Anatomical Compartments Research Articles

Fasciotomy done for vascular trauma at a tertiary care centre in Sri Lanka

Introduction Compartment syndrome is a major factor contributing to limb loss and poor outcome following lower limb vascular injuries. Method This is a retrospective study done on patients with vascular injuries and undergone fasciotomy at the accident service operation theatre (ASOT) at the national hospital of Sri Lanka (NHSL), during a period of one year. Cases with Incomplete documentation were excluded. Data on patient demographics, time of injury, and time of fasciotomy, associated fractures, muscle viability and outcome were collected. Results A total of 30 cases were included. 26 (86%) were males. Nine (30%) were upper limb and 21(70%) were lower limb fasciotomy. The cause for limb injuries were road traffic accidents (RTA) in 18 (58.1%), trap gun injury in five (16.1%). All the fasciotomy were done prior to revascularization. 19 (63.3%) had fractures (12 (63%) were open and seven (36%) closed). six (20%) fasciotomy were done for compartment syndrome, 24 (80%) were done prophylactically. Three patients with compartment syndrome had open fractures (50%) and three had closed fractures (50%). On fasciotomy, in four cases all four leg compartment muscles were non-viable, two had non-viable three compartments and one patient had non-viable two compartments. The mean delay in patients who had all compartments viable was 3.7 hours (2-6.5) and the mean delay in patients with three or four non-viable compartments was 12.2hours (7-24). This difference was statistically significant (p-0.0001). The fasciotomy delay was also significant (p-0.0001) between the patients who had an amputation and limb salvage. Overall amputation rate was 20% in this series. Mean time of delay from admission to NHSL to the time of fasciotomy was 1.8 hours (1-3.5). Mean time of injury to time of fasciotomy was 5.42 hours (2-24). Discussion Number of non-viable compartments is significantly associated with the duration between time of injury to time of fasciotomy(P-0.0001). Therefore we suggest early fasciotomy before transfer

Rectal perforation secondary to invasive cervical cancer presenting as perineal necrotizing fasciitis with subsequent hindquarter amputation: a case report

Necrotizing fasciitis (NF) is a life-threatening soft tissue infection rarely associated with gynecological malignancies. We present a unique case of NF arising from a locally advanced cervical cancer eroding into the rectum, causing occult fecal spillage leading to severe infection and necessitating a hindquarter amputation. A 39-year-old woman presented with sepsis and a necrotic gluteal wound. Extensive debridement revealed "dishwater"-like discharge throughout the left leg fascial compartments, necessitating hindquarter amputation. Despite initial suspicion of a primary skin infection, further investigation revealed a posterolateral rectal perforation secondary to advanced cervical cancer, confirmed by biopsy and imaging. Microbiology identified Streptococcus constellatus, intermedius, and anginosus. This case highlights the atypical presentation of NF associated with advanced cervical cancer. High clinical suspicion and early surgical intervention are crucial for survival. This case expands the understanding of NF etiology and emphasizes the importance of considering rare causes, even in the absence of traditional risk factors.

Updated automated PROMISE assessment: Treatment response evaluation based on PSMA PET/CT.

48 Background: PSMA PETs can track treatment response in patients with prostate cancer. Recent integration of the RECIP framework with PROMISE v2 allows quantitative assessment of PSMA PETs. While useful for assessing differentially responding lesions, manual measurement and tracking is cumbersome and PSA reliance can be misleading. We evaluated an automated AI-enabled platform, aPROMISE, for longitudinal lesion tracking to evaluate treatment response based solely upon tumor volume. Methods: Patients with castration sensitive or resistant disease undergoing 18F-DCFPyL PET/CTs during workup and at ≥3 months after treatment were included. Tracer-avid lesions were identified using the aPROMISE algorithm. Detected lesions were manually approved by an experienced nuclear medicine physician. After lesion identification and approval, the total tumor volume was calculated. The corresponding low-dose CT was auto-segmented, allowing anatomic compartment (prostate/bed, node, bone, or visceral) annotation of 18F-DCFPyL-avid lesions. Baseline and follow-up PETs were deformably co-registered to automatically match individual lesions if they were in the same anatomic compartment, and had overlap <10 mm center-to-center (<50 mm for rib lesions). Unmatched lesions on follow-up PET were noted as new. Response was assessed as CR (no avidity in follow-up), PR (volume decrease ≥30% without new lesions), SD (volume decrease ≥30% with new lesions), or PD (volume increase ≥20% plus new lesions). Volume changes at the total tumor and individual lesion levels were also assessed independent of RECIP imaging criteria. Results: The automated algorithm assigned the correct RECIP classification in 97% of the 67 cases with 14 as CR, 14 as PR, 20 as SD, and 19 as PD. 1027 of the 1686 lesions identified on baseline PET were seen on follow-up. 673 of the 1700 lesions identified on follow-up PET were new. Conclusions: For response assessment using 18F-DCFPyL PET/CT and RECIP imaging criteria, the automated algorithm and manual detection achieved the same clinical classifications. Automated approaches may allow more granular lesion analysis The precision and accuracy this automated process is being validated in prospective clinical studies.

