamics of the fecal metabolome, and the potential relationship with stool consistency, in patients with IBS and healthy subjects. Fecal samples were collected in two cohorts comprising patients with IBS and healthy subjects. For Cohort A, fecal samples collected during 5 consecutive days were analyzed by gas chromatography-tandem mass spectrometry (GC-MS/MS). For Cohort B, liquid chromatography-MS (LC-MS) was used to analyze fecal samples collected at week 0 (healthy and IBS) and at week 4 (patients only). Stool consistency was determined by the Bristol Stool Form scale. Fecal samples were collected from Cohort A (seven healthy subjects and eight IBS patients), and Cohort B (seven healthy subjects and 11 IBS patients). The fecal metabolome of IBS patients was stable short-term (Cohort A, 5 days and within the same day) and long-term (Cohort B, 4 weeks). A similar trend was observed over 5 days in the healthy subjects of Cohort A. The metabolome dissimilarity was larger between than within participants over time in both healthy subjects and IBS patients. Further analyses showed that patients had greater range of stool forms (types) than healthy subjects, with no apparent influence on metabolomic dynamics. The fecal metabolome is stable over time within IBS patients as well as healthy subjects. This supports the concept of a stable fecal metabolome in IBS despite fluctuations in stool consistency, and the use of single timepoint sampling to further explore how the fecal metabolome is related to IBS pathogenesis.

Effects of personal noise exposure, sleep quality, and burnout on quality of life: An online participation cohort study in Taiwan

Chronic noise exposure in daily life not only causes physical and mental illness but also reduces quality of life. However, collecting objective data on sound exposure and subjective acoustic comfort through a traditional one-shot survey is difficult. This study applied online chatbots in social media to explore the effects of daily sound exposure, personal characteristics, noise sensitivity, burnout status, and sleep quality on quality of life using a short-term participatory cohort design. During the two-month survey in 2022, 207 participants completed at least 15 days of collection of data on sound exposure and perception, as well as periodic structural questionnaires during the follow-ups. Linear regression and generalized linear models were applied to explore the factors influencing personal burnout, the Pittsburgh Sleep Quality Index, and quality of life. A chain mediation model was applied to explore the direct and indirect effects of noise exposure on quality of life. The results showed a better quality of life among respondents who rated their home environment better, were in good health, had better daily acoustic comfort, and were less exposed to noise during the week. In contrast, respondents with lower daily acoustic comfort and a higher frequency of noise-induced sleep disturbances and mood disorders were more likely to have poorer sleep quality. A higher personal burnout was associated with poorer health, longer exposure to noise during the week, a higher frequency of noise-induced illnesses, and neurotic traits. In the mediation analyses, noise-induced sleep disturbance and better daily acoustic comfort also had important direct influences on quality of life compared to the indirect pathway through sleep quality and personal burnout. In conclusion, noise exposure in daily life not only exacerbated poor sleep quality and personal burnout but also reduced quality of life.

Functional Outcome of Mechanical Alignment in Total Knee Arthroplasty Surgery: A Short-Term Cohort Study at an Indian Tertiary Care Hospital.

In severe arthritis cases, goal of total knee arthroplasty (TKA) management is to attain pain-free joint and restore the overall limb alignment. There are limitedshort-term studies publishedfrom Indian hospitals that investigated the importance of neutral mechanical component alignment in TKA patients. Retrospective and prospective study was conducted at the Department of orthopaedics, Sancheti Institute for Orthopaedics and Rehabilitation, Pune from June 2020 to September 2022. Enrolled patients were assessed preoperatively and postoperatively using clinical examination, radiological assessment and functional outcomes through the Oxford knee score, Knee society score and VAS score. 204 patients enrolled, and 267 knees were evaluated for the study. Osteoarthritis was the commonest diagnosis (254 knees, 95.13%). Pre-operatively, 92.13% knees were varus, 4.87% valgus and 3% neutral while post-operatively, 51.69% were varus, 16.1% were valgus, and 32.32% were with neutral axis. Majority of patients with a pre-operative neutral axis converted to varus axis (62.5%), while most valgus axis cases preoperatively converted to a neutral axis (53.84%). For pre-operative varus subgroup, the majority patients with < 10° pre-operative axis converted to neutral (41.28%). Majority patients with 10°-20° pre-operative axis remained varus (60.53%) and with > 20° pre-operative axis remained varus (78.26%). Functional outcome parameters were significantly improved at follow-up (P < 0.05). Short-term postoperative functional scores were significantly improved in postoperative cases, with the postoperative alignment of 0° ± 3° relative to the mechanical axis was achieved. Thus, postoperative neutral mechanical alignment of 0° ± 3° can be the standard of care for patients undergoing TKA.

