Cortical and Trabecular Bone Modeling and Implications for Bone Functional Adaptation in the Mammalian Tibia.

Bone modeling involves the addition of bone material through osteoblast-mediated deposition or the removal of bone material via osteoclast-mediated resorption in response to perceived changes in loads by osteocytes. This process is characterized by the independent occurrence of deposition and resorption, which can take place simultaneously at different locations within the bone due to variations in stress levels across its different regions. The principle of bone functional adaptation states that cortical and trabecular bone tissues will respond to mechanical stimuli by adjusting (i.e., bone modeling) their morphology and architecture to mechanically improve their mechanical function in line with the habitual in vivo loading direction. This principle is relevant to various research areas, such as the development of improved orthopedic implants, preventative medicine for osteopenic elderly patients, and the investigation of locomotion behavior in extinct species. In the present review, the mammalian tibia is used as an example to explore cortical and trabecular bone modeling and to examine its implications for the functional adaptation of bones. Following a short introduction and an exposition on characteristics of mechanical stimuli that influence bone modeling, a detailed critical appraisal of the literature on cortical and trabecular bone modeling and bone functional adaptation is given. By synthesizing key findings from studies involving small mammals (rodents), large mammals, and humans, it is shown that examining both cortical and trabecular bone structures is essential for understanding bone functional adaptation. A combined approach can provide a more comprehensive understanding of this significant physiological phenomenon, as each structure contributes uniquely to the phenomenon.

Chronic postsurgical pain (CPSP): an underestimated problem after incisional hernia treatment.

BACKGROUND: Chronic postsurgical pain (CPSP) is a potential long-term problem following open incisional hernia repair which may affect the quality of life of patients despite successful anatomical repair of the hernia. The aim of this manuscript was to identify the incidence and outcome of patients following open incisional hernia repair in respect of risk factors to develop CPSP. METHODS: A single-center retrospective analysis of patients who underwent open incisional hernia repair between 2015 and 2021 was performed. Pre-existing conditions (e.g., diabetes mellitus and malignancy), hernia complexity, postoperative complications, and postoperative pain medication were analyzed using the local database. Quality of life and CPSP were assessed using the EuraHS Quality of Life (QoL) questionnaire. RESULTS: A total of 182 cases were retrospectively included in a detailed analysis based on the complete EuraHS (QoL) questionnaire. During the average follow-up period of 46 months, this long-term follow-up revealed a 54.4% incidence of CPSP and including a rate of 14.8% for severe CPSP (sCPSP) after open incisional hernia surgery. The complexity of the hernia and the demographic variables were not different between the group with and without CPSP. Patients with CPSP reported significantly reduced QoL. The analgesics score which includes the need of pain medication in the initial days after surgery was significantly higher in patients with CPSP than in those without (no CPSP: 2.86 vs. CPSP: 3.35; p = 0.047). CONCLUSION: The presence of CPSP after open incisional hernia repair represents a frequent and underestimated long-term problem which has been not been recognized to this extent before. CPSP impairs QoL in these patients. Patients at risk to develop CPSP can be identified in the perioperative setting by the need of high doses of pain medication using the analgesics score. Possibly timely adjustment of pain medication, even in the domestic setting, could alleviate the chronicity or severity of CPSP.

Morphological examination of abdominal vertebral bodies from grass carp using high-resolution micro-CT scans.

