Spatial and Temporal Relationships Between Atrophy and Hypometabolism in Behavioral-Variant Frontotemporal Dementia.

PURPOSE: Individuals with behavioral-variant frontotemporal dementia (bvFTD) show changes in brain structure as assessed by MRI and brain function assessed by 18FDG-PET hypometabolism. However, current understanding of the spatial and temporal interplay between these measures remains limited. METHODS: Here, we examined longitudinal atrophy and hypometabolism relationships in 15 bvFTD subjects with 2 to 4 follow-up MRI and PET scans (56 visits total). Subject-specific slopes of atrophy and hypometabolism over time were extracted across brain regions and correlated with baseline measures both locally, via Pearson correlations, and nonlocally, via sparse canonical correlation analyses (SCCA). RESULTS: Notably, we identified a robust link between initial hypometabolism and subsequent cortical atrophy rate changes in bvFTD subjects. Network-level exploration unveiled alignment between baseline hypometabolism and ensuing atrophy rates in the dorsal attention, language, and default mode networks. SCCA identified 2 significant and highly localized components depicting the connection between baseline hypometabolism and atrophy slope over time. The first centered around bilateral orbitofrontal, frontopolar, and medial prefrontal lobes, whereas the second concentrated in the left temporal lobe and precuneus. CONCLUSIONS: This study highlights 18FDG-PET as a dependable predictor of forthcoming atrophy in spatially adjacent brain regions for individuals with bvFTD.

Early mobilization of critically ill ICU patients: A survey of knowledge, perceptions, and practices of Malaysian physiotherapists.

INTRODUCTION: Early mobilization and rehabilitation of critically ill patients in the Intensive care unit (ICU) is a topic of growing interest. Current evidence suggests that early mobilization is safe, feasible, and effective at reducing the incidence of ICU-acquired weakness. However, early mobilization is still not the standard of care in most ICUs worldwide. The aim of the study was to determine the level of knowledge, perceptions, and practice among ICU physiotherapists of early mobilization in critically ill ICU patients in Malaysia. MATERIALS AND METHODS: A cross-sectional study was undertaken in 45 public, teaching, and private hospitals in Malaysia that provide ≥ 10 beds in their ICUs. Knowledge, perceived barriers, facilitators, and practice of early mobilization were assessed using a previously validated mobility survey questionnaire. RESULTS: Only 35% of ICU physiotherapists reported receiving training/courses on early mobilization in the ICU. 100 (86%) physiotherapists underestimated the incidence of ICU-acquired weakness, and 88 (75%) were unfamiliar with the current literature on early mobilization in the ICU. The need for physician orders before mobilization, medical instability, excessive sedation, and risk of dislodgement of devices or lines were the most common barriers to early mobilization. Nearly half (49 [42%]) of the respondents reported physiotherapist as early mobilization clinical champion in their setting, but the most common physiotherapy treatment techniques in the ICU reported by the respondents' were still chest physiotherapy, range of motion exercises, and bed mobility. CONCLUSION: We observed strong enthusiasm for early mobilization among Malaysian physiotherapists. Most respondents believed that early mobilization is important and beneficial to ICU patients. However, there is still a big gap in knowledge and training of early mobilization in ICU patients among Malaysian physiotherapists.

Anxious parents show higher physiological synchrony with their infants.

BACKGROUND: Interpersonal processes influence our physiological states and associated affect. Physiological arousal dysregulation, a core feature of anxiety disorders, has been identified in children of parents with elevated anxiety. However, little is understood about how parent-infant interpersonal regulatory processes differ when the dyad includes a more anxious parent. METHODS: We investigated moment-to-moment fluctuations in arousal within parent-infant dyads using miniaturised microphones and autonomic monitors. We continually recorded arousal and vocalisations in infants and parents in naturalistic home settings across day-long data segments. RESULTS: Our results indicated that physiological synchrony across the day was stronger in dyads including more rather than less anxious mothers. Across the whole recording epoch, less anxious mothers showed responsivity that was limited to 'peak' moments in their child's arousal. In contrast, more anxious mothers showed greater reactivity to small-scale fluctuations. Less anxious mothers also showed behaviours akin to 'stress buffering' - downregulating their arousal when the overall arousal level of the dyad was high. These behaviours were absent in more anxious mothers. CONCLUSION: Our findings have implications for understanding the differential processes of physiological co-regulation in partnerships where a partner is anxious, and for the use of this understanding in informing intervention strategies for dyads needing support for elevated levels of anxiety.

