Intramedullary Threaded Nail Fixation of Distal Ulnar Fractures: The Surgical Technique and Case Series.

BACKGROUND:  To describe the surgical technique of non-compressive intramedullary threaded nail (IMTN) fixation of distal ulnar neck fractures and present the clinical and radiographic outcomes of four patients treated with this novel technique. METHODS: At a single Level 1 Trauma Center, a retrospective review was conducted for patients with distal ulnar neck fractures treated with retrograde IMTN between 2022 and 2024. Exclusion criteria included inadequate follow-up. A single surgeon performed all procedures using percutaneous retrograde IMTN fixation through the central disc of the triangular fibrocartilage complex (TFCC). Patients initiated a range of motion (ROM) protocol two weeks post-operatively. Post-operative radiographic images were used to calculate the ratio of IMTN diameter to the distal ulnar medullary isthmus diameter proximal to the fracture site. Radiographic changes in displacement, angulation, and ulnar variance were calculated between the first and last follow-up radiographs. Functional outcomes including grip strength and ROM were collected. RESULTS: Four patients with distal ulnar neck fractures were treated with retrograde IMTN between 2022 and 2024. They were followed for a minimum of three months post-operatively. All were female with an average age of 65 years. All distal ulna fractures were associated with operatively treated intraarticular distal radius fractures. All patients were treated with 75 mm length and 4.5 mm diameter IMTNs. IMTN-to-Isthmus ratio was greater than 60% in all cases. Average radiographic displacement and angulation were unchanged at the final follow-up. The average ulnar variance increased by 1.2 mm. At the final follow-up, there were no post-operative complications. No cases demonstrated ulnar-sided wrist pain, nonunion, or required revision surgery. CONCLUSIONS: Retrograde IMTN fixation is a novel surgical technique for the treatment of distal ulnar neck fractures. We found limited but promising post-operative radiographic and functional outcomes in our patients without reported ulnar-sided wrist pain, nonunion, or need for hardware removal.

Translating the Interplay of Cognition and Physical Performance in COPD and Interstitial Lung Disease: Meeting Report and Literature Review.

TOPIC IMPORTANCE: Cognitive and physical limitations are common in individuals with chronic lung diseases, but their interactions with physical function and activities of daily living are not well characterized. Understanding these interactions and potential contributors may provide insights on disability and enable more tailored rehabilitation strategies. REVIEW FINDINGS: This review summarizes a 2-day meeting of patient partners, clinicians, researchers, and lung associations to discuss the interplay between cognitive and physical function in people with chronic lung diseases. This report covers four areas: (1) cognitive-physical limitations in patients with chronic lung diseases; (2) cognitive assessments; (3) strategies to optimize cognition and motor control; and (4) future research directions. Cognitive and physical impairments have multiple effects on quality of life and daily function. Meeting participants acknowledged the need for a standardized cognitive assessment to complement physical assessments in patients with chronic lung diseases. Dyspnea, fatigue, and age were recognized as important contributors to cognition that can affect motor control and daily physical function. Pulmonary rehabilitation was highlighted as a multidisciplinary strategy that may improve respiratory and limb motor control through neuroplasticity and has the potential to improve physical function and quality of life. SUMMARY: There was consensus that cognitive function and the cognitive interference of dyspnea in people with chronic lung diseases contribute to motor control impairments that can negatively affect daily function, which may be improved with pulmonary rehabilitation. The meeting generated several key research questions related to cognitive-physical interactions in individuals with chronic lung diseases.

Continuous measurements of respiratory muscle blood flow & oxygen consumption using non-invasive FD-NIRS & DCS.

