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Nevin Manimala Statistics

MRXCAT2.0: Synthesis of realistic numerical phantoms by combining left-ventricular shape learning, biophysical simulations and tissue texture generation

J Cardiovasc Magn Reson. 2023 Apr 20;25(1):25. doi: 10.1186/s12968-023-00934-z.

ABSTRACT

BACKGROUND: Standardised performance assessment of image acquisition, reconstruction and processing methods is limited by the absence of images paired with ground truth reference values. To this end, we propose MRXCAT2.0 to generate synthetic data, covering healthy and pathological function, using a biophysical model. We exemplify the approach by generating cardiovascular magnetic resonance (CMR) images of healthy, infarcted, dilated and hypertrophic left-ventricular (LV) function.

METHOD: In MRXCAT2.0, the XCAT torso phantom is coupled with a statistical shape model, describing population (patho)physiological variability, and a biophysical model, providing known and detailed functional ground truth of LV morphology and function. CMR balanced steady-state free precession images are generated using MRXCAT2.0 while realistic image appearance is ensured by assigning texturized tissue properties to the phantom labels.

FINDING: Paired CMR image and ground truth data of LV function were generated with a range of LV masses (85-140 g), ejection fractions (34-51%) and peak radial and circumferential strains (0.45 to 0.95 and – 0.18 to – 0.13, respectively). These ranges cover healthy and pathological cases, including infarction, dilated and hypertrophic cardiomyopathy. The generation of the anatomy takes a few seconds and it improves on current state-of-the-art models where the pathological representation is not explicitly addressed. For the full simulation framework, the biophysical models require approximately two hours, while image generation requires a few minutes per slice.

CONCLUSION: MRXCAT2.0 offers synthesis of realistic images embedding population-based anatomical and functional variability and associated ground truth parameters to facilitate a standardized assessment of CMR acquisition, reconstruction and processing methods.

PMID:37076840 | DOI:10.1186/s12968-023-00934-z

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Predictors of thyroid adverse events during cancer immunotherapy: a real-life experience at a single center

J Endocrinol Invest. 2023 Apr 20. doi: 10.1007/s40618-023-02096-2. Online ahead of print.

ABSTRACT

BACKGROUND: Thyroid dysfunction is among the most common immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) therapy. Data regarding potential predictors of the development of thyroid irAEs are still limited and sometimes conflicting.

PATIENTS AND METHODS: We assessed potential risk factors and clinical outcomes associated with the onset of thyroid irAEs in a cohort of patients with different types of cancer treated with ICIs at a single center. Clinical and biochemical data, including thyroid function tests and autoantibodies at baseline and during treatment, were collected, and the onset of thyroid irAEs was recorded. Patients with thyroid dysfunction and/or under levothyroxine therapy before starting ICI were excluded.

RESULTS: 110 patients (80 M, 30 F, aged 32-85 years; 56.4% non-small-cell lung cancer, 87% treated with anti-PD-1) with complete information were included in the study. Among them, 32 (29%) developed thyroid irAEs during ICIs therapy. Primary hypothyroidism was the most common irAEs, occurring in 31 patients (28.18% of the whole cohort), including 14 patients who experienced a transient thyrotoxicosis. About 60% of irAEs occurred within the first 8 weeks of therapy. At multivariate analysis, anti-thyroid autoantibodies positivity at baseline (OR 18.471, p = 0.022), a pre-existing (autoimmune and non-autoimmune) thyroid disorder (OR 16.307, p < 0.001), and a family history of thyroid diseases (OR = 9.287, p = 0.002) were independent predictors of the development of thyroid irAEs.

CONCLUSION: Our data confirm the high frequency of thyroid dysfunctions (mostly hypothyroidism) during ICIs, and provide data on valuable predictors of thyroid toxicities that may help clinicians in identifying patients at risk for developing irAEs.

PMID:37076759 | DOI:10.1007/s40618-023-02096-2

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Effects of intravascular photobiomodulation on cognitive impairment and crossed cerebellar diaschisis in patients with traumatic brain injury: a longitudinal study

Lasers Med Sci. 2023 Apr 20;38(1):108. doi: 10.1007/s10103-023-03764-8.