Evaluation of longer- vs short-term use of patiromer on health care resource utilization in the patiromer longer-term use evaluation (VALUE) study.

Studies suggest that continuous long-term use of patiromer by patients with hyperkalemia is associated with less health care resource utilization compared with not using potassium binders. To retrospectively evaluate health care resource utilization and costs with longer-term adherent vs short-term use of patiromer. Time-restricted extracts from Optum's de-identified Clinformatics® Data Mart Database (CDM; January 2016-May 2019) and Symphony Health (SHA; January 2016-September 2018) deidentified databases were analyzed. Both include participants enrolled in commercial and privatized public insurance programs (SHA includes some government programs). Both integrate health care claims data from medical and pharmacy claims. Patients aged 18 years or older with hyperkalemia and an index patiromer prescription were selected. Patiromer use was identified as short-term (<2 months) and any fill quantity or adherent longer-term with claims for at least 2 consecutive months and fill quantities of at least 80% of the total days. Groups were matched on multiple categorical covariates to control for demographic variables, baseline characteristics, and markers of disease severity. Random sampling without replacement was performed 50 times to identify 50 sets of patients matched from the short-term cohort to the longer-term cohort. Health care costs/charges and encounters were compared for a 6-month post-index period using t-tests. Of the CDM patients, 1,267 (40.2%) vs 1,887 (59.8%) and of the SHA patients, 2,234 (35.1%) vs 4,132 (64.9%) experienced longer-term vs short-term patiromer use, respectively. Patient sampling selected 242 and 485 patient-matched pairs from CDM and SHA databases, respectively. At 6 months post-index in longer-term vs short-term patiromer groups (P < 0.0001 for all differences shown), respective mean medical and prescription costs/charges were $42,000 vs $54,311 (-$12,311) and $6,816 vs $4,786 (+$2,030), respectively, for CDM patients and $75,147 vs $84,414 (-$9,267) and $4,689 vs $3,736 (+$953) for SHA patients. In the CDM database, medical costs were lower for longer-term vs short-term cohorts for end-stage renal disease services charges ($10,342 vs $14,976 [-$4,634]), inpatient charges ($15,789 vs $21,473 [-$5,684]), and office visit charges ($10,152 vs $13,152 [-$3,000]). Patient out-of-pocket costs ($658 vs $420 [+$238]) and total prescription charges ($6,158 vs $4,366 [+$1,792]) were higher for the longer-term cohort of CDM patients, with similar findings in the SHA dataset. Adherent, longer-term use of patiromer is associated with significantly lower medical costs offsetting higher prescription costs, driven by the largest changes in inpatient and clinic services at CDM and SHA, respectively. This illustrates an economic value of longer-term adherence to patiromer.