Prior studies of muscle blood flow and muscle specific oxygen consumption have required invasive injection of dye and Magnetic Resonance Imaging, respectively. Such measures have limited utility for continuous monitoring of the respiratory muscles. Frequency domain near-infrared spectroscopy and diffuse correlation spectroscopy (FD-NIRS & DCS) can provide continuous surrogate measures of blood flow index (BFi) and metabolic rate of oxygen consumption (MRO2). This study aimed to validate sternocleidomastoid FD-NIRS & DCS outcomes against electromyography (EMG) and mouth pressure (Pm) during incremental inspiratory threshold loading (ITL). Six females and six male healthy adults (mean±SD; 30±7 years, maximum inspiratory pressure 118±61 cmH2O) performed incremental ITL starting at low loads (8±2 cmH2O) followed by 50g increments every two minutes until task failure. FD-NIRS & DCS continuously measured sternocleidomastoid oxygenated and deoxygenated hemoglobin+myoglobin (oxy/deoxy[Hb+Mb]), tissue saturation of oxygen (StO2), BFi, and MRO2. Ventilatory parameters including inspiratory Pm were also evaluated. Pm increased during incremental ITL (P<0.05), reaching -47[-74 - -34] cmH2O (median[25%-75%IQR] at task failure. Ventilatory parameters were constant throughout ITL (all P>0.05). Sternocleidomastoid BFi and MRO2 increased from the start of the ITL (both P<0.05). Deoxy[Hb+Mb] increased close to task failure, concomitantly with a constant increase in MRO2, and decreased StO2. Sternocleidomastoid deoxy[Hb+Mb], BFi, StO2 and MRO2 obtained during ITL via FD-NIRS & DCS correlated with sternocleidomastoid EMG (all P<0.05). In healthy adults, FD-NIRS & DCS can provide continuous surrogate measures of respiratory BFi and MRO-2. Increasing sternocleidomastoid oxygen consumption near task failure was associated with increased oxygen extraction and reduced tissue saturation.

Online resources as a source of information for exercise and physical activity in solid organ transplant recipients.

Introduction: Exercise training post-transplant has been shown to improve physical function and quality of life in solid organ transplant (SOT) recipients. Online resources in the form of websites and videos are commonly used to provide education and instruction on exercise and physical activity in SOT; however, the content and quality of these online resources has not been evaluated. Methods: The first 200 websites and videos identified on Google and YouTube using the English search term "exercise and physical activity in solid organ transplantation" were analyzed. Website and video content was evaluated based on 25 key components of exercise and physical activity in SOT as described in established exercise program recommendations. Website and video quality was determined using DISCERN, Global Quality Scale (GQS), and Patient Education Materials and Assessment Tool (PEMAT; threshold for which material is deemed understandable or actionable is >70%). Parametric and non-parametric tests were used to assess website and video characteristics, content, and quality metrics. Results: Forty-nine unique SOT websites (n = 15) and videos (n = 34) were identified, with the two most common categories being foundation/advocacy organizations and scientific resources. The average reading grade level of websites was 13 ± 3. Website and video content scores varied significantly (websites 11.3 ± 6.4; videos 8.4 ± 5.3). DISCERN total score and GQS score were low (median range for DISCERN 2.5-3.0; median for GQS 2.0 for both websites and videos, out of 5). PEMAT understandability and actionability scores were also low across websites and videos (mean range 57%-67% and 47%-65%, respectively). Foundation/advocacy websites had higher content and quality scores compared to scientific organizations and news/media articles. Conclusions: To our knowledge, this is the first comprehensive assessment of online content and quality of website and video resources on physical activity and exercise in adult SOT recipients. There were a limited number of online English patient-directed resources related to physical activity in SOT, most of which only partly captured items outlined in consensus exercise program recommendations and were of low quality and understandability and actionability. This work provides important insight to the English-speaking transplant community on the current state of online exercise health information and provides future direction for resource development.

Outcomes Following Surgical Fixation of Distal Radius Fractures in Patients With Chronic Kidney Disease.