ABSTRACT

The association between intravascular photobiomodulation (iPBM) and crossed cerebellar diaschisis (CCD) and cognitive dysfunction in patients with traumatic brain injury (TBI) remains unknown. We postulate that iPBM might enable greater neurologic improvements. The objective of this study was to evaluate the clinical impact of iPBM on the prognosis of patients with TBI. In this longitudinal study, patients who were diagnosed with TBI were recruited. CCD was identified from brain perfusion images when the uptake difference of both cerebella was > 20%. Thus, two groups were identified: CCD( +) and CCD( -). All patients received general traditional physical therapy and three courses of iPBM (helium-neon laser illuminator, 632.8 nm). Treatment assemblies were conducted on weekdays for 2 consecutive weeks as a solitary treatment course. Three courses of iPBM were performed over 2-3 months, with 1-3 weeks of rest between each course. The outcomes were measured using the Rancho Los Amigos Levels of Cognitive Functioning (LCF) tool. The chi-square test was used to compare categorical variables. Generalized estimating equations were used to verify the associations of various effects between the two groups. p < 0.05 indicated a statistically significant difference. Thirty patients were included and classified into the CCD( +) and CCD( -) groups (n = 15, each group). Statistics showed that before iPBM, CCD in the CCD( +) group was 2.74 (exp 1.0081) times higher than that of CCD( -) group (p = 0.1632). After iPBM, the CCD was 0.64 (exp-0.4436) times lower in the CCD( +) group than in the CCD( -) group (p < 0.0001). Cognitive assessment revealed that, before iPBM, the CCD( +) group had a non-significantly 0.1030 lower LCF score than that of CCD( -) group (p = 0.1632). Similarly, the CCD( +) group had a non-significantly 0.0013 higher score than that of CCD( -) after iPBM treatment (p = 0.7041), indicating no significant differences between the CCD( +) or CCD( -) following iPBM and general physical therapy. CCD was less likely to appear in iPBM-treated patients. Additionally, iPBM was not associated with LCF score. Administration of iPBM could be applied in TBI patients to reduce the occurrence of CCD. The study failed to show differences in cognitive function after iPBM, which still serves as an alternative non-pharmacological intervention.

PMID:37076743 | DOI:10.1007/s10103-023-03764-8

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Importance of etiology in canalicular obstruction surgery

Int Ophthalmol. 2023 Apr 20. doi: 10.1007/s10792-023-02719-w. Online ahead of print.

ABSTRACT

PURPOSE: The treatment options for canalicular obstruction remain controversial, and there are different approaches. In this study, we aimed to evaluate the success of balloon dilatation and silicon tube intubation according to the etiology in patients with canalicular obstruction.

METHODS: The files of 91 patients with isolated monocanalicular obstruction were retrospectively reviewed. Patients were grouped according to surgical methods (Group A: both balloon dilatation and silicon tube intubation; Group B: Only balloon dilatation) and etiologies (topical anti-glaucomatous usage-related, inflammatory, chemotherapy-related, radiotherapy-related, trauma-related, idiopathic). Preoperative and postoperative Munk scores and lacrimal irrigation results were noted in all cases.

RESULTS: Munk score was found to be statistically significantly lower in the 1st year in both groups. The patency rate with lacrimal syringing was found to be statistically significantly higher in group A. Success rates both in the munk score and lacrimal passage patency were found to be statistically significantly lower in inflammatory etiology than other etiologies.

CONCLUSIONS: Both techniques can be used as first-line therapies for canalicular obstruction. It should be considered that recurrence may develop in stenosis of inflammatory origin and more invasive surgery may be required.

PMID:37076655 | DOI:10.1007/s10792-023-02719-w

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Nevin Manimala Statistics

Vasoconstriction during non-hypotensive hypovolemia is not associated with activation of baroreflex: A causality-based approach

Pflugers Arch. 2023 Apr 20. doi: 10.1007/s00424-023-02811-1. Online ahead of print.

ABSTRACT

Non-hypotensive hypovolemia simulated with oscillatory lower body negative pressure in the range of -10 to -20 mmHg is associated with vasoconstriction {increase in total peripheral vascular resistance (TPVR)}. Due to the mechanical stiffening of vessels, there is a disjuncture of mechano-neural coupling at the level of arterial baroreceptors which has not been investigated. The study was designed to quantify both the cardiac and vascular arms of the baroreflex using an approach based on Wiener-Granger causality (WGC) – partial directed coherence (PDC). Thirty-three healthy human volunteers were recruited and continuous heart rate and blood pressure {systolic (SBP), diastolic (DBP), and mean (MBP)} were recorded. The measurements were taken in resting state, at -10 mmHg (level 1) and -15 mmHg (level 2). Spectral causality – PDC was estimated from the MVAR model in the low-frequency band using the GMAC MatLab toolbox. PDC from SBP and MBP to RR interval and TPVR was calculated. The PDC from MBP to RR interval showed no significant change at -10 mmHg and -15 mmHg. No significant change in PDC from MBP to TPVR at -10 mmHg and -15 mmHg was observed. Similar results were obtained for PDC estimation using SBP as input. However, a significant increase in TPVR from baseline at both levels of oscillatory LBNP (p-value <0.001). No statistically significant change in PDC from blood pressure to RR interval and blood pressure to TPVR implies that vasoconstriction is not associated with activation of the arterial baroreflex in ≤-15 mmHg LBNP. Thereby, indicating the role of cardiopulmonary reflexes during the low level of LBNP simulated non-hypotensive hypovolemia.