The vertebral column, a defining trait of all vertebrates, is organized as a concatenated chain of vertebrae, and therefore its support to the body depends on individual vertebral morphology. Consequently, studying the morphology of the vertebral centrum is of anatomical and clinical importance. Grass carp (GC) is a member of the infraclass Teleostei (teleost fish), which accounts for the majority of all vertebrate species; thus, its vertebral anatomical structure can help us understand vertebrate development and vertebral morphology. In this study, we have investigated the morphology and symmetry of the grass carp vertebral centrum using high-resolution micro-CT scans. To this end, three abdominal vertebrae (V9, V10, & V11) from eight grass carp were micro-CT scanned and then segmented using Dragonfly (ORS Inc.). Grass carp vertebral centrum conformed to the basic teleost pattern and demonstrated an amphicoelous shape (biconcave hourglass). The centrum's cranial endplate was smaller, less circular, and shallower compared to the caudal endplate. While the vertebral centrum demonstrated bilateral symmetry along the sagittal plane (left/right), the centrum focus was shifted dorsally and cranially, breaking dorsoventral and craniocaudal symmetry. The sum of these findings implies that the caudal aspect of grass carp vertebral centrum is bigger and more robust. Currently, we have no information whether this is due to nature, for example, differences in gene expression, or nurture, for example, environmental effect. As the vertebral parapophyses and spinous processes are slanted caudally, the direction of muscle action during swimming may create a gradient of stresses from cranial to caudal, resulting in a more robust caudal aspect of the vertebral centrum. Expanding our study to include additional quadrupedal and bipedal (i.e., human) vertebrae, as well as testing if these morphological aspects of the vertebrae are indeed plastic and can be affected by environmental factors (i.e., temperature or other stressors) may help answer this question.

The trabecular architecture of the popliteal sesamoid bone (cyamella) from a New Zealand white rabbit (Oryctolagus cuniculus).

Sesamoid bones are ossified structures that are embedded in tendons near articulation. They consist of an inner trabecular bone architecture surrounded by a thin cortical shell. While the formation of sesamoid bones is probably mainly controlled by genetic factors, the proper development and mineralization of a sesamoid bone depends also on mechanical stimulation. While most sesamoid bones are not loaded directly by other bones during locomotion, they still experience forces directed from the tendon in which they are embedded. In cases when the sesamoid bone is experiencing forces only from a single tendon, such as the cyamella in the rabbit, this may give us a tool to study bone functional adaptation in a relatively simple loading setting. This study investigates the internal trabecular architecture of the popliteal sesamoid bone (cyamellae) in New Zealand white (NZW) rabbits (Oryctolagus cuniculus). Five hind limbs of NZW rabbits were micro-computed tomography scanned and the cortical and trabecular architectures of the cyamellae were evaluated. The results revealed that similar to the patella, the cyamella has a thin cortex and a high trabecular bone volume fraction (BV/TV), which is derived mostly from the high trabecular thickness (Tb.Th). Trabecular BV/TV and Tb.Th were not distributed homogeneously, but they were lower at the periphery and higher closer to the proximal and middle of the cyamella, near the musculotendinous junction. The results also demonstrated that trabeculae tend to align along two recognizable orientations, one with the direction of tensile stresses, in line with the popliteal tendon, and the second bridging the narrow space between the cranial and caudal cortical faces of the bone.

Postoperative Analgesics Score as a Predictor of Chronic Postoperative Inguinal Pain After Inguinal Hernia Repair: Lessons Learned From a Retrospective Analysis.

BACKGROUND: Chronic postoperative inguinal pain (CPIP) is a common complication after inguinal hernia surgery and occurs in up to 10-14% of cases. CPIP has a significant impact on daily life, work ability and thus compromises quality of life. The aim of this retrospective study was an in-depth analysis of patients undergoing inguinal hernia repair to further refine the prediction of the onset of CPIP reliably. METHODS: A single center retrospective analysis of patients with who underwent open or minimally invasive inguinal hernia repair from 2016 to 2021 was carried out. Complication rates, detailed analysis of postoperative pain medication and quality of life using the EuraHS Quality of Life questionnaire were assessed. RESULTS: Out of 596 consecutive procedures, 344 patients were included in detailed analyses. While patient cohorts were different in terms of age and co-morbidities, and the prevalence of CPIP was 12.2% without differences between the surgical procedures (Lichtenstein: 12.8%; TEP 10.9%; TAPP 13.5%). Postoperative pain was evaluated using a newly developed analgesic score. Patients who developed CPIP later had a significant higher consumption of analgesics at discharge (p = 0.016). As additional risk factors for CPIP younger patient age and postoperative complications were identified. CONCLUSION: The prospective use of the analgesic score established here could be helpful to identify patients that are at risk to develop CPIP. These patients could benefit from a structured follow-up to allow early therapeutic intervention to prevent chronification and restore the quality of life.