Impaired in vitro fertilization outcomes following testosterone treatment improve with washout in a mouse model of gender-affirming hormone treatment

The impact of gender-affirming testosterone on fertility is poorly understood, with ovarian histopathologic studies showing variable results, some with a detrimental effect on reproductive capacity and uncertain reversibility. Assisted reproductive outcome data are restricted to small case series that lack the ability to inform clinical practice guidelines and limit fertility preservation counseling for transgender and nonbinary individuals. This study aimed to determine the impact of current testosterone and testosterone washout on invitro fertilization outcomes in a mouse model for gender-affirming hormone treatment. We hypothesized that current or previous testosterone treatment would not affect invitro fertilization outcomes. C57BL/6N female mice (n=120) were assigned to 4 treatment groups: (1) current control, (2) current testosterone, (3) control washout, and (4) testosterone washout. Testosterone implants remained in situ for 6 or 12 weeks, representing the short- and long-term treatment arms, respectively. Current treatment groups underwent ovarian stimulation with implants in place, and washout treatment groups were explanted and had ovarian stimulation after 2 weeks. Oocytes were collected, fertilized, and cultured invitro, with one arm continuing to the blastocyst stage and the other having transfer of cleavage-stage embryos. Statistical analysis was performed using GraphPad Prism, version 9.0 and R statistical software, version 4.1.2, with statistical significance defined by P<.05. Current long-term testosterone treatment impaired invitro fertilization outcomes, with fewer mature oocytes retrieved (13.7±5.1 [standard deviation] vs 28.6±7.8 [standard deviation]; P<.0001) leading to fewer cleavage-stage embryos (12.1±5.1 vs 26.5±8.2; P<.0001) and blastocysts (10.0±3.2 vs 25.0±6.5; P<.0001). There was recovery of invitro fertilization outcomes following washout in the short-term treatment cohort, with incomplete reversibility in the long-term cohort. Testosterone did not negatively affect maturity, fertilization, or blastulation rates. In a mouse model of gender-affirming hormone treatment, testosterone negatively affected oocyte yield without affecting oocyte quality. Our findings suggest that testosterone reversibility is duration-dependent. These results demonstrate the feasibility of invitro fertilization without testosterone discontinuation while supporting a washout period for optimization of mature oocyte yield.

Association of CDK4 amplification with duration of response to bevacizumab in glioblastoma.

2026 Background: Bevacizumab remains the standard second line therapy in glioblastoma (GBM) with reported improved progression free survival, but not overall survival. We investigated a large clinico-genomic database of GBM patients treated with bevacizumab for molecular alterations associated with treatment outcome. Methods: Molecular profiles of GBM were tested by next-generation sequencing (NGS) of DNA (592 genes, NextSeq or whole-exome sequencing, Novaseq) and RNA (whole transcriptome sequencing, NovaSeq) at Caris Life Sciences (Phoenix, AZ). Gene amplification was determined by NGS with a threshold of &gt; = 6 copies. Real-world survival information was obtained from insurance claims data. Time-on-treatment (TOT) of bevacizumab was calculated from start to finish of treatment while post-bevacizumab overall survival (bevOS) from start of bevacizumab to last day of contact. Short-term (ST) and long-term (LT) responders were defined as those with TOT ≤6 months and ≥1 year, respectively. Kaplan-Meier estimates were calculated and significance was determined as p values of &lt; 0.05. For molecular comparisons, Fisher’s exact tests and Mann-Whiney U were used when appropriate. Results: Among the total of 383 ST and 107 LT patients identified, no significant difference in gender or age were seen. The LT cohort had significantly longer bevOS compared to the ST cohort (HR 0.27, [95% CI: 0.28-0.35], p &lt; 0.0001). Interestingly, CDK4 amplification was seen in 23% (18/78) of LT patients but only 7% (21/300, p = 0.0002) of ST. When investigating the total cohort of 498 GBM treated with bevacizumab, CDK4 amplified patients demonstrated significantly improved TOT compared to non-amplified (HR: 0.639, [0.48-0.85, p = 0.002]). Conversely, the ST cohort had significantly more EGFR amplifications than the LT cohort (43%, 130/300 vs. 19%, 15/79, p &lt; 0.0001). In the total bevacizumab-treated cohort, EGFR-amplified GBM had significantly worse TOT on bevacizumab than non-EGFR amplified GBM (HR 1.387, [1.15-1.67], p &lt; 0.001). No associations were seen in other alterations explored including PIK3CA mutation (HR = 0.81 [0.587-1.113], p = 0.2), EGFR mutation (HR: 1.209, [0.977-1.495], p = 0.1) or RAF1 (HR: 0.647, [0.318-1.317], p = 0.2). Conclusions: Using a large clinical genomic database with GBM subjected to comprehensive molecular profiling, we demonstrated that amplification of CDK4 and EGFR were associated with long-term and short-term responses to bevacizumab, respectively. This warrants further investigation in independent cohorts controlled for age and other prognostic factors. If confirmed, a genetic basis for treatment optimization may provide meaningful clinical outcomes.