PMID:37076560 | DOI:10.1007/s00424-023-02811-1

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Effectiveness of Pharmacopuncture Therapy in Adhesive Capsulitis: a Study Protocol for a Pragmatic Randomized Controlled Trial

J Acupunct Meridian Stud. 2023 Apr 30;16(2):70-78. doi: 10.51507/j.jams.2023.16.2.70.

ABSTRACT

BACKGROUND: Adhesive capsulitis is a progressive, idiopathic disorder that significantly impacts individuals̓ daily lives and increases their medical burden. Pharmacopuncture therapy, which combines acupuncture techniques with herbal medicine, involves injecting herbal extracts into specific acupoints. This study aims to determine the effectiveness and safety of pharmacopuncture therapy in comparison to physiotherapy (PT) for treating adhesive capsulitis.

METHODS: This research protocol outlines a two-arm, parallel, multi-center, pragmatic randomized controlled trial. Fifty participants will be randomly allocated to either the pharmacopuncture therapy or PT group, and they will receive 12 sessions of their respective therapies over a 6-week period. The primary outcome measure is the numeric rating scale for shoulder pain. Secondary outcomes include the visual analog scale score for shoulder pain, Shoulder Pain and Disability Index, Patients̓ Global Impression of Change score, Short Form-12 Health Survey Version 2 score, and EuroQol-5 Dimension. Statistical analysis will be conducted based on the intention-to-treat principle.

DISCUSSION: This trial may offer high-quality and reliable clinical evidence for evaluating the effectiveness and safety of pharmacopuncture therapy compared to PT in the treatment of adhesive capsulitis. Furthermore, this study will serve as a valuable guideline for practitioners when making clinical decisions and managing adhesive capsulitis.

PMID:37076182 | DOI:10.51507/j.jams.2023.16.2.70

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Abdominal Acupuncture for Non-Responding TMD Patients: a Retrospective Observational Study in General Practice

J Acupunct Meridian Stud. 2023 Apr 30;16(2):56-64. doi: 10.51507/j.jams.2023.16.2.56.

ABSTRACT

BACKGROUND: Pain related to Temporomandibular Disorders (TMD) is severe, negatively affecting patients’ quality of life, and often resistant to conventional treatments. Abdominal Acupuncture (AA) is known to be particularly effective for pain, especially chronic and musculoskeletal pain, but it is still poorly studied and never investigated in TMD patients.

OBJECTIVES: To analyze the efficacy of AA for the treatment of patients with subacute and chronic pain related to TMD and non-responding to previous conventional therapies (occlusal splint, medications, physical therapy).

METHODS: Twenty-eight patients, 24 F and four M (mean age 49.36 years), were recruited from January 2019-February 2021. All patients underwent AA treatment: two sessions per week for four weeks, for a total of eight sessions. At the beginning of therapy (T0) and at the end of the cycle (T1) the following data were evaluated: maximum mouth opening (MMO); cranio-facial pain related to TMD (verbal numeric scale, VNS); pain interference with normal activities and quality of life of patients (Brief Pain Inventory, BPI); oral functioning (Oral Behavior Checklist, OBC); impression of treatment effectiveness (Patients’ Global Impression of Improvement, PGI-I Scale). Statistical comparison of data before and after the AA treatment was performed by Wilcoxon’s signed-rank test (significance level p < 0.05).

RESULTS: The MMO values were significantly improved after one cycle of AA (p = 0.0002). In addition, TMD-related pain had a statistically significant decline following AA treatment (all p < 0.001). Patients’ general activity and quality of life (BPI) were described as improved following a course of AA, with statistically significant values for all aspects considered (all p < 0.05).

CONCLUSION: Abdominal acupuncture resulted in effective treatment of subacute/chronic-resistant pain related to TMD, capable of improving mandibular function and facial pain, and reduced the interference of pain affecting patients’ quality of life.

PMID:37076180 | DOI:10.51507/j.jams.2023.16.2.56

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Biomechanical Assessment of a Novel Sharp-Tipped Screw for 1-Step Minimally Invasive Pedicle Screw Placement Under Navigation

Int J Spine Surg. 2023 Apr 19:8470. doi: 10.14444/8470. Online ahead of print.

ABSTRACT

BACKGROUND: The objective of this study was to assess the pullout force of a novel sharp-tipped screw developed for single-step, minimally invasive pedicle screw placement guided by neuronavigation compared with the pullout force for traditional screws.