High-Throughput Screen for Inhibitors of Klebsiella pneumoniae Virulence Using a Tetrahymena pyriformis Co-Culture Surrogate Host Model.

The continuing emergence of antibacterial resistance reduces the effectiveness of antibiotics and drives an ongoing search for effective replacements. Screening compound libraries for antibacterial activity in standard growth media has been extensively explored and may be showing diminishing returns. Inhibition of bacterial targets that are selectively important under in vivo (infection) conditions and, therefore, would be missed by conventional in vitro screens might be an alternative. Surrogate host models of infection, however, are often not suitable for high-throughput screens. Here, we adapted a medium-throughput Tetrahymena pyriformis surrogate host model that was successfully used to identify inhibitors of a hyperviscous Klebsiella pneumoniae strain to a high-throughput format and screened circa 1.2 million compounds. The screen was robust and identified confirmed hits from different chemical classes with potent inhibition of K. pneumoniae growth in the presence of T. pyriformis that lacked any appreciable direct antibacterial activity. Several of these appeared to inhibit capsule/mucoidy, which are key virulence factors in hypervirulent K. pneumoniae. A weakly antibacterial inhibitor of LpxC (essential for the synthesis of the lipid A moiety of lipopolysaccharides) also appeared to be more active in the presence of T. pyriformis, which is consistent with the role of LPS in virulence as well as viability in K. pneumoniae.

Secondary osteon structural heterogeneity between the cranial and caudal cortices of the proximal humerus in white-tailed deer.

Cortical bone remodeling is an ongoing process triggered by microdamage, where osteoclasts resorb existing bone and osteoblasts deposit new bone in the form of secondary osteons (Haversian systems). Previous studies revealed regional variance in Haversian systems structure and possibly material, between opposite cortices of the same bone. As bone mechanical properties depend on tissue structure and material, it is predicted that bone mechanical properties will vary in accordance with structural and material regional heterogeneity. To test this hypothesis, we analysed the structure, mineral content and compressive stiffness of secondary bone from the cranial and caudal cortices of the white-tailed deer proximal humerus. We found significantly larger Haversian systems and canals in the cranial cortex but no significant difference in mineral content between the two cortices. Accordingly, we found no difference in compressive stiffness between the two cortices and thus our working hypothesis was rejected. As the deer humerus is curved and thus likely subjected to bending during habitual locomotion, we expect that similar to other curved long bones, the cranial cortex of the deer humerus is likely subjected primarily to tensile strains and the caudal cortex is subject primarily to compressive strains. Consequently, our results suggest that strain magnitude (larger in compression) and sign (compression versus tension) affect the osteoclasts and osteoblasts differently in the basic multicellular unit. Our results further suggest that osteoclasts are inhibited in regions of high compressive strains (creating smaller Haversian systems) while the osteoid deposition and mineralization by osteoblasts is not affected by strain magnitude and sign.

Are we crying Wolff? 3D printed replicas of trabecular bone structure demonstrate higher stiffness and strength during off-axis loading.

Roux's principle of bone functional adaptation postulates that bone tissue, and particularly trabecular bone tissue, responds to mechanical stimuli by adjusting (modeling) its architecture accordingly. Hence, it predicts that the new modeled trabecular structure is mechanically improved (stiffer and stronger) in line with the habitual in vivo loading direction. While previous studies found indirect evidence to support this theory, direct support was so far unattainable. This is attributed to the fact that each trabecular bone is unique, and that trabecular bone tissue tends to be damaged during mechanical testing. Consequently, a unique modeled trabecular structure can be mechanically tested only along one direction and a comparison to other directions for that specific structure is impossible. To address this issue, we have 3D printed 10 replicas of a trabecular structure from a sheep talus cropped along the 3 principal axes of the bone and in line with the principal direction of loading (denoted on-axis model). Next, we have rotated the same cropped trabecular structure in increments of 10° up to 90° to the bone principal direction of loading (denoted off-axis models) and printed 10 replicas of each off-axis model. Finally, all on-axis and off-axis 3D printed replicas were loaded in compression until failure and trabecular structure stiffness and strength were calculated. Contrary to our prediction, and conflicting with Roux's principle of bone functional adaptation, we found that a trabecular structure loaded off-axis tended to have higher stiffness and strength values when compared to the same trabecular structure loaded on-axis. These unexpected results may not disprove Roux's principle of bone functional adaptation, but they do imply that trabecular bone adaptation may serve additional purposes than simply optimizing bone structure to one principal loading scenario and this suggests that we still don't fully understand bone modeling in its entirety.