Endocrinological aspects of HIV infection.

PURPOSE: Patients with human immunodeficiency virus (HIV) are living longer with effective antiretroviral therapies and are enjoying near normal life span. Therefore, they are encountering endocrine issues faced by the general population along with those specific to HIV infection. The purpose of this article is to review the common endocrine aspects of HIV infection, and the early detection and management strategies for these complications. METHODS: Recent literature on HIV and endocrine disease was reviewed. RESULTS: HIV can influence endocrine glands at several levels. Endocrine glandular function may be altered by the direct effect of HIV viral proteins, through generation of systemic and local cytokines and the inflammatory response and via glandular involvement with opportunistic infections and HIV-related malignancies. Endocrine disorders seen in people with HIV include metabolic issues related to obesity such as diabetes, hyperlipidemia, lipohypertrophy, lipoatrophy and lipodystrophy and contribute significantly to quality of life, morbidity and mortality. In addition, hypogonadism, osteopenia and osteoporosis are also more prevalent in the patients with HIV. Although disorders of hypothalamic-pituitary-adrenal axis resulting in adrenal insufficiency can be life threatening, these along with thyroid dysfunction are being seen less commonly in the antiretroviral therapy (ART) era. ARTs have greatly improved life expectancy in people living with HIV but can also have adverse endocrine effects. CONCLUSIONS: Clinicians need to have a high index of suspicion for endocrine abnormalities in people with HIV as they can be potentially life threatening if untreated. Endocrine evaluation should be pursued as in the general population, with focus on prevention, early detection and treatment to improve quality of life and longevity.

Patient choice compared with no choice of intrathecal morphine dose for caesarean analgesia: a randomized clinical trial.

BACKGROUND: The study aimed to determine whether a patient's choice for their intrathecal morphine (ITM) dose reflects their opioid requirements and pain after caesarean delivery and if giving women a choice of ITM dose would reduce opioid use and improve pain scores compared with women who did not have a choice. METHODS: A total of 120 women undergoing caesarean delivery with spinal anaesthesia were enrolled in this randomized, double-blind study. Patients were randomly assigned to a choice of 100 or 200 µg ITM or no choice. The study involved deception, such that all participants were still randomly assigned 100 or 200 µg ITM regardless of choice. Rescue opioid use over the 48-h study period was the primary outcome measure. Pain at rest and movement and side effect (pruritus, nausea, and vomiting) data were collected 3, 6, 12, 24, 36 and 48 h postoperatively. Data are presented as median [95% confidence interval (CI)]. RESULTS: Women who requested the larger ITM dose required more supplemental opioid [median 0.8 (95% CI 0.4-1.3)] mg morphine equivalents at each assessment interval; P < 0.001] and reported more pain with movement [median 1.2 (95% CI 0.5-1.9)] verbal numerical rating score of 0-10 points] than patients who requested the smaller ITM dose ( P = 0.0008), regardless of the ITM dose given. There was no difference in opioid use whether the patient was offered a perceived choice or not. CONCLUSIONS: Women who were given a choice and chose the larger ITM dose correctly anticipated a greater postoperative opioid requirement and more pain compared with women who chose the smaller dose. Simply being offered a choice did not impact opioid use or pain scores after caesarean delivery. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01425762).

Does anticholinergics drug burden relate to global neuro-disability outcome measures and length of hospital stay?