A Comprehensive Analysis on Compartment Syndrome of the Thigh Okoro Ogheneyebrorue Godswill and Isioma Cynthia Nwaokoro

The surgical emergency known as compartment syndrome of the thighs carries a high risk of mortality as well as morbidity. The purpose of this review was to evaluate the degree of effect regarding compartment syndrome of the thighs. This evaluation included a thorough literature review in order to accomplish the study's objective. Also, relevant literatures were adopted and specific search terms including " thigh” and syndrome” utilized while data achieved from EBSCO and Google Scholar libraries. According to some writers, to be able to reduce the possibility of recurring ischemic alterations, all muscle compartments of the implicated limb must be released during the fasciotomy. To be able to prevent fibrosis and contracture, which impair transfers and lower extremity dressing abilities in patients with concurrent spinal cord injury, surgical decompression is necessary. There is currently a dearth of information on the causes, effectiveness of one versus two fasciotomies, types of wound closure, and complication rates of compartment syndrome of the thighs.

Examining the Forearm Intersection through Palpation and Ultrasonography.

Forearm intersection syndrome causes pain, swelling, and a rub at the dorsal distal forearm where the first extensor compartment muscles intersect with the second compartment tendons. Although primary care settings tend to treat mild cases, high-performance athletes may suffer from severe symptoms that require surgery. This proof-of-concept study aims to help detect the anatomical substrate of forearm intersection syndrome using palpation and ultrasonography when available. Five individuals were studied using independent palpation and ultrasonography to identify the first dorsal compartment muscles and the second dorsal compartment tendons. The distances between the dorsal (Lister's) tubercle of the radius and the ulnar and radial edges of the first dorsal compartment muscles were measured to determine the location and extent of the muscle-tendon intersection. The palpatory and ultrasonographic measurements were compared using descriptive statistics and the paired t-test. The mean distances from the dorsal tubercle of the radius to the ulnar and radial borders of the first dorsal compartment muscles were 4.0 cm (SE 0.42) and 7.7 cm (SE 0.56), respectively, based on palpation. By ultrasonography, the corresponding distances were 3.5 cm (SD 1.05, SE 0.47) and 7.0 cm (SD 1.41, SE 0.63). Both methods showed a similar overlap length. However, ultrasonography revealed a shorter distance between the dorsal tubercle of the radius and the ulnar border of the first compartment than palpation (p = 0.0249). Our findings indicate that a basic knowledge of anatomy should help health professionals diagnose forearm intersection syndrome through palpation and, if available, ultrasonography.

A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis.

Chronic inflammation and insulin resistance are highly prevalent in patients on maintenance haemodialysis (MHD) and are strongly associated with protein energy wasting. We conducted a pilot, randomized, placebo-controlled trial of recombinant human interleukin-1 receptor antagonist (IL-1ra) and pioglitazone to explore the safety, feasibility and efficacy for insulin-mediated protein metabolism in patients undergoing MHD. Twenty-four patients were randomized to receive IL-1ra, pioglitazone or placebo for 12weeks. Changes in serum inflammatory markers and insulin-mediated protein synthesis, breakdown and net balance in the whole-body and skeletal muscle compartments were assessed using hyperinsulinaemic-hyperaminoacidemic clamp technique at baseline and Week 12. Among 24 patients, median (interquartile range) age was 51 (40, 61), 79% were African American and 21% had diabetes mellitus. All patients initiated on intervention completed the study, and no serious adverse events were observed. There was a statistically significant decrease in serum high-sensitivity C-reactive protein in the pioglitazone group compared with placebo, but not in the IL-1ra group. No significant differences in the changes of whole-body or skeletal muscle protein synthesis, breakdown and net balance were found between the groups. In this pilot study, there were no statistically significant effects of 12weeks of IL-1ra or pioglitazone on protein metabolism in patients on MHD. gov registration: NCT02278562.