Purpose: Moderate-to-severe chronic kidney disease (CKD, stages III-IV) and end-stage renal disease (ESRD or CKD stage V) are known to be independent risk factors for fragility fracture. Altered bone and mineral metabolism contributes to greater complications and mortality rates in the setting of fractures, although most existing literature is limited to hip fractures. We hypothesized that patients with moderate-to-severe CKD or ESRD would have greater complication rates after surgical treatment of distal radius fractures compared with those without CKD. Methods: We retrospectively identified all patients at a level 1 trauma center between 2008 and 2018 who had a diagnosis of stage III-IV CKD or ESRD at the time of operative fixation of a distal radius fracture. We recorded demographic data, comorbidities, and surgical complications. Data for readmissions within 90 days and 1-year mortality were collected. A 2:1 sex-matched control group without CKD who underwent distal radius fixation was selected for comparison, with age-adjusted analysis. Results: A total of 32 patients with CKD (78.1% CKD stage III/IV, 21.9% ESRD) and 62 without CKD were identified. The mean age was 67 ± 12 years in the CKD group and 55 ± 15 years in the control group. The CKD group had a higher Charlson Comorbidity Index (5.7 vs 2.0). Surgical complication rate in the CKD group was 12.5% (12.0% CKD III/IV; 14.3% ESRD). Neither early nor late surgical complication rates were statistically different from those in patients without CKD. Reoperation rate as well as 30- and 90-day readmission rates were similar between groups. Overall, 1-year mortality was greater in the CKD group (9.4% vs 0%). Conclusions: Surgical complications and readmission rates are similar in patients with and without CKD after distal radius fracture fixation. However, 1-year mortality rate is significantly higher after distal radius fixation in patients with moderate-to-severe CKD or ESRD. Type of study/level of evidence: Prognostic IIIa.

Outcomes Following Surgical Fixation of Upper Extremity Fractures in Patients with Chronic Kidney Disease.

Purpose: Moderate to severe (stage III-IV) chronic kidney disease (CKD) and end stage renal disease (ESRD) have been shown to be independent risk factors for sustaining a fragility fracture. High rates of complications and mortality are associated with fracture fixation in patients with CKD, but existing literature is limited. It is unknown how CKD stage III-IV or ESRD affects outcomes in upper-extremity fractures. We hypothesize that patients with CKD stage III-IV or ESRD will have high complication rates after surgical fixation of upper extremity fractures. Methods: We identified all patients between 2008 and 2018 who underwent operative fixation of an upper extremity fracture proximal to the distal radius with a diagnosis of CKD stage III-IV or ESRD at the time of injury. Those with an acute kidney injury at the time of injury or a history of a kidney transplant were excluded. Demographics, medical complications, and surgical complications were collected retrospectively. Data on readmissions within 90 days and mortality within 1 year were also collected. Results: Thirty-five patients were identified. Three patients had ESRD. Fractures included two clavicle, twelve proximal humerus, one humeral shaft, ten distal humerus, five olecranon, two ulnar shaft, one radial shaft, and two both-bone forearm fractures. In total, 91.4% of fractures were closed injuries. Surgical complications occurred in 40% of patients. The reoperation rate was 11.4%, and all cases of reoperation involved hardware removal. The all-cause 90-day readmission rate was 34.3%. The 1-year mortality rate was 8.6%. Conclusions: Surgical complications occurred in 40% of patients with CKD stage III-IV or ESRD who underwent fixation for an upper extremity fracture. It is important to counsel these patients regarding their high risk for complications. Further research is needed to investigate and identify how to mitigate risk. Type of study/level of evidence: Prognostic IV.

Clinical implications of frailty assessed in hospitalized patients with acute-exacerbation of interstitial lung disease.