PRIMARY OBJECTIVE: To assess the relationship between disability, length of stay (LOS) and anticholinergic burden (ACB) with people following acquired brain or spinal cord injury. RESEARCH DESIGN: A retrospective case note review assessed total rehabilitation unit admission. METHODS AND PROCEDURES: Assessment of 52 consecutive patients with acquired brain/spinal injury and neuropathy in an in-patient neuro-rehabilitation unit of a UK university hospital. Data analysed included: Northwick Park Dependency Score (NPDS), Rehabilitation complexity Scale (RCS), Functional Independence Measure and Functional Assessment Measure FIM-FAM (UK version 2.2), LOS and ACB. Outcome was different in RCS, NPDS and FIM-FAM between admission and discharge. MAIN OUTCOMES AND RESULTS: A positive change was reported in ACB results in a positive change in NPDS, with no significant effect on FIM-FAM, either Motor or Cognitive, or on the RCS. Change in ACB correlated to the length of hospital stay (regression correlation = -6.64; SE = 3.89). There was a significant harmful impact of increase in ACB score during hospital stay, from low to high ACB on NPDS (OR = 9.65; 95% CI = 1.36-68.64) and FIM-FAM Total scores (OR = 0.03; 95% CI = 0.002-0.35). CONCLUSIONS: There was a statistically significant correlation of ACB and neuro-disability measures and LOS amongst this patient cohort.

A systematic review of automated segmentation of 3D computed-tomography scans for volumetric body composition analysis.

Automated computed tomography (CT) scan segmentation (labelling of pixels according to tissue type) is now possible. This technique is being adapted to achieve three-dimensional (3D) segmentation of CT scans, opposed to single L3-slice alone. This systematic review evaluates feasibility and accuracy of automated segmentation of 3D CT scans for volumetric body composition (BC) analysis, as well as current limitations and pitfalls clinicians and researchers should be aware of. OVID Medline, Embase and grey literature databases up to October 2021 were searched. Original studies investigating automated skeletal muscle, visceral and subcutaneous AT segmentation from CT were included. Seven of the 92 studies met inclusion criteria. Variation existed in expertise and numbers of humans performing ground-truth segmentations used to train algorithms. There was heterogeneity in patient characteristics, pathology and CT phases that segmentation algorithms were developed upon. Reporting of anatomical CT coverage varied, with confusing terminology. Six studies covered volumetric regional slabs rather than the whole body. One study stated the use of whole-body CT, but it was not clear whether this truly meant head-to-fingertip-to-toe. Two studies used conventional computer algorithms. The latter five used deep learning (DL), an artificial intelligence technique where algorithms are similarly organized to brain neuronal pathways. Six of seven reported excellent segmentation performance (Dice similarity coefficients > 0.9 per tissue). Internal testing on unseen scans was performed for only four of seven algorithms, whilst only three were tested externally. Trained DL algorithms achieved full CT segmentation in 12 to 75 s versus 25 min for non-DL techniques. DL enables opportunistic, rapid and automated volumetric BC analysis of CT performed for clinical indications. However, most CT scans do not cover head-to-fingertip-to-toe; further research must validate using common CT regions to estimate true whole-body BC, with direct comparison to single lumbar slice. Due to successes of DL, we expect progressive numbers of algorithms to materialize in addition to the seven discussed in this paper. Researchers and clinicians in the field of BC must therefore be aware of pitfalls. High Dice similarity coefficients do not inform the degree to which BC tissues may be under- or overestimated and nor does it inform on algorithm precision. Consensus is needed to define accuracy and precision standards for ground-truth labelling. Creation of a large international, multicentre common CT dataset with BC ground-truth labels from multiple experts could be a robust solution.

Long-term treatment with raloxifene, but not bisphosphonates, reduces circulating sclerostin levels in postmenopausal women.

UNLABELLED: We determined whether suppression of sclerostin levels by estrogen treatment was mediated by anti-resorptive effect. Raloxifene, but not bisphosphonates, suppressed circulating sclerostin concentration, suggesting that sclerostin may mediate the action of estrogen on bone metabolism, independently of their anti-resorptive effects. INTRODUCTION: Circulating sclerostin concentrations are higher in postmenopausal than in premenopausal women, and estrogen treatment suppresses sclerostin levels in both men and women. We determined whether anti-resorptives may suppress the circulating sclerostin levels. METHODS: We conducted a retrospective observational study. Eighty postmenopausal women were treated with raloxifene for 19.4 ± 7.7 months (n = 16), bisphosphonates for 19.2 ± 6.7 months (n = 32), or were untreated (n = 32) for 17.1 ± 4.6 months. Plasma sclerostin concentrations were measured before and after treatment. RESULTS: Plasma sclerostin levels after treatment were significantly lower in the raloxifene than in the control group (55.8 ± 23.4 pmol/l vs. 92.1 ± 50.4 pmol/l, p = 0.046), but were similar between the bisphosphonate and control groups. Relative to baseline, raloxifene treatment markedly reduced plasma sclerostin concentration (-40.7 ± 22.8%, p < 0.001), with respect to both control (-7.5 ± 29.1%) and bisphosphonate (-3.1 ± 35.2%) groups. Changes in bone-specific alkaline phosphatase and osteocalcin levels showed reverse associations with sclerostin concentration changes in the raloxifene (γ = -0.505, p = 0.017) and control (γ = -0.410, p = 0.020) groups. CONCLUSIONS: Raloxifene, but not bisphosphonates, significantly suppressed circulating sclerostin concentration, suggesting that sclerostin may mediate the action of estrogen on bone metabolism, independently of their anti-resorptive effects.