Biocompatible metal-organic frameworks as promising platforms to eradicate HIV reservoirs ex vivo in people living with HIV.

The HIV attacks the immune system provoking an infection that is considered a global health challenge. Despite antiretroviral treatments being effective in reducing the plasma viral load in the blood to undetectable levels in people living with HIV (PLWH), the disease is not cured and has become chronic. This happens because of the existence of anatomical and cellular viral reservoirs, mainly located in the lymph nodes and gastrointestinal tract, which are composed of infected CD4+ T cells with a resting memory phenotype and inaccessible to antiretroviral therapy. Herein, a new therapeutic strategy based on nanotechnology is presented. Different combinations of antiretroviral drugs (bictegravir/tenofovir/emtricitabine and nevirapine/tenofovir/emtricitabine) and toll-like receptor agonists were encapsulated into metal-organic frameworks (MOFs) PCN-224 and ZIF-8. The encapsulation efficiencies of all the drugs, as well as their release rate from the carriers, were measured. In vitro studies about the cell viability, the hemocompatibility, and the platelet aggregation of the MOFs were carried out. Epifluorescence microscopy assays confirmed the ability of ZIF-8 to target a carboxyfluorescein probe inside HeLa cell lines and PBMCs. These results pave the way for the use of these structures to eliminate latent HIV reservoirs from anatomical compartments through the activation of innate immune cells, and a higher efficacy of the triplet combinations of antiretroviral drugs.

Design and Test of an Intraoral Electrode Grid for Tongue High-Density Electromyography.

Tongue motor function is crucial in a wide range of basic activities and its impairment affects quality of life. The electrophysiological assessment of the tongue relies primarily on needle electromyography, which is limited by its invasiveness and inability to capture the concurrent activity of the different tongue muscles. This work aimed at developing an intraoral grid for high-density surface electromyography (HDsEMG) to non-invasively map the electrical excitation of tongue muscles. We developed a grid of 4×8 electrodes deposited over an adhesive 8- μ m thick polyurethane membrane. The testing protocol was conducted on 7 healthy participants and included functional tasks (vowels articulation and tongue movements) aimed at activating different regions of the tongue. The electrical stability of contact was assessed by measuring electrode-tongue impedances before and after the tasks. The spatial amplitude distribution of global EMG and single motor unit action potentials (MUAPs) was characterized. Electrode-tongue impedance magnitude showed no significant changes in the pre-post comparison ( 58±46 k Ω vs. 67±58 k Ω at 50Hz). Contact stability was confirmed by the quality of the signals that allowed to quantify spatiotemporal characteristics of muscle activation during the different tasks. The analysis of the spatial distribution of individual MUAPs amplitude showed that they were confined to relatively small areas on the tongue surface (range: 0.5cm2 -3.9cm [Formula: see text]. A variety of different spatiotemporal MUAP patterns, likely due to the presence of different muscle compartments with different fiber orientations, were observed. Our results demonstrate that the developed electrode grid enables HDsEMG acquisition from the tongue during functional tasks, thus opening new possibilities in tongue muscle assessment both at global and single motor unit level.

Characterization of cerebellar amyloid-β deposits in Alzheimer disease.