Inter-Day Variation in the Fasting Plasma Lipopolysaccharide Concentration in the Morning Is Associated with Inter-Day Variation in Appetite in Japanese Males: A Short-Term Cohort Study

Injection of lipopolysaccharide (LPS), a product of gut bacteria, into the blood increases blood triglycerides and cortisol, an appetite-stimulating hormone. Meanwhile, small amounts of LPS derived from gut bacteria are thought to enter the bloodstream from the gut in daily basis. This study aimed to investigate the effect of LPS influx on appetite or lipid metabolism in humans in everyday life. We measured the fasting plasma LPS concentration before breakfast and the corresponding days' appetite and fat-burning markers for 10 days in four Japanese males (28-31 years) and analyzed the correlation of their inter-day variation. The LPS concentration was negatively correlated with fullness, and positively correlated with the carbohydrate intake. Against our hypothesis, the LPS concentration was positively correlated with the fasting breath acetone concentration, a fat-burning marker. There was a positive correlation between the LPS concentration and fasting body mass index (BMI), but the inter-day variation in BMI was slight. The results suggest that the LPS influx in everyday life is at least associated with appetite in the day.

Anti-Inflammatory Action of Antidepressants: Investigating the Longitudinal Effect of Antidepressants on White Blood Cell Count

Introduction: Antidepressants have documented anti-inflammatory effects on pro-inflammatory biomarkers. However, the long-term effects of antidepressants on inflammatory markers and the effects of different antidepressant classes on pro-inflammatory biomarkers are largely unexplored. Here, we evaluate the short- and long-term effects of all antidepressant classes on a clinical immune marker, white blood cell count (WBC). Methods: Using a retrospective study design, we extracted WBC count and prescription medications from electronic health records at Vanderbilt University Medical Center. We created a longitudinal model to evaluate the short- and long-term effects of these medications on WBC count. We validated our longitudinal model using two known anti-inflammatory medications, biologic immunosuppressants, and chemotherapy, and one medication class without known immunomodulatory properties, contraceptives. We used the longitudinal model to determine the effects of antidepressant use on WBC count stratified by drug class. Results: Biologic immunosuppressant and chemotherapy use was associated with decreased WBC count, but contraceptive use did not associate with changes in WBC count, validating our longitudinal modeling approach. All antidepressant classes were associated with decreased WBC count in the long-term cohorts. SSRI and atypical use also associated with decreased WBC count in the short-term cohort. Conclusions: Using electronic health record data, we show all antidepressant classes exhibit anti-inflammatory effects on a clinical immune marker, WBC count. Additionally, our results indicate that in some cases the anti-inflammatory effects of antidepressants persist over at least a 1-year time frame. Our work contributes to the immunomodulatory knowledge of antidepressants and motivates future studies investigating alternative therapeutic routes for antidepressants.

Fasting and weight loss: mobile application-based approach.