METHODS: A total of 60 human cadaveric lumbar pedicles were studied. Three different screw insertion techniques were compared: (A) Jamshidi needle and Kirschner wire without tapping; (B) Jamshidi needle and Kirschner wire with tapping; and (C) sharp-tipped screw insertion. Pullout tests were performed at a displacement rate of 10 mm/min recorded at 20 Hz. Mean values of these parameters were compared using paired t tests (left vs right in the same specimen): A vs B, A vs C, and B vs C. Additionally, 3 L1-L5 spine models were used for timing each screw insertion technique for a total of 10 screw insertions for each technique. Insertion times were compared using 1-way analysis of variance.

RESULTS: The mean pullout force for insertion technique A was 1462.3 (597.5) N; for technique B, it was 1693.5 (805.0) N; and for technique C, it was 1319.0 (735.7) N. There was no statistically significant difference in pullout force between techniques (P > 0.08). The average insertion time for condition C was significantly less than that for conditions A and B (P < 0.001).

CONCLUSIONS: The pullout force of the novel sharp-tipped screw placement technique is equivalent to that of traditional techniques. The sharp-tipped screw placement technique appears biomechanically viable and has the advantage of saving time during insertion.

CLINICAL RELEVANCE: Single-step screw placement using high resolution 3-dimensional navigation has the potential to streamline workflow and reduce operative time.

PMID:37076254 | DOI:10.14444/8470

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Free academic discourse and the law: the case of liposomal bupivacaine

Reg Anesth Pain Med. 2023 Apr 19:rapm-2023-104547. doi: 10.1136/rapm-2023-104547. Online ahead of print.

ABSTRACT

Liposomal bupivacaine has been the topic of intense academic debate over the past years culminating in an industry-initiated libel lawsuit against the American Society of Anesthesiologists and various other defendants. In this Daring Discourse, we first aim to provide a general overview of main themes in the ongoing controversy: (1) between-study heterogeneity, (2) the high number of negative high-quality reviews and meta-analyses, (3) publication bias in the context of an active role of industry and (4) difference between statistical and clinical significance. We then discuss the contents of the lawsuit, its potential implications and what the recent resolution of this lawsuit means for the future of research and the academic discourse on liposomal bupivacaine.

PMID:37076253 | DOI:10.1136/rapm-2023-104547

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A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a bupivacaine hydrochloride implant in patients undergoing abdominoplasty

Reg Anesth Pain Med. 2023 Apr 19:rapm-2022-104110. doi: 10.1136/rapm-2022-104110. Online ahead of print.

ABSTRACT

INTRODUCTION: Surgical site infiltration with bupivacaine hydrochloride (HCl) is a standard element of postoperative analgesia for soft tissue surgeries, but results in short-lived analgesia. A novel bupivacaine implant, XARACOLL (bupivacaine HCl), is Food and Drug Administration approved for treatment of acute postsurgical pain following adult inguinal herniorrhaphy. This study examined the efficacy and safety of the bupivacaine implant (300 mg) compared with placebo for postsurgical pain after abdominoplasty.

METHODS: In this double-blind, placebo-controlled study, patients undergoing abdominoplasty were randomized to three 100 mg bupivacaine implants or three placebo collagen implants, in a 1:1 ratio, implanted intraoperatively. No other analgesics were administered into the surgical site. Patients were allowed opioids and acetaminophen for postoperative pain. Patients were followed for up to 30 days after treatment.

PRIMARY OUTCOME: the analgesic effect of the bupivacaine implants through 24 hours postsurgery, measured by the sum of time-weighted pain intensity (SPI24). Prespecified key secondary outcomes included SPI48 and SPI72, percentage of opioid-free patients through 24, 48, and 72 hours, and adverse events, which were tested sequentially to control for multiplicity (ie, if the first variable failed to reach significance, no subsequent variables were declared statistically significant).

RESULTS: The bupivacaine implant patients (n=181) reported statistically significant lower SPI24 (mean (SD) SPI24=102 (43), 95% CI 95 to 109) compared with placebo patients (n=184; SPI24=117 (45), 95% CI 111 to 123, p=0.002). SPI48 was 190 (88, 95% CI 177 to 204) for INL-001 and 206 (96, 95% CI 192 to 219) for placebo, and not significantly different between groups. The subsequent secondary variables were therefore declared not statistically significant. SPI72 was 265 (131, 95% CI 244 to 285) for INL-001 and 281 (146, 95% CI 261 to 301) for placebo. The opioid-free percentage of patients at 24, 48, and 72 hours was 19%, 17%, and 17% for INL-001 and 6.5% for placebo patients (at all timepoints). The only adverse event occurring in ≥5% of patients and for which proportion INL-001 >placebo was back pain (7.7% vs 7.6%).

CONCLUSION: The study design was limited by not containing an active comparator. Compared with placebo, INL-001 provides postoperative analgesia that is temporally aligned with the period of maximal postsurgical pain in abdominoplasty and offers a favorable safety profile.

TRIAL REGISTRATION NUMBER: NCT04785625.

PMID:37076252 | DOI:10.1136/rapm-2022-104110