BACKGROUND: Approximately 50% of patients with interstitial lung disease (ILD) experience frailty, which remains unexplored in acute exacerbations of ILD (AE-ILD). A better understanding may help with prognostication and resource planning. We evaluated the association of frailty with clinical characteristics, physical function, hospital outcomes, and post-AE-ILD recovery. METHODS: Retrospective cohort study of AE-ILD patients (01/2015-10/2019) with frailty (proportion ≥0.25) on a 30-item cumulative-deficits index. Frail and non-frail patients were compared for pre- and post-hospitalization clinical characteristics, adjusted for age, sex, and ILD diagnosis. One-year mortality, considering transplantation as a competing risk, was analysed adjusting for age, frailty, and Charlson Comorbidity Index (CCI). RESULTS: 89 AE-ILD patients were admitted (median: 67 years, 63% idiopathic pulmonary fibrosis). 31 were frail, which was associated with older age, greater CCI, lower 6-min walk distance, and decreased independence pre-hospitalization. Frail patients had more major complications (32% vs 10%, p = .01) and required more multidisciplinary support during hospitalization. Frailty was not associated with 1-year mortality (HR: 0.97, 95%CI: [0.45-2.10]) factoring transplantation as a competing risk. CONCLUSIONS: Frailty was associated with reduced exercise capacity, increased comorbidities and hospital complications. Identifying frailty may highlight those requiring additional multidisciplinary support, but further study is needed to explore whether frailty is modifiable with AE-ILD.

Combined frequency domain near-infrared spectroscopy and diffuse correlation spectroscopy system for comprehensive metabolic monitoring of inspiratory muscles during loading.

Significance: Mechanical ventilation (MV) is a cornerstone technology in the intensive care unit as it assists with the delivery of oxygen in critically ill patients. The process of weaning patients from MV can be long and arduous and can lead to serious complications for many patients. Despite the known importance of inspiratory muscle function in the success of weaning, current clinical standards do not include direct monitoring of these muscles. Aim: The goal of this project was to develop and validate a combined frequency domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) system for the noninvasive characterization of inspiratory muscle response to a load. Approach: The system was fabricated by combining a custom digital FD-NIRS and DCS system. It was validated via liquid phantom titrations and a healthy volunteer study. The sternocleidomastoid (SCM), an accessory muscle of inspiration, was monitored during a short loading period in fourteen young, healthy volunteers. Volunteers performed two different respiratory exercises, a moderate load and a high load, which consisted of a one-minute baseline, a one-minute load, and a six-minute recovery period. Results: The system has low crosstalk between absorption, reduced scattering, and flow when tested in a set of liquid titrations. Faster dynamics were observed for changes in blood flow index (BFi), and metabolic rate of oxygen (MRO2) compared with hemoglobin + myoglobin (Hb+Mb) based parameters after the onset of loads in males. Additionally, larger percent changes in BFi, and MRO2 were observed compared with Hb+Mb parameters in both males and females. There were also sex differences in baseline values of oxygenated Hb+Mb, total Hb+Mb, and tissue saturation. Conclusions: The dynamic characteristics of Hb+Mb concentration and blood flow were distinct during loading of the SCM, suggesting that the combination of FD-NIRS and DCS may provide a more complete picture of inspiratory muscle dynamics.

A Comparison of Patient Characteristics and Outcomes Between Patients Receiving Flexor Digitorum Superficialis Slip Excision or Isolated A1 Pulley Release for Trigger Finger.