Assessing the discharge instructing in the emergency department: Patient perspective.

OBJECTIVE: The objective of the study is to assess how well the emergency department (ED) personnel succeed in instructing the patient at discharge. METHODS: In November and December 2016 at Peijas Hospital ED, Finland, a structured questionnaire was conducted during a phone interview on patients the day after discharge. RESULTS: A total of 132 patients interviewed. Ninety percent had received discharge instructions from the ED staff, most of them (75%) about medication. Almost half of the patients (45%) were satisfied with the communication at discharge, those not satisfied (47%) felt that the staff did not know enough of their background to give discharge instructions. Of the patients, 20% thought that they did not have the opportunity to ask questions during the guidance session, and 41% thought that the session was too short and restricted. Some patients (20%) felt that the instructions were ambiguous, but 63% (83/132) felt they were able to follow them well or very well. CONCLUSION: The pace of care in the ED is fast and duration of the stay is short. The patients must be able to take responsibility of their self-care. Failure to follow medical discharge instructions could lead to non-compliance. Attention should be paid to enhancing the quality of discharge instructing and the instructions provided by the ED personnel, as recurring visits and inquiry calls add to the ED workload.

Using principal trabecular orientation to differentiate joint loading orientation in the 3rd metacarpal heads of humans and chimpanzees.

If Wolff's law is valid, then quantifying the three-dimensional architecture of trabecular bone, specifically 3D principal trabecular orientation (3D-PTO), can reveal joint loading direction among different taxa. This study measured the architecture of trabecular bone in the 3rd metacarpal head of humans and chimpanzees, and then tested their association with expected joint loading direction. We postulate that since chimpanzees, unlike humans, directly load their metacarpal bones during knuckle-walking, trabecular structure in the dorsal aspect of the 3rd metacarpal head will be significantly more organized and robust in chimpanzees. To test this hypothesis, we micro-CT scanned the 3rd metacarpal from 11 chimpanzees and 12 humans. Three 6 mm volumes of interest (VOI; palmar, center and dorsal) were selected and trabecular bone properties and 3D-PTO were measured. The results revealed many similarities between humans and chimpanzees: in both taxa the dorsal VOI demonstrated the lowest bone volume fraction (BV/TV), the most rod-like trabecular structure, the fewest and thinnest trabeculae, and low organization of the trabecular architecture (degree of anisotropy). Nevertheless, 3D-PTO in the dorsal VOI differed significantly between humans and chimpanzees. While 3D-PTO in humans was clustered together and aligned nearly along the bone long axis, in chimpanzees 3D-PTO was divided into two distinct groups and aligned with an angle toward either the medial or lateral orientations. Our results suggest that loading effects on trabecular bone properties such as BV/TV might be partially constrained by genetic factors. On the other hand, 3D-PTO is continually affected by active loading (i.e., modeling) and thus may serve as a useful tool to infer differences in joint loading directions.

The orthotropic elastic properties of fibrolamellar bone tissue in juvenile white-tailed deer femora.