Cerebellar amyloid-β (Aβ) plaques are a component of the diagnostic criteria used in Thal staging and ABC scoring for Alzheimer disease (AD) neuropathologic change. However, Aβ deposits in this anatomic compartment are unique and under-characterized; and their relationship with other pathological findings are largely undefined. In 73 cases of pure or mixed AD with an A3 score in the ABC criteria, parenchymal (plaques) and vascular (cerebral amyloid angiopathy [CAA]) cerebellar Aβ-42 deposits were characterized with respect to localization, morphology, density, and intensity. Over 85% of cases demonstrated cerebellar Aβ-42 parenchymal staining that correlated with a Braak stage V-VI/B3 score (p < 0.01). Among the 63 with cerebellar Aβ-42 deposits, a diffuse morphology was observed in 75% of cases, compact without a central dense core in 32%, and compact with a central dense core in 16% (all corresponding to plaques evident on hematoxylin and eosinstaining). Cases with Purkinje cell (PC) loss showed higher proportions of PC layer Aβ-42 staining than cases without PC loss (88% vs 44%, p = 0.02), suggesting a link between Aβ-42 deposition and PC damage. Among all 73 cases, CAA was observed in the parenchymal vessels of 19% of cases and in leptomeningeal vessels in 44% of cases.

Differential in vivo labeling with barcoded antibodies allows for simultaneous transcriptomic profiling of airway, lung tissue and intravascular immune cells.

Single-cell RNA sequencing (scRNA-seq) is the state-of-the-art approach to study transcriptomic signatures in individual cells in respiratory health and disease. However, classical scRNA-seq approaches provide no spatial information and are performed using either bronchoalveolar lavage fluid (BAL) or lung single cell suspensions to assess transcript levels in airway and tissue immune cells, respectively. Herein we describe a simple method to simultaneously characterize transcriptomic features of airway, lung parenchymal and intravascular immune cells based on differential in vivo labeling with barcoded antibodies. In addition to gaining basic spatial information, this approach allows for direct comparison of cells within different anatomical compartments. Furthermore, this method provides a time- and cost-effective alternative to classical scRNA-seq where lung and BAL samples are processed individually, reducing animal and reagent use. We demonstrate the feasibility of this approach in a preclinical mouse model of bacterial lung infection comparing airway, parenchymal and vasculature neutrophils early after infection.

Predicting complex kidney drug handling using a physiologically-based pharmacokinetic model informed by biomarker-estimated secretory clearance and blood flow.

Kidney function-adjusted drug dosing is currently based solely on the estimated glomerular filtration rate (GFR), however, kidney drug handling is accomplished by a combination of filtration, tubular secretion, and re-absorption. Mechanistic physiologically-based pharmacokinetic (PBPK) models recapitulate anatomic compartments to predict elimination from estimated perfusion, filtration, secretion, and re-absorption, but clinical applications are limited by a lack of empiric individual-level measurements of these functions. We adapted and validated a PBPK model to predict drug clearance from individual biomarker-based estimates of kidney perfusion and secretory clearance. We estimated organic anion transporter-mediated secretion via kynurenic acid clearance and kidney blood flow (KBF) via isovalerylglycine clearance in human participants, incorporating these measurements with GFR into the model to predict kidney drug clearance. We compared measured and model-predicted clearances of administered tenofovir and oseltamivir, which are cleared by both filtration and secretion. There were 27 outpatients (age 55 ± 15 years, mean iohexol-GFR [iGFR] 76 ± 31 mL/min/1.73 m2 ) in this drug clearance study. The mean observed and mechanistic model-predicted tenofovir clearances were 169 ± 102 mL/min and 163 ± 80 mL/min, respectively; estimated mean error of the mechanistic model was 37.1 mL/min (95% confidence interval [CI]: 24-52.9), compared to a mean error of 41.8 mL/min (95% CI: 25-61.6) from regression model. The mean observed and model-predicted oseltamivir carboxylate clearances were 183 ± 104 mL/min and 179 ± 89 mL/min, respectively; estimated mean error of the mechanistic model was 42.9 mL/min (95% CI: 29.7-56.4), versus error of 48.1 mL/min (95% CI: 31.2-67.3) from the regression model. Individualized estimates of tubular secretion and KBF improved the accuracy of PBPK model-predicted tenofovir and oseltamivir kidney clearances, suggesting the potential for biomarker-informed measures of kidney function to refine personalized drug dosing.

Muscle Architecture of Leg Muscles: Functional and Clinical Significance.