PURPOSE: Resection of the radial or ulnar slip of the flexor digitorum superficialis (FDS) tendon is a known treatment option for persistent trigger finger. Risk factors for undergoing FDS slip excision are unclear. We hypothesized that patients who underwent A1 pulley release with FDS slip excision secondary to persistent triggering would have a higher comorbidity burden compared to those receiving A1 pulley release alone. METHODS: We identified all adult patients who underwent A1 pulley release with FDS slip excision because of persistent triggering either intraoperatively or postoperatively from 2018 to 2023. We selected a 3:1 age- and sex-matched control group who underwent isolated A1 pulley release. Charts were retrospectively reviewed for demographics, selected comorbidities, trigger finger history, and postoperative course. We performed multivariable logistic regression to assess the probability of FDS slip excision after adjusting for several variables that were significant in bivariate comparisons. RESULTS: We identified 48 patients who underwent A1 pulley release with FDS slip excision and 144 controls. Our multivariable model showed that patients with additional trigger fingers and a preoperative proximal interphalangeal (PIP) joint contracture were significantly more likely to undergo FDS slip excision. CONCLUSIONS: Patients who underwent A1 pulley release with FDS slip excision were significantly more likely to have multiple trigger fingers or a preoperative PIP joint contracture. Clinicians should counsel patients with these risk factors regarding the potential for FDS slip excision in addition to A1 pulley release to alleviate triggering of the affected digit. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

EELS: Autonomous snake-like robot with task and motion planning capabilities for ice world exploration.

Ice worlds are at the forefront of astrobiological interest because of the evidence of subsurface oceans. Enceladus in particular is unique among the icy moons because there are known vent systems that are likely connected to a subsurface ocean, through which the ocean water is ejected to space. An existing study has shown that sending small robots into the vents and directly sampling the ocean water is likely possible. To enable such a mission, NASA's Jet Propulsion Laboratory is developing a snake-like robot called Exobiology Extant Life Surveyor (EELS) that can navigate Enceladus' extreme surface and descend an erupting vent to capture unaltered liquid samples and potentially reach the ocean. However, navigating to and through Enceladus' environment is challenging: Because of the limitations of existing orbital reconnaissance, there is substantial uncertainty with respect to its geometry and the physical properties of the surface/vents; communication is limited, which requires highly autonomous robots to execute the mission with limited human supervision. Here, we provide an overview of the EELS project and its development effort to create a risk-aware autonomous robot to navigate these extreme ice terrains/environments. We describe the robot's architecture and the technical challenges to navigate and sense the icy environment safely and effectively. We focus on the challenges related to surface mobility, task and motion planning under uncertainty, and risk quantification. We provide initial results on mobility and risk-aware task and motion planning from field tests and simulated scenarios.

Sex related difference in postoperative pain and opioid use following posterior spinal fusion for adolescent idiopathic scoliosis.

PURPOSE: This project aims to evaluate the relationship between biological sex and postoperative pain and in patients receiving posterior spinal fusion for adolescent idiopathic scoliosis. METHODS: This is a retrospective study of patients (n=137) aged 10-17 receiving posterior spinal fusion for adolescent idiopathic scoliosis between 01/2018 and 09/2022. Each patient received surgery by the same pediatric orthopedic surgeon with identical postoperative pain management regimen at a children's hospital or a tertiary referral center with a pediatric spine program. RESULTS: There were no significant differences in any background characteristics between the male and female patients, including age, BMI, number of levels fused, preoperative degree of scoliosis, and length of surgery and anesthesia (p>0.05). There were no differences in amount given of any intraoperative medications, nor in amount of postoperative scheduled analgesics (p>0.05). Female patients demonstrated higher average pain scores on Visual Analogue Scale evaluations during the first 24 hours postoperatively (5.0 vs 3.6, p<0.0001), 24-48 hours postoperatively (4.9 vs 4.0, p=0.03), and at the first physical therapy evaluation (5.3 vs 3.8, p<0.001). These patients received significantly greater amounts of morphine milligram equivalents in the first 24 hours postoperatively (42.2 vs 31.5, p=0.01) and for the hospitalization in total (63.8 vs 51.3, p=0.048). There was no difference in hours until hospital discharge (44.3 vs 42.6, p=0.62) nor until first ambulation (20.1 vs 21.3, p=0.24) between the female and male patients. CONCLUSION: The influence of biopsychosocial factors on postoperative pain in adolescents is complex. This study adds to the existing pool of literature suggesting differences in pain perception between adolescent female and male patients. Female patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis may benefit from increased preoperative counseling and more aggressive intra- and postoperative pain management regimens.