Fibrolamellar bone is a transient primary bone tissue found in fast-growing juvenile mammals, several species of birds and large dinosaurs. Despite the fact that this bone tissue is prevalent in many species, the vast majority of bone structural and mechanical studies are focused on human osteonal bone tissue. Previous research revealed the orthotropic structure of fibrolamellar bone, but only a handful of experiments investigated its elastic properties, mostly in the axial direction. Here we have performed for the first time an extensive biomechanical study to determine the elastic properties of fibrolamellar bone in all three orthogonal directions. We have tested 30 fibrolamellar bone cubes (2 × 2 × 2 mm) from the femora of five juvenile white-tailed deer (Odocoileus virginianus) in compression. Each bone cube was compressed iteratively, within its elastic region, in the axial, transverse and radial directions, and bone stiffness (Young's modulus) was recorded. Next, the cubes were kept for 7 days at 4 °C and then compressed again to test whether bone stiffness had significantly deteriorated. Our results demonstrated that bone tissue in the deer femora has an orthotropic elastic behavior where the highest stiffness was in the axial direction followed by the transverse and the radial directions (21.6 ± 3.3, 17.6 ± 3.0 and 14.9 ± 1.9 Gpa, respectively). Our results also revealed a slight non-significant decrease in bone stiffness after 7 days. Finally, our sample size allowed us to establish that population variance was much bigger in the axial direction than the radial direction, potentially reflecting bone adaptation to the large diversity in loading activity between individuals in the loading direction (axial) compared with the normal (radial) direction. This study confirms that the mechanically well-studied human transverse-isotropic osteonal bone is just one possible functional adaptation of bone tissue and that other vertebrate species use an orthotropic bone tissue structure which is more suitable for their mechanical requirements.

The symbiosis of contact force catheter use for hybrid ablation for atrial fibrillation.

OBJECTIVE: Reconduction across an ablation line is a common reason for arrhythmia recurrence over time. The hybrid procedure combines epicardial ablation of the pulmonary vein (PV) and creation of a box lesion with endocardial touch-ups for any electrical gaps. A high contact force (CF) between the ablation tip and cardiac tissue may increase the risk of thrombus formation, catheter tip charring, steam pop formation, and even cardiac perforation. CF monitoring is a significant new parameter for titration of the CF for creating an adequate lesion. METHODS: Thirty-eight consecutive patients underwent epicardial ablation using bipolar radiofrequency devices. After checking electrical bidirectional block of the ablation lines, an endocardial CF catheter was used for further ablation (if needed) to complete the isolation of PVs, box lesion, cavotricuspid isthmus (CTI), and complex fractionated atrial electrograms (CFAE). RESULTS: Endocardial touch-up was needed for 2 PVs (1.3 %) and 10 (26.3 %) box lesions. It was also used for the CTI line in 7 (18.4 %) patients, atrial tachycardia in 3 (7.9 %) patients, and additional CFAE ablation in 17 (44.7 %) patients. All 5 patients with arrhythmia recurrence had a mean CF < 10 g (p = 0.03). Procedure duration was significantly shorter in the CF group (223 ± 57 vs. 256 ± 60 min, p = 0.03) compared with control group. CONCLUSION: Use of CF catheters is safe, feasible, and complementary to a hybrid procedure setup for atrial fibrillation ablation. Its real-time monitoring may predict future arrhythmia recurrence, and decrease procedure time.

Measuring resting energy expenditure during extracorporeal membrane oxygenation: preliminary clinical experience with a proposed theoretical model.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with severe respiratory failure. Indirect calorimetry (IC) is a safe and non-invasive method for measuring resting energy expenditure (REE). No data exist on the use of IC in ECMO-treated patients as oxygen uptake and carbon dioxide elimination are divided between mechanical ventilation and the artificial lung. We report our preliminary clinical experience with a theoretical model that derives REE from IC measurements obtained separately on the ventilator and on the artificial lung. METHODS: A patient undergoing veno-venous ECMO for acute respiratory failure due to bilateral pneumonia was studied. The calorimeter was first connected to the ventilator and oxygen consumption (VO2 ) and carbon dioxide transport (VCO2 ) were measured until steady state was reached. Subsequently, the IC was connected to the membrane oxygenator and similar gas analysis was performed. VO2 and VCO2 values at the native and artificial lung were summed and incorporated in the Weir equation to obtain a REEcomposite . RESULTS: At the ventilator level, VO2 and VCO2 were 29.5 ml/min and 16 ml/min. VO2 and VCO2 at the artificial lung level were 213 ml/min and 187 ml/min. Based on these values, a REEcomposite of 1703 kcal/day was obtained. The Faisy-Fagon and Harris-Benedict equations calculated a REE of 1373 and 1563 kcal/day. CONCLUSION: We present IC-acquired gas analysis in ECMO patients. We propose to insert individually obtained IC measurements at the native and the artificial lung in the Weir equation for retrieving a measured REEcomposite .