Architectural properties of the muscles are the prime predictors of functional attributes and force-generating capacity of the muscles. This data is vital for musculoskeletal modelling and selecting the appropriate muscle-tendon units for tendon transfers.Cadaveric data for architectural properties is the gold standard and primary input for musculoskeletal modelling. There is a paucity of these datasets, especially in the leg muscles. Sixty muscles of the anterior and lateral compartments from twelve formalin-fixed lower limbs were studied for gross architecture, including the peculiar fibre arrangements and architectural properties of muscles. Muscle weight, muscle length, fibre length, pennation angle and sarcomere length were measured. Normalised fibre length, fibre length to muscle length ratio (FL/ML ratio), and the physiological cross-sectional area (PCSA) were calculated from the obtained data. Muscles displayed a combination of architectural strategies and were partly fusiform and partly pennate. The tibialis anterior and peroneus longus were the heaviest muscles in their respective compartments and showed more extensive origin from the nearby deep facial sheets.Long fibre length and less pennation angle were seen in muscles of the extensor compartment. Potential muscle power was highest in the tibialis anterior and peroneus longus and least in the extensor hallucis longus. Arching of the foot and eversion are peculiar to humans and recent in evolution. Due to the functional demand of maintaining the medial longitudinal arch and eversion, the tibialis anterior and peroneus longus have more muscle weight and larger physiological cross-sectional area and are potentially more powerful.Extensor compartment muscles were architecturally more suited for excursions because of the long fibre length and less pennation angle.This study contributes baseline normative data for musculoskeletal modelling platforms and simulation tools - an emerging area in biomechanics and tendon transfers.

Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy

HIV-1 reservoir cells that circulate in peripheral blood during suppressive antiretroviral therapy (ART) have been well characterized, but little is known about the dissemination of HIV-1-infected cells across multiple anatomical tissues, especially the CNS. Here, we performed single-genome, near full-length HIV-1 next-generation sequencing to evaluate the proviral landscape in distinct anatomical compartments, including multiple CNS tissues, from 3 ART-treated participants at autopsy. While lymph nodes and, to a lesser extent, gastrointestinal and genitourinary tissues represented tissue hotspots for the persistence of intact proviruses, we also observed intact proviruses in CNS tissue sections, particularly in the basal ganglia. Multi-compartment dissemination of clonal intact and defective proviral sequences occurred across multiple anatomical tissues, including the CNS, and evidence for the clonal proliferation of HIV-1-infected cells was found in the basal ganglia, in the frontal lobe, in the thalamus and in periventricular white matter. Deep analysis of HIV-1 reservoirs in distinct tissues will be informative for advancing HIV-1 cure strategies.

Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy.

HIV-1 reservoir cells that circulate in peripheral blood during suppressive antiretroviral therapy (ART) have been well characterized, but little is known about the dissemination of HIV-1-infected cells across multiple anatomical tissues, especially the CNS. Here, we performed single-genome, near full-length HIV-1 next-generation sequencing to evaluate the proviral landscape in distinct anatomical compartments, including multiple CNS tissues, from 3 ART-treated participants at autopsy. While lymph nodes and, to a lesser extent, gastrointestinal and genitourinary tissues represented tissue hotspots for the persistence of intact proviruses, we also observed intact proviruses in CNS tissue sections, particularly in the basal ganglia. Multi-compartment dissemination of clonal intact and defective proviral sequences occurred across multiple anatomical tissues, including the CNS, and evidence for the clonal proliferation of HIV-1-infected cells was found in the basal ganglia, in the frontal lobe, in the thalamus and in periventricular white matter. Deep analysis of HIV-1 reservoirs in distinct tissues will be informative for advancing HIV-1 cure strategies.