Slimmer's Palsy Following Weight Loss Associated With Metastatic Breast Cancer: A Case Report.

Common peroneal neuropathy (CPN), also known as Slimmer's Palsy, is an isolated peripheral neuropathy typically associated with rapid weight loss resulting in loss of adipose tissue and subsequent nerve compression at the fibular head and is up to three times more common in individuals with malignancy. In this case report, we describe the diagnosis of CPN in a 54-year-old female with a 2.5-month history of atraumatic left foot drop and left ankle paresthesias, preceded by a 35-40 pound weight loss over the prior 3.5 month period in the setting of metastatic breast cancer.

The Pediatric Data Science and Analytics Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network: Use of Supervised Machine Learning Applications in Pediatric Critical Care Medicine Research.

OBJECTIVE: Perform a scoping review of supervised machine learning in pediatric critical care to identify published applications, methodologies, and implementation frequency to inform best practices for the development, validation, and reporting of predictive models in pediatric critical care. DESIGN: Scoping review and expert opinion. SETTING: We queried CINAHL Plus with Full Text (EBSCO), Cochrane Library (Wiley), Embase (Elsevier), Ovid Medline, and PubMed for articles published between 2000 and 2022 related to machine learning concepts and pediatric critical illness. Articles were excluded if the majority of patients were adults or neonates, if unsupervised machine learning was the primary methodology, or if information related to the development, validation, and/or implementation of the model was not reported. Article selection and data extraction were performed using dual review in the Covidence tool, with discrepancies resolved by consensus. SUBJECTS: Articles reporting on the development, validation, or implementation of supervised machine learning models in the field of pediatric critical care medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 5075 identified studies, 141 articles were included. Studies were primarily (57%) performed at a single site. The majority took place in the United States (70%). Most were retrospective observational cohort studies. More than three-quarters of the articles were published between 2018 and 2022. The most common algorithms included logistic regression and random forest. Predicted events were most commonly death, transfer to ICU, and sepsis. Only 14% of articles reported external validation, and only a single model was implemented at publication. Reporting of validation methods, performance assessments, and implementation varied widely. Follow-up with authors suggests that implementation remains uncommon after model publication. CONCLUSIONS: Publication of supervised machine learning models to address clinical challenges in pediatric critical care medicine has increased dramatically in the last 5 years. While these approaches have the potential to benefit children with critical illness, the literature demonstrates incomplete reporting, absence of external validation, and infrequent clinical implementation.

Intermittent neck flexion induces greater sternocleidomastoid deoxygenation than inspiratory threshold loading.

PURPOSE: To compare deoxygenation of the sternocleidomastoid, scalenes, and diaphragm/intercostals (Dia/IC) during submaximal intermittent neck flexion (INF) versus submaximal inspiratory threshold loading (ITL) in healthy adults. METHODS: Fourteen participants performed a randomized, cross-over, repeated measures design. After evaluation of maximal inspiratory pressures (MIP) and maximum voluntary contraction (MVC) for isometric neck flexion, participants were randomly assigned to submaximal ITL or INF until task failure. At least 2 days later, they performed the submaximal exercises in the opposite order. ITL or INF targeted 50 ± 5% of the MIP or MVC, respectively, until task failure. Near-infrared spectroscopy (NIRS) was applied to evaluate changes of deoxy-hemoglobin (ΔHHb), oxy-hemoglobin (ΔO2Hb), total hemoglobin (ΔtHb), and tissue saturation of oxygen (StO2) of the sternocleidomastoid, scalenes, and Dia/IC. Breathlessness and perceived exertion were evaluated using Borg scales. RESULTS: Initially during INF, sternocleidomastoid HHb slope was greatest compared to the scalenes and Dia/IC. At isotime (6.5-7 min), ΔtHb (a marker of blood volume) and ΔO2Hb of the sternocleidomastoid were higher during INF than ITL. Sternocleidomastoid HHb, O2Hb, and tHb during INF also increased at quartile and task failure timepoints. In contrast, scalene ΔO2Hb was higher during ITL than INF at isotime. Further, Dia/IC O2Hb and tHb increased during ITL at the third quartile and at task failure. Borg scores were lower at task failure during INF compared to ITL. CONCLUSION: Intermittent INF induces significant metabolic activity of the sternocleidomastoid and a lower perception of effort, which may provide an alternative inspiratory muscle training approach for mechanically ventilated patients.