The association of serotype and pulsed-field gel electrophoresis genotype in isolates of Streptococcus pneumoniae isolated in Israel.

The relationship between Streptococcus pneumoniae isolates causing invasive infections in children admitted to a single center in central Israel was examined by pulsed-field gel electrophoresis (PFGE) and serotyping. Although there was a close correlation between serotype and PFGE clone, the genetic diversity varied by serotype, with some genotypes comprising multiple serotypes. Additionally, clones C and D were associated with higher penicillin minimum inhibitory concentrations. Serotyping alone may be insufficient for epidemiological mapping of pneumococcal isolates in the era of pneumococcal conjugate polysaccharide vaccines.

[Is a different view on the pathophysiology of sepsis the key for novel therapeutic options?]. / Sepsis: neue Erkenntnisse, andere Perspektiven - neue Therapieoptionen?

Sepsis remains a critical problem in virtually all fields of clinical medicine. Despite intensive scientific and clinical efforts no significant progress has emerged in the fight against sepsis mortality. Solely the algorithm of the "surviving sepsis campaign" has proven to result in significantly enhanced survival of sepsis patients when consequently adopted. Novel research in the field of the complex immunological alterations in sepsis suggests that ongoing immunosuppression is the critical determinant underlying sepsis mortality. Therefore, it was proposed that immunostimulation might be a successful approach to improve outcome in individually selected patients. Others favor a different view on the pathophysiology of sepsis and support the notion that the manifestation of organ failure may be the dominant therapeutic target. Due to the fact that breakdown of the microcirculation and disruption of the microvascular barrier are critical events preceding organ failure, experimental therapeutic efforts to address these events led to promising results. Taken together, in view of the many initially promising experimental data and the failure to translate them into successful clinical therapies, a different view on the pathophysiology of sepsis is warranted to obtain the key for novel therapeutic options.

Trabecular evidence for a human-like gait in Australopithecus africanus.

Although the earliest known hominins were apparently upright bipeds, there has been mixed evidence whether particular species of hominins including those in the genus Australopithecus walked with relatively extended hips, knees and ankles like modern humans, or with more flexed lower limb joints like apes when bipedal. Here we demonstrate in chimpanzees and humans a highly predictable and sensitive relationship between the orientation of the ankle joint during loading and the principal orientation of trabecular bone struts in the distal tibia that function to withstand compressive forces within the joint. Analyses of the orientation of these struts using microCT scans in a sample of fossil tibiae from the site of Sterkfontein, of which two are assigned to Australopithecus africanus, indicate that these hominins primarily loaded their ankles in a relatively extended posture like modern humans and unlike chimpanzees. In other respects, however, trabecular properties in Au africanus are distinctive, with values that mostly fall between those of chimpanzees and humans. These results indicate that Au. africanus, like Homo, walked with an efficient, extended lower limb.

Extracardiac minimal invasive implantation of cardioverter defibrillator in young children.

Implantable cardioverter defibrillator (ICD) placement in young children remains a challenge due to device-patient size mismatch and the important choice between an endovenous or an epicardial approach for lead implantation. We treated three children, with respectively Long QT-syndrome, Brugada syndrome and Brugada syndrome with sick sinus syndrome, ranging from 9 months to 7 years with a subxyphoidal ICD and extracardiac lead implantation by minimally invasive techniques. In all cases the thresholds were excellent. The devices could be properly placed in the preperitoneal space without discomfort to the patients. The clinical course was uneventful and results were excellent.