Episiotomy: history, present and future - a review.

Childbirth has always carried traumatic stress to the woman's body. To deliver with less perineal trauma, obstetricians have used episiotomies. Episiotomy is still a common practice despite the controversy regarding its use. Weighing the risks and benefits, the scientific literature supports its selective use. With the worldwide trend to reduce the rate of episiotomy, several techniques have been proposed to achieve that. However, further research is still needed to prove their efficacy. This review will shed light on the historical background of episiotomy, its different techniques, indications, and the future of its practice.

Open versus closed treatment of unilateral subcondylar and condylar neck fractures: a prospective, randomized clinical study.

PURPOSE: The purpose of the present study was to compare closed treatment with open reduction and internal fixation for displaced unilateral subcondylar and condylar neck fractures. MATERIALS AND METHODS: A total of 32 patients with displaced unilateral condylar fractures were included in the present study. Of the 32 patients, 27 were men and 5 were women. The patients were divided into 2 groups. The group I patients were treated with closed treatment and rigid maxillomandibular fixation, and group II patients were treated with open reduction and internal fixation. The patients were assessed for maximal interincisal opening, protrusive movements, lateral excursion movements on the fractured and nonfractured sides, anatomic reduction of the condyle on radiography, pain in the temporomandibular joint, and malocclusion. Parameters such as the maximal interincisal opening, protrusive movements, and lateral excursion movements on the fractured and nonfractured sides between the 2 groups were compared statistically using an independent t test. Parameters such as anatomic reduction of the condyle, pain in the temporomandibular joint, and malocclusion between the 2 groups were compared statistically using the chi(2) test. RESULTS: No significant difference was found between the 2 groups in the maximal interincisal opening, protrusion, lateral excursion movement, malocclusion, and temporomandibular joint pain; however, a statistically significant difference was seen in the anatomic reduction of the condyle. CONCLUSIONS: The results of the present study have shown that no significant clinical difference exists between patients undergoing closed treatment and rigid maxillomandibular fixation or open reduction and internal fixation. However, a radiographically better anatomic reduction of the condylar process was seen in the patients treated with open reduction and internal fixation.

Longitudinal Analysis of Bruch Membrane Opening Morphometry in Myopic Glaucoma.

PRéCIS:: The Bruch membrane opening (BMO) was posteriorly bowed and the degree of nonplanarity increased in stable and progressive glaucoma subjects. BMO became more posterior relative to the Bruch membrane (BM) in control and both stable and progressive glaucoma subjects. PURPOSE: To investigate longitudinal changes in morphologic characteristics of the BMO in control and glaucomatous subjects. MATERIALS AND METHODS: A total of 53 myopic eyes (17 control, 6 suspect, 20 stable glaucoma, and 10 progressing glaucoma) were followed for an average of 4.2±1.4 years and imaged at the baseline and 2 follow-up appointments using a 1060 nm swept-source optical coherence tomography system. BM and BMO were segmented, and 4 morphometric BMO parameters (area, ellipse ratio, nonplanarity, and depth) were measured. RESULTS: There were no significant changes in BMO area or ellipse ratio for all groups. BMO nonplanarity was shown to increase in the glaucoma groups. BMO depth relative to BM increased in all groups except the suspects (control: 8.1 µm/y, P=0.0001; stable glaucoma: 3.5 µm/y, P=0.0001; progressing glaucoma: 14.0 µm/y, P=0.0026). In linear mixed-model analysis, axial length was positively associated with BMO area in all groups except for progressing glaucoma, and with BMO nonplanarity in stable glaucoma. It was not a significant factor to the slopes of the BMO parameters in the ANCOVA analysis of slopes. CONCLUSIONS: Longitudinally, BMO increased in nonplanarity in the glaucoma eyes, and its axial position relative to BM became more posterior in both control and glaucoma eyes.