A multi-cohort phase 1b trial of rituximab in combination with immunotherapy doublets in relapsed/refractory follicular lymphoma.

Antibodies targeting PD-1 or 4-1BB achieve objective responses in follicular lymphoma (FL), but only in a minority of patients. We hypothesized that targeting multiple immune receptors could overcome immune resistance and increase response rates in patients with relapsed/refractory FL. We therefore conducted a phase 1b trial testing time-limited therapy with different immunotherapy doublets targeting 4-1BB (utomilumab), OX-40 (ivuxolimab), and PD-L1 (avelumab) in combination with rituximab among patients with relapsed/refractory grade 1-3A FL. Patients were enrolled onto 2 of 3 planned cohorts (cohort 1 - rituximab/utomilumab/avelumab; cohort 2 - rituximab/ivuxolimab/utomilumab). 3+3 dose escalation was followed by dose expansion at the recommended phase 2 dose (RP2D). Twenty-four patients were enrolled (16 in cohort 1 and 9 in cohort 2, with one treated in both cohorts). No patients discontinued treatment due to adverse events and the RP2D was the highest dose level tested in both cohorts. In cohort 1, the objective and complete response rates were 44% and 19%, respectively (50% and 30%, respectively, at RP2D). In cohort 2, no responses were observed. The median progression-free survivals in cohorts 1 and 2 were 6.9 and 3.2 months, respectively. In cohort 1, higher density of PD-1+ tumor-infiltrating T-cells on baseline biopsies and lower density of 4-1BB+ and TIGIT+ T-cells in on-treatment biopsies were associated with response. Abundance of Akkermansia in stool samples was also associated with response. Our results support a possible role for 4-1BB agonist therapy in FL and suggest that features of the tumor microenvironment and stool microbiome may be associated with clinical outcomes (NCT03636503).

A combined frequency domain near infrared spectroscopy and diffuse correlation spectroscopy system for comprehensive metabolic monitoring of inspiratory muscles during loading.

Significance: Mechanical ventilation (MV) is a cornerstone technology in the intensive care unit as it assists with the delivery of oxygen in critical ill patients. The process of weaning patients from MV can be long, and arduous and can lead to serious complications for many patients. Despite the known importance of inspiratory muscle function in the success of weaning, current clinical standards do not include direct monitoring of these muscles. Aim: The goal of this project was to develop and validate a combined frequency domain near infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) system for the noninvasive characterization of inspiratory muscle response to a load. Approach: The system was fabricated by combining a custom digital FD-NIRS and DCS system. It was validated via liquid phantom titrations and a healthy volunteer study. The sternocleidomastoid (SCM), an accessory muscle of inspiration, was monitored during a short loading period in fourteen young healthy volunteer. Volunteers performed two different respiratory exercises, a moderate and high load, which consisted of a one-minute baseline, a one-minute load, and a six-minute recovery period. Results: The system has low crosstalk between absorption, reduced scattering, and flow when tested in a set of liquid titrations. Faster dynamics were observed for changes in blood flow index (BFi), and metabolic rate of oxygen (MRO2) compared to hemoglobin + myoglobin (Hb+Mb) based parameters after the onset of loads in males. Additionally, larger percent changes in BFi, and MRO2 were observed compared to Hb+Mb parameters in both males and females. There were also sex differences in baseline values of oxygenated Hb+Mb, total Hb+Mb, and tissue saturation. Conclusion: The dynamic characteristics of Hb+Mb concentration and blood flow were distinct during loading of the SCM, suggesting that the combination of FD-NIRS and DCS may provide a more complete picture of inspiratory muscle dynamics.