The purpose of this study was to investigate the efficacy of intermittent fasting (IF) guidance, delivered through a smartphone application, in terms of engagement and weight loss. We performed a retrospective chart-review study of all consecutive users with overweight or obesity of the DoFasting mobile application, which integrates IF solutions for people looking to lose weight. Users with overweight and obesity at the beginning of application use, who met the inclusion criteria (entered their gender, height, and starting weight; had more than one weight entry; used the app for at least a month; had at least one active day per week with valid app-related activities) and used the application for weight loss were included in the study. The final study cohort comprised 22,022 consecutive users. The short-term cohort comprised 17,221 users (8585 females and 8636 males), while 4801 users (2983 females and 1818 males) were in the long-term cohort. Long-term active users of the application lost a statistically significant amount of weight over the study period and lost more than inactive users did (2.2 [3.5] vs 1.4 [3.2], p < 0.0001; the results are shown in kilograms as medians with the interquartile range in brackets). Active and long-term users were also more likely to reduce their BMI class (p < 0.05) in comparison to non-active short-term users. A multiple regression model showed that the total length of use and active days were the most significant predictors of weight loss. In-app activities such as total fasting hours, weight logging, completing challenges, and providing feedback were also statistically significant predictors of weight loss with varying contributions. We found that the DoFasting mobile application that implements IF is an effective tool for weight loss if used actively and sufficiently. This retrospective chart review study was approved by BRANY IRB in January 2022 (study ID.: 22-08-034-939).

Three-dimensional position changes of unopposed molars before implant rehabilitation: a short-term retrospective cohort analysis

ObjectiveTo investigate the spatial changes of unopposed molars within the period between the antagonist extraction and the final implant restoration using data from cone beam computed tomography.MethodsA total of 59 patients with 68 unopposed molars were included in this study. Three-dimensional models reconstructed from cone beam computed tomography data before and after loss of the antagonist were superimposed to measure the spatial changes. The overeruption and tipping of target teeth were calculated by coordinate values.ResultsThe result of overeruption over the study period (9.2 ± 4.3 months) was expressed by two values: the mean overeruption of molar cups (0.432 mm) and the maximum overeruption of cusps (0.753 mm), which were statistically significant compared to the baseline level (p < 0.001). The average tipping was 1.717 degrees in the buccal direction.ConclusionsUnopposed molars displayed overeruption throughout the study period (9.2 ± 4.3 months), which indicates that the clinicians should pay attention to the possibilities of overeruption and make appropriate interventions in their clinical practice. The establishment of three-dimensional measuring methods using cone beam computed tomography data helps analyze spatial changes.

Salivary Gland Toxicity of PSMA-Targeted Radioligand Therapy with 177Lu-PSMA and Combined 225Ac- and 177Lu-Labeled PSMA Ligands (TANDEM-PRLT) in Advanced Prostate Cancer: A Single-Center Systematic Investigation.

Purpose: PSMA-targeted radioligand therapy (PRLT) is a promising treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). However, a high uptake of the radiopharmaceutical in the salivary glands (SG) can lead to xerostomia and becomes dose-limiting for 225Ac-PSMA-617. This study investigated the sialotoxicity of 177Lu-PSMA-I&T/-617 monotherapy and co-administered 225Ac-PSMA-617 and 177Lu-PSMA-617 (Tandem-PPRLT). Methods: Three patient cohorts, that had undergone 177Lu-PSMA-I&T/-617 monotherapy or Tandem-PRLT, were retrospectively analyzed. In a short-term cohort (91 patients), a xerostomia assessment (CTCAE v.5.0), a standardized questionnaire (sXI), salivary gland scintigraphy (SGS), and SG SUVmax and the metabolic volume (MV) on 68Ga-PSMA-11-PET/CT were obtained before and after two cycles of 177Lu-PSMA-I&T/-617. In a long-term cohort, 40 patients were similarly examined. In a Tandem cohort, the same protocol was applied to 18 patients after one cycle of Tandem-PRLT. Results: Grade 1 xerostomia in the short-term follow-up was observed in 22 (24.2%) patients with a worsening of sXI from 7 to 8 at (p < 0.05). In the long-term cohort, xerostomia grades 1 to 2 occurred in 16 (40%) patients. SGS showed no significant changes, but there was a decline of the MV of all SGs. After Tandem-PRLT, 12/18 (66.7%) patients reported xerostomia grades 1 to 2, and the sXI significantly worsened from 9.5 to 14.0 (p = 0.005), with a significant reduction in the excretion fraction (EF) and MV of all SGs. Conclusion: 177Lu-PSMA-I&T/-617 causes only minor SG toxicity, while one cycle of Tandem-PRLT results in a significant SG impairment. This standardized protocol may help to objectify and quantify SG dysfunction.