The coracobrachialis muscle: typical morphology, accessory forms, and the issues with terminology

The coracobrachialis muscle (CB) represents one of the anterior arm compartment muscles. It has been defined by classic anatomy textbooks and old papers, as a muscle of one belly arising from the coracoid process tip and partially from the tendon of the biceps brachii short head, and inserted into the humeral shaft, above the bone’s midpoint. However, recent cadaveric studies have confirmed that in the majority of cases, the CB is a two-headed muscle consisting of a superficial and a deep head. This finding has caused confusion regarding the terminology of CB’s morphology. Typical CB morphology, according to recent data should not be considered the muscle of one belly, but the two-headed muscle. In particular, the musculocutaneous nerve’s (MCN) course plays an important role in defining the CB morphological characteristics. If the MCN courses medially to the CB, with no signs of penetration after dissection, it can be concluded, that the CB is composed of one head; otherwise, if the muscle is composed of two or more heads, the MCN will courses between the CB bellies. In conclusion, it is of paramount importance to adopt common-universal terminology. Hence, considering recent findings, if the CB origin and/or the insertion differs from the typical anatomy, an “atypical CB” is the proper definition of the muscle, while if this “atypical CB” coexists with a typical CB, the terminology “accessory CB” may be used.

Characterization of Anthropometric Changes in Patients with Relapsed/Refractory Myeloma Treated with BCMA Bispecific Antibody Teclistamab

Introduction: Cancer-associated cachexia is associated with poor survival rates in several cancer types. Multiple Myeloma (MM) preferentially occurs in the elderly and is the most common cancer that causes lytic bone metastasis causing bone pain, fractures, mobility limitations, and falls. Cachexia is projected to be common in myeloma but has not been fully studied. Myeloma treatments including corticosteroids, radiation and alkylators cause muscle loss, while novel immunotherapy is tumor-specific but their impact on cachexia is unknown. We characterize the changes in body composition in patients with relapsed/refractory myeloma treated with BCMA bispecific antibody teclistamab and determine the association between body composition with treatement response and overall survival. Methods: 49 MM patients treated with teclistamab between 2000 and 2021 were included. All were with relapsed/refractory disease after &amp;gt; 4 lines of therapy and received an approved dose and schedule of teclistamab. The response assessment was according to IMWG criteria. Body weight, body mass index (BMI), tumor burden, and organ function were assessed at baseline and post-treatment. Standard-of-care abdominopelvic CT or PET/CT scans at baseline and at last known follow up were analyzed with Data Analysis Facilitation Suite (DAFS) software to quantify skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Differences between groups were tested using the χ 2 test or paired t-test. Progression free survival (PFS) and overall survival (OS) from the start of teclistamab to progression and death or last follow-up, respectively, were analyzed by the Kaplan-Meier method. Comparisons were made with the log-rank test. Results: Patient characteristics are detailed in Table 1. Based on the WHO definition, 2% were underweight, 16% were normal weight, 19% were overweight and 13% were obese, at baseline. The baseline mean SKM was 105.6 ± 27.8 (Male 122.0 ± 25.3, female 93.4 ± 23.5). SAT and VAT varied widely. Median SAT was 196.5 (range 48.3-558.6), and median VAT was 136.6 (33.09-448.1). Of 32 patients in the obese group, 16 (50%) patients had SKM that was below the mean SKM of the group. Baseline SAT and VAT, but not SKM were correlated with BMI. Twenty-seven of the 49 patients had paired imaging. The absolute changes in skeletal muscle and adipose tissue compartments are shown in Table 2. A majority of patients had a decline in SKM, SAT and VAT post-treatment: mean SKM decrease was 8.9 cm 2 ( p ≤ 0.01), mean SAT decreased 24.3 cm 2 ( p = 0.02) and mean VAT decreased 27.4 cm 2 ( p = 0.03), while BMI and weight were unchanged. Nineteen of 27 (70%) subjects responded to therapy. The changes in SKM, VAT, and SAT loss did not differ significantly between responders and non-responders. 38.8% of patients (19/49) had died by the end of the follow-up. Median follow-up duration was 2.8 years, overall survival was 1.7 years and PFS was 0.9 years. Baseline SKM, SAT, and VAT did not correlate with PFS or OS, but a decline in SMK significantly correlated with a shorter OS (p=0.04); 7/18 patients with decreased SKM and 2/9 patients with unchanged or increased SKM died. Response correlated strongly with overall survival (p=0.002). Conclusions: Body composition analysis of standard CT images may provide clinically relevant information for patients with advanced myeloma. Sarcopenia was common despite high BMI, and a further decline in skeletal muscle mass correlated with shorter survival, regardless of response to tumor-specific immunotherapy. Anthropometric changes should be validated in larger patient cohorts and included in future clinical trials. Further efforts should focus on the maintenance of muscle and visceral adipose tissue in this patient population.