Physical activity in idiopathic pulmonary fibrosis: Longitudinal change and minimal clinically important difference.

BACKGROUND AND OBJECTIVE: Reference values of physical activity to interpret longitudinal changes are not available in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to define the minimal clinical important difference (MCID) of longitudinal changes in physical activity in patients with IPF. METHODS: Using accelerometry, physical activity (steps per day) was measured and compared at baseline and 6-months follow-up in patients with IPF. We calculated MCID of daily step count using multiple anchor-based and distribution-based methods. Forced vital capacity and 6-minute walk distance were applied as anchors in anchor-based methods. Effect size and standard error of measurement were used to calculate MCID in distribution-based methods. RESULTS: One-hundred and five patients were enrolled in the study (mean age: 68.5 ± 7.5 years). Step count significantly decreased from baseline to 6-months follow-up (-461 ± 2402, p = .031). MCID calculated by anchor-based and distribution-based methods ranged from 570-1358 steps. CONCLUSION: Daily step count significantly declined over 6-months in patients with IPF. MCID calculated by multiple anchor-based and distribution-based methods was 570 to 1358 steps/day. These findings contribute to interpretation of the longitudinal changes of physical activity that will assist its use as a clinical and research outcome in patients with IPF.

The interrelationship between lower limb movement, muscle activity, and joint moment during half squat and gait.

Joint moment is the resultant force of limb movements. However, estimation methods for joint moments using surface electromyography frequently use joint angles instead of limb angles. The limb angle in joint moment estimation using electromyography could clarify the effects of muscle activity on the limbs: acceleration, deceleration, or stabilization. No study has quantified the comprehensive relationship between limb movement, muscle activity, and joint moment. This study aimed to determine the influencing factors for ankle-joint moment and knee-joint moment in the sagittal plane among muscle activities and parameters related to limb movements during half squat and gait. This study included 29 healthy adults (16 female participants, 21.1 ± 2.09 years). Using inertial measurement units, thigh, shank, and foot inclination angles and angular accelerations were calculated as the parameters of limb movements. Muscle activations of the biceps femoris long head, rectus femoris, gastrocnemius, and tibialis anterior were measured. Ankle joint moment and knee-joint moment were measured using a three-dimensional motion capture system and two force plates. Regression models showed high accuracy in measuring ankle-joint moment during a half squat and gait (R2f = 0.92, 0.97, respectively) and knee-joint moment during a half squat (R2f = 0.98), but not knee-joint moment during gait (R2f = 0.63). However, only a maximum of five parameters were selected from muscle activities and limb angular information. Tibialis anterior and gastrocnemius activity were the largest contributors to ankle-joint moment during a half squat and gait, respectively, while muscle activities were not directly reflected in the knee-joint moment during either movement. Consideration of the interrelationships among limb movement, muscle activity, and joint moment is required when adjusting joint movements according to the target and aim of the therapeutic interventions.

Serotonin Syndrome Triggered by an Interaction Between Opioid Analgesics and Cobicistat: A Challenging Diagnostic Case Report.

Serotonin syndrome is a clinically diagnosed disorder that may occur secondary to medications that increase the release of endogenous serotonin, impair the reuptake of serotonin from the synaptic cleft, are direct serotonin receptor agonists, or increase the sensitivity of the postsynaptic serotonin receptor. In this case report, we describe the diagnosis of serotonin syndrome in a 60-year-old immunocompromised male. This case is unique, as many of the medications associated with the development of serotonin syndrome in this patient are not typically thought of as being associated with serotonin syndrome, though, in this clinical context, they combined to produce a profound pro-serotonergic effect.