Intervention rates are low after direct discharge from the Edinburgh trauma triage clinic: Outcomes of 6,688 patients

AimThe Edinburgh Trauma Triage clinic (TTC) is an established form of Virtual Fracture clinic (VFC) that permits the direct discharge of simple, isolated fractures from the Emergency Department (ED). Small, short-term cohort studies of similar systems have been published, but to detect low rates of complications requires a large study sample and longer-term follow-up. This study details the outcomes of all patients with injuries suitable for a direct discharge protocol over a four-year period, reviewed at a minimum of three years after attendance. PatientsAll TTC records between February 2014 and December 2017 were collated from a prospective database. Fractures of the radial head, little finger metacarpal, fifth metatarsal, toe phalanges and mallet finger injuries were included. TTC outcome, including any deviations from a well-established direct discharge protocol, were noted. All records were re-assessed at a minimum of 36 months after TTC triage (mean 54 months) to ascertain which injuries attended the trauma clinic after initial discharge. Reasons for attendance, the source of referral and any subsequent surgical procedures were identified. ResultsThere were 6688 patients with fractures of the radial head (1861), little finger metacarpal (1621), fifth metatarsal (1916), toe phalanges (920) and mallet finger injuries (370). 298 (6%) patients were re-referred after direct discharge and attended trauma clinic at a mean time after injury of 11.9 weeks, of whom 11 (0.2%) underwent a surgical intervention. Serious adverse events, defined as those in which a patient may not have come to harm if early clinical review had been undertaken, occurred in 1 patient (0.01%). ConclusionIntervention after direct discharge of simple pre-defined injuries of the elbow, hand and foot is low. Within a TTC system, patients with these injuries can be safely discharged without routine follow-up.

EFFECTS OF MINERALOCORTICOID RECEPTOR ANTAGONISTS ON ALDOSTERONE TO RENIN RATIO IN PATIENTS WITH PRIMARY ALDOSTERONISM

Objective: Current guidelines recommend to withdraw interfering antihypertensive drugs before to perform a screening test for primary aldosteronism (PA). Recent studies suggested that diagnostic work-up of PA might be performed without withdrawing mineralocorticoid receptor antagonist (MRA) treatment in selected patients, especially when severe hypertension and hypokalemia are difficult to control. We designed a prospective study to evaluate the effects of MRA treatment on aldosterone to renin ratio (ARR) in patients with PA. Design and method: We prospectively recruited 121 patients with confirmed PA and started on canrenone treatment. Eighteen patients were enrolled in a short-term treatment cohort to assess the effects of MRA on aldosterone to renin ratio (ARR) and potassium after 2 and 8 weeks of canrenone therapy. One hundred and two patients were recruited in the long-term treatment cohort to evaluate the effects of canrenone on ARR after 2 to 12 months of MRA therapy. Results: Plasma renin activity and potassium displayed a significant increase, and ARR showed a significant reduction compared with baseline in patients with PA after MRA initiation. These effects were observed both after a short- and a long-term treatment with canrenone, and were progressively more significant after longer periods of therapy and with greater doses of MRA. We demonstrated that canrenone assumption severely impacts on the rate of false-negative screening tests for PA, which raised from 16.7% to 72.5% after 2 weeks and 7–12 months of MRA treatment, respectively. Conclusions: ARR testing for PA screening should not be performed under MRA therapy.

Evaluation of the Predictors for Unfavorable Clinical Outcomes of Degenerative Lumbar Spondylolisthesis After Lumbar Interbody Fusion Using Machine Learning.