Study the Longitudinal in vivo and Cross-Sectional ex vivo Brain Volume Difference for Disease Progression and Treatment Effect on Mouse Model of Tauopathy Using Automated MRI Structural Parcellation.

Brain volume measurements extracted from structural MRI data sets are a widely accepted neuroimaging biomarker to study mouse models of neurodegeneration. Whether to acquire and analyze data in vivo or ex vivo is a crucial decision during the phase of experimental designs, as well as data analysis. In this work, we extracted the brain structures for both longitudinal in vivo and single-time-point ex vivo MRI acquired from the same animals using accurate automatic multi-atlas structural parcellation, and compared the corresponding statistical and classification analysis. We found that most gray matter structures volumes decrease from in vivo to ex vivo, while most white matter structures volume increase. The level of structural volume change also varies between different genetic strains and treatment. In addition, we showed superior statistical and classification power of ex vivo data compared to the in vivo data, even after resampled to the same level of resolution. We further demonstrated that the classification power of the in vivo data can be improved by incorporating longitudinal information, which is not possible for ex vivo data. In conclusion, this paper demonstrates the tissue-specific changes, as well as the difference in statistical and classification power, between the volumetric analysis based on the in vivo and ex vivo structural MRI data. Our results emphasize the importance of longitudinal analysis for in vivo data analysis.

Evidence of structural remodeling in the dyssynchronous failing heart.

Ventricular remodeling of both geometry and fiber structure is a prominent feature of several cardiac pathologies. Advances in MRI and analytical methods now make it possible to measure changes of cardiac geometry, fiber, and sheet orientation at high spatial resolution. In this report, we use diffusion tensor imaging to measure the geometry, fiber, and sheet architecture of eight normal and five dyssynchronous failing canine hearts, which were explanted and fixed in an unloaded state. We apply novel computational methods to identify statistically significant changes of cardiac anatomic structure in the failing and control heart populations. The results demonstrate significant regional differences in geometric remodeling in the dyssynchronous failing heart versus control. Ventricular chamber dilatation and reduction in wall thickness in septal and some posterior and anterior regions are observed. Primary fiber orientation showed no significant change. However, this result coupled with the local wall thinning in the septum implies an altered transmural fiber gradient. Further, we observe that orientation of laminar sheets become more vertical in the early-activated septum, with no significant change of sheet orientation in the late-activated lateral wall. Measured changes in both fiber gradient and sheet structure will affect both the heterogeneity of passive myocardial properties as well as electrical activation of the ventricles.

Comparison of motor diagnoses by Chicago Classification versions 2.0 and 3.0 on esophageal high-resolution manometry.

BACKGROUND: The Chicago Classification (CC) uses high-resolution manometry (HRM) software tools to designate esophageal motor diagnoses. We evaluated changes in diagnostic designations between two CC versions, and determined motor patterns not identified by either version. METHODS: In this observational cohort study of consecutive patients undergoing esophageal HRM over a 6-year period, proportions meeting CC 2.0 and 3.0 criteria were segregated into esophageal outflow obstruction, hypermotility, and hypomotility disorders. Contraction wave abnormalities (CWA), and 'normal' cohorts were recorded. Symptom burden was characterized using dominant symptom intensity and global symptom severity. Motor diagnoses, presenting symptoms, and symptom burden were compared between CC 2.0 and 3.0, and in cohorts not meeting CC diagnoses. KEY RESULTS: Of 2569 eligible studies, 49.9% met CC 2.0 criteria, but only 40.3% met CC 3.0 criteria (P<.0001). Between CC 2.0 and 3.0, 82.8% of diagnoses were concordant. Discordance resulted from decreasing proportions of hypermotility (4.4%) and hypomotility (9.0%) disorders, and increase in 'normal' designations (13.0%); esophageal outflow obstruction showed the least variation between CC versions. Symptom burden was higher with CC 3.0 diagnoses (P≤.005) but not with CC 2.0 diagnoses (P≥.1). Within 'normal' cohorts for both CC versions, CWA were associated with higher likelihood of esophageal symptoms, especially dysphagia, regurgitation, and heartburn, compared to truly normal studies (P≤.02 for each comparison). CONCLUSIONS AND INFERENCES: Despite lower sensitivity, CC 3.0 identifies esophageal motor disorders with higher symptom burden compared to CC 2.0. CWA, which are associated with both transit and perceptive symptoms, are not well identified by either version.

