Tissue Reaction Research Articles

Ex Vivo Histological Analysis of Corneas with Manually Implanted Intracorneal Stromal Ring Segments.

Backgrond: Intracorneal ring segments (ICRSs) are utilized to correct refractive changes impacting visual acuity, commonly implanted via femtosecond laser but can also inserted manually. Corneal deposits alongside the ICRS channels are seen commonly. Methods: This study explores the histological characteristics of corneal deposits following manual ICRS implantation, comparing them to previously published articles describing femtosecond laser-assisted cases. Results: This is a retrospective analysis of three cases involving manual