BackgroundAn increasing number of geriatric patients are suffering from degenerative lumbar spondylolisthesis (DLS) and need a lumbar interbody fusion (LIF) operation to alleviate the symptoms. Our study was performed aiming to determine the predictors that contributed to unfavorable clinical efficacy among patients with DLS after LIF according to the support vector machine (SVM) algorithm.MethodsA total of 157 patients with single-segment DLS were recruited and performed LIF in our hospital from January 1, 2015 to October 1, 2020. Postoperative functional evaluation, including ODI and VAS were, performed, and endpoint events were defined as significant relief of symptom in the short term (2 weeks postoperatively) and long term (1 year postoperatively). General patient information and radiological data were selected and analyzed for statistical relationships with the endpoint events. The SVM method was used to establish the predictive model.ResultsAmong the 157 consecutive patients, a postoperative unfavorable clinical outcome was reported in 26 patients (16.6%) for a short-term cohort and nine patients (5.7%) for a long-term cohort. Based on univariate and multivariate regression analysis, increased disc height (DH), enlarged facet angle (FA), and raised lateral listhesis (LLS) grade were confirmed as the risk factors that hindered patients' short-term functional recovery. Furthermore, long-term functional recovery was significantly associated with DH alone. In combination with the SVM method, a prediction model with consistent and superior predictive performance was achieved with average and maximum areas under the receiver operating characteristic curve (AUC) of 0.88 and 0.96 in the short-term cohort, and 0.78 and 0.82 in the long-term cohort. The classification results of the discriminant analysis were demonstrated by the confusion matrix.ConclusionsThe proposed SVM model indicated that DH, FA, and LLS were statistically associated with a clinical outcome of DLS. These results may provide optimized clinical strategy for treatment of DLS.

Cognitive and gait outcomes after primary endoscopic third ventriculostomy in adults with chronic obstructive hydrocephalus.

The object of this study was to determine the short- and long-term efficacy of primary endoscopic third ventriculostomy (ETV) on cognition and gait in adults with chronic obstructive hydrocephalus. Patients were prospectively accrued through the Adult Hydrocephalus Clinical Research Network patient registry. Patients with previously untreated congenital or acquired obstructive hydrocephalus were included in this study. Gait velocity was assessed using a 10-m walk test. Global cognition was assessed with the Montreal Cognitive Assessment (MoCA). Only patients with documented pre- and post-ETV gait analysis and/or pre- and post-ETV MoCA were included. A total of 74 patients had undergone primary ETV, 42 of whom were analyzed. The remaining 32 patients were excluded, as they could not complete both pre- and post-ETV assessments. The mean age of the 42 patients, 19 (45.2%) of whom were female, was 51.9 ± 17.1 years (range 19-79 years). Most patients were White (37 [88.1%]), and the remainder were Asian. Surgical complications were minor. Congenital etiologies occurred in 31 patients (73.8%), with aqueductal stenosis in 23 of those patients (54.8%). The remaining 11 patients (26.2%) had acquired cases. The gait short-term follow-up cohort (mean 4.7 ± 4.1 months, 35 patients) had a baseline median gait velocity of 0.9 m/sec (IQR 0.7-1.3 m/sec) and a post-ETV median velocity of 1.3 m/sec (IQR 1.1-1.4 m/sec). Gait velocity significantly improved post-ETV with a median within-patient change of 0.3 m/sec (IQR 0.0-0.6 m/sec, p < 0.001). Gait velocity improvements were sustained in the long term (mean 14 ± 2.8 months, 12 patients) with a baseline median velocity of 0.7 m/sec (IQR 0.6-1.3 m/sec), post-ETV median of 1.3 m/sec (IQR 1.1-1.7 m/sec), and median within-patient change of 0.4 m/sec (IQR 0.2-0.6 m/sec, p < 0.001). The cognitive short-term follow-up cohort (mean 4.6 ± 4.0 months, 38 patients) had a baseline median MoCA total score (MoCA TS) of 24/30 (IQR 23-27) that improved to 26/30 (IQR 24-28) post-ETV. The median within-patient change was +1 point (IQR 0-2 points, p < 0.001). However, this change is not clinically significant. The cognitive long-term follow-up cohort (mean 14 ± 3.1 months, 15 patients) had a baseline median MoCA TS of 23/30 (IQR 22-27), which improved to 26/30 (IQR 25-28) post-ETV. The median within-patient change was +2 points (IQR 1-3 points, p = 0.007), which is both statistically and clinically significant. Primary ETV can safely improve symptoms of gait and cognitive dysfunction in adults with chronic obstructive hydrocephalus. Gait velocity and global cognition were significantly improved, and the worsening of either was rare following ETV.