Acute compartment syndrome of the lower limbs: Fasciotomy or dermofasciotomy? A cadaver study of compartment pressures

BackgroundAcute compartment syndrome (ACS) of the lower limbs is a function-threatening event usually managed by extended dermofasciotomy. Closure of the skin may be delayed, creating a risk of complications when there is an underlying fracture. Early treatment at the pre-ACS stage might allow isolated fasciotomy with no skin incision. The primary objective of this study was to compare intracompartmental pressure (ICP) changes after fasciotomy and after dermofasciotomy. The secondary objectives were to evaluate potential associations linking the starting ICP to achievement of an ICP below the physiological cut-off of 10mm Hg and to determine whether the ICP changes after fasciotomy and dermofasciotomy varied across muscle compartments. HypothesisFasciotomy with no skin incision may not provide a sufficient ICP decrease, depending on the initial ICP value. Material and methodsA previously validated model of cadaver ACS of the lower limbs was used. Saline was injected gradually to raise the ICP to>15mmHg (ICP15), >30mmHg (ICP30), and >50mmHg (ICP50). We studied 70 leg compartments (anterior, lateral, and superficial posterior) in 13 cadavers (mean age, 89.1±4.6years). ICP was monitored continuously. Percutaneous, minimally invasive fasciotomy consisting in one to three 1-cm incisions was performed in each compartment. ICP was measured before and after fasciotomy then after subsequent skin incision. The objective was to decrease the ICP below 10mmHg after fasciotomy or dermofasciotomy. ResultsOverall, mean ICP was 37.8±19.1mmHg after the injection of 184.0±133.01mL of saline. In the ICP15 group, the mean ICP of 16.1mmHg fell to 1.4mmHg after fasciotomy (ΔF=14.7) and 0.3mmHg after dermofasciotomy (ΔDF=1.1). Corresponding values in the ICP30 group were 33.9mmHg, 4.7mmHg (ΔF=29.2), and 1.2mmHg (ΔDF=3.5); and in the ICP50 group, 63.7mmHg, 17.0mmHg (ΔF=46.7), and 1.2mmHg (ΔDF=15.8). Thus, in the group with initial pressures >50mmHg, the ICP decrease was greater after both procedures, but fasciotomy alone nonetheless failed to achieve physiological values (<10mmHg). The pressure changes were not significantly associated with the compartment involved (anterior, lateral, or superficial posterior) (p<0.05). ConclusionUnder the conditions of this study, higher baseline ICPs were associated with larger ICP drops after fasciotomy and dermofasciotomy. Nevertheless, when the baseline ICP exceeded 50mmHg, fasciotomy alone failed to decrease the ICP below 10mmHg. Adding a skin incision achieved this goal. Level of evidenceIV, experimental study.

The Role of the Microenvironment and Cell Adhesion Molecules in Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy whose progression largely depends on the lymph node and bone marrow microenvironment. Indeed, CLL cells actively proliferate in specific regions of these anatomical compartments, known as proliferation centers, while being quiescent in the blood stream. Hence, CLL cell adhesion and migration into these protective niches are critical for CLL pathophysiology. CLL cells are lodged in their microenvironment through a series of molecular interactions that are mediated by cellular adhesion molecules and their counter receptors. The importance of these adhesion molecules in the clinic is demonstrated by the correlation between the expression levels of some of them, in particular CD49d, and the prognostic likelihood. Furthermore, novel therapeutic agents, such as ibrutinib, impair the functions of these adhesion molecules, leading to an egress of CLL cells from the lymph nodes and bone marrow into the circulation together with an inhibition of homing into these survival niches, thereby preventing disease progression. Several adhesion molecules have been shown to participate in CLL adhesion and migration. Their importance also stems from the observation that they are involved in promoting, directly or indirectly, survival signals that sustain CLL proliferation and limit the efficacy of standard and novel chemotherapeutic drugs, a process known as cell adhesion-mediated drug resistance. In this respect, many studies have elucidated the molecular mechanisms underlying cell adhesion-mediated drug resistance, which have highlighted different signaling pathways that may represent potential therapeutic targets. Here, we review the role of the microenvironment and the adhesion molecules that have been shown to be important in CLL and their impact on transendothelial migration and cell-mediated drug resistance. We also discuss how novel therapeutic compounds modulate the function of this important class of molecules.