Placenta accreta: Elective versus emergent delivery as a major predictor of blood loss.

OBJECTIVE: To compare blood loss and the use for blood transfusion between elective (planned) and emergent cesarean hysterectomy performed for placenta accreta by a single, multidisciplinary team and to present the team's pre-operative evaluation and the surgical technique. STUDY DESIGN: Prospective cohort study at a single tertiary care center. Maternal and neonatal outcomes were compared between elective and emergent delivery of pregnancies complicated by placenta accreta. The primary outcomes were the need for blood transfusion and the number of units transfused. RESULTS: A total of 28 cases of confirmed placenta accreta underwent peripartum hysterectomy, including 22 as elective and 6 as emergent. Eleven out of 22 (50%) subjects in the elective group received blood transfusion, while all subjects in the emergency group required transfusion (p = 0.03). More importantly, the number of units of packed red blood cells transfused was only 1.90 (±2.20) units in the elective cases compared to 7.83 (±4.90) units in cases performed emergently (p = 0.03). CONCLUSION: Elective cesarean hysterectomy for this indication using a clearly outlined surgical approach is associated with significantly lower blood loss and hence less need for transfusion, compared to its emergent counterpart.

Anterior Segment Optical Coherence Tomography for Targeted Transconjunctival Suture Placement in Overfiltering Trabeculectomy Blebs.

PURPOSE: To demonstrate the utility of swept-source anterior segment optical coherence tomography (SS-AS-OCT) in guiding placement of transconjunctival sutures in hypotonous patients after a trabeculectomy. PATIENTS AND METHODS: This is a longitudinal case series of 10 eyes from 10 patients who required transconjunctival sutures after a trabeculectomy. SS-AS-OCT was used to aid in the placement of the sutures to improve the function of the overfiltering bleb. RESULTS: SS-AS-OCT reliably identified localized areas of overfiltering, allowing for targeted suture placement in 8 eyes. The 2 eyes in which localized areas of overfiltering were not found required further surgical intervention. CONCLUSIONS: SS-AS-OCT enhances transconjunctival suturing for overfiltering blebs when focal fluid accumulation is visualized.

Antenatal corticosteroids in the late preterm period: A prospective cohort study.

OBJECTIVE: The study objective was to examine the effect of antenatal corticosteroids on the incidence of short-term neonatal morbidities in singletons born during the late preterm period. STUDY DESIGN: This was a prospective cohort study of singleton gestations at risk of imminent delivery between 34 0/7 and 36 6/7 weeks. Short-term neonatal morbidities were compared between the corticosteroid exposed and non-exposed groups. The rates of Neonatal Morbidity Composite and Any Adverse Neonatal Morbidity were then compared between the two groups. RESULTS: During the two-year study period, a total of 295 subjects were included. Of those, 74 were exposed to antenatal corticosteroids, while 221 cases constituted the non-exposed group. There was no statistically significant difference in the rate of Any Adverse Neonatal Morbidity (47.3% vs. 40.7% , p = 0.32) or the rate of Neonatal Morbidity Composite (34.4% vs. 37.8% , p = 0.59) between the two groups. Additionally, there was no statistically significant difference in the rates of neonatal intensive care unit admission, respiratory distress syndrome, transient tachypnea of the newborn, hypothermia, and need for phototherapy. CONCLUSION: Administration of antenatal corticosteroids to parturients at risk of imminent delivery during the late preterm period does not appear to reduce short-term neonatal morbidities.