Predicting the pulmonary effects of long-term e-cigarette use: are the clouds clearing?

Commercially available since 2007, e-cigarettes are a popular electronic delivery device of ever-growing complexity. Given their increasing use by ex-smokers, smokers and never-smokers, it is important to evaluate evidence of their potential pulmonary effects and predict effects of long-term use, since there has been insufficient time to study a chronic user cohort. It is crucial to evaluate indicators of harm seen in cigarette use, and those potentially unique to e-cigarette exposure. Evaluation must also account for the vast variation in e-cigarette devices (now including at least five generations of devices) and exposure methods used in vivo and in vitroThus far, short-term use cohort studies, combined with in vivo and in vitro models, have been used to probe for the effects of e-cigarette exposure. The effects and mechanisms identified, including dysregulated inflammation and decreased pathogen resistance, show concerning overlaps with the established effects of cigarette smoke exposure. Additionally, research has identified a signature of dysregulated lipid processing, which is unique to e-cigarette exposure.This review will evaluate the evidence of pulmonary effects of, and driving mechanisms behind, e-cigarette exposure, which have been highlighted in emerging literature, and highlight the gaps in current knowledge. Such a summary allows understanding of the ongoing debate into e-cigarette regulation, as well as prediction and potential mitigation of future problems surrounding e-cigarette use.

Measuring symptoms severity in carpal tunnel syndrome: score agreement and responsiveness of the Atroshi-Lyr\xe9n 6-item symptoms scale and the Boston symptom severity scale

PurposeTo assess score agreement between the Atroshi-Lyrén 6-item symptoms scale and the Boston 11-item symptom severity scale and compare their responsiveness in patients with carpal tunnel syndrome before and after carpal tunnel release surgery.MethodsThis prospective cohort study included 3 cohorts that completed the A-L and Boston scales (conventional score 1–5) on the same occasion: a preoperative and short-term postoperative cohort (212 patients), a mid-term postoperative cohort (101 patients), and a long-term postoperative cohort (124 patients). Agreement was assessed with Lin’s concordance correlation coefficient and Passing-Bablok regression analysis. Analyses using item response theory were conducted on responses from the preoperative/short-term postoperative cohort including testing of item infit/outfit. Reliability was assessed with Cronbach alpha. Overall and sex-specific effect sizes were calculated using Cohen’s d.ResultsLin’s CCCs were high (0.81–0.91). Passing-Bablok analysis showed constant and proportional differences in all cohorts except preoperative to short-term postoperative change. Both scales showed high reliability (alpha, 0.88–0.93). The IRT-based analyses showed infit/outfit values within the desired range. With IRT-based scoring, the A-L scale had significantly higher responsiveness than the Boston scale, overall (d, 2.02 vs 1.59), in women (d, 2.22 vs 1.77) and in men (d, 1.74 vs 1.36).ConclusionThe Atroshi-Lyrén 6-item symptoms scale and the Boston 11-item symptom severity scale show good agreement but are not equivalent in measuring CTS-related symptoms severity. When using IRT-based scoring, the Atroshi-Lyrén scale demonstrated significantly higher responsiveness.