Deep Learning Models Capture Histological Disease Activity in Crohn's Disease and Ulcerative Colitis with High Fidelity.

Histological disease activity in inflammatory bowel disease [IBD] is associated with clinical outcomes and is an important endpoint in drug development. We developed deep learning models for automating histological assessments in IBD. Histology images of intestinal mucosa from phase 2 and phase 3 clinical trials in Crohn's disease [CD] and ulcerative colitis [UC] were used to train artificial intelligence [AI] models to predict the Global Histology Activity Score [GHAS] for CD and Geboes histopathology score for UC. Three AI methods were compared. AI models were evaluated on held-back testing sets, and model predictions were compared against an expert central reader and five independent pathologists. The model based on multiple instance learning and the attention mechanism [SA-AbMILP] demonstrated the best performance among competing models. AI-modelled GHAS and Geboes subgrades matched central readings with moderate to substantial agreement, with accuracies ranging from 65% to 89%. Furthermore, the model was able to distinguish the presence and absence of pathology across four selected histological features, with accuracies for colon in both CD and UC ranging from 87% to 94% and for CD ileum ranging from 76% to 83%. For both CD and UC and across anatomical compartments [ileum and colon] in CD, comparable accuracies against central readings were found between the model-assigned scores and scores by an independent set of pathologists. Deep learning models based upon GHAS and Geboes scoring systems were effective at distinguishing between the presence and absence of IBD microscopic disease activity.

Are Different Modes of Weight Loss Associated with Survival in Oropharyngeal Cancer?

Patients with oropharyngeal squamous cell carcinomas (OPSCC) often lose weight during radical radiotherapy (RT). Nutritional intervention is required in case of severe weight loss. However, weight loss does not provide full insight into body composition changes. Muscle mass is emerging as an important prognostic factor in cancer patients. We employed on-treatment cone-beam CT (CBCT) scans to monitor muscle mass and weight loss under the hypothesis that different modes of weight loss exist and may impact overall survival (OS). A retrospective analysis of 197 OPSCC patients treated with definitive or adjuvant (chemo)RT. Weekly weight measurements & CBCTs were collected. Patients were included if at least two time-points were available and the interval between the first and last was between 15-50 days. CBCTs were normalized to account for calibration differences between treatment machines. An in-house deep-learning model automatically segmented the skeletal muscle compartment at C3 on all CBCTs. Segmentations were visually checked and failures removed. Skeletal muscle volume (SMV, in mm3) was extracted after thresholding for intra-muscular fat. Relative changes in weight & SMV were then calculated. Linear models were fitted to each trajectory for every patient and slopes were estimated. The following weight & SMV categories were defined to generate equal groups: lost (more than 0.4 standard deviations (SDs) below the mean (M)), maintained (within +/- 0.4 SDs of M) or gained (more than 0.4 SDs above the M). Table 1 highlights the nine modes of body composition change. The prognostic value of these was investigated in multivariable Cox models accounting for age, sex, disease stage, oropharynx subsite, smoking status, performance status (PS), tumor p16 status, baseline weight & SMV, and treatment prescribed. The primary endpoint was OS. Mean weight & SMV changes during treatment were -0.047±0.001% & -0.044±0.019% per day. In multivariable analysis, gaining weight & losing SMV was identified as a significant risk factor for OS (p = 0.01, hazard ratio [95% CI]: 4.59 [1.40-15.10]). In this sub-group, mean weight & SMV change were +0.054±0.008% & -0.396±0.030% per day. PS>2 (p<0.001) & lower baseline weight (p = 0.02) were also significantly associated with OS. Patients losing substantial SMV but mildly gaining weight have significantly worse OS than others. This suggests there exists a group of patients where nutritional support is needed, but not offered because they maintain weight during treatment. Although our results need validation, continual monitoring of muscle condition during RT would allow these patients to be identified and promptly targeted for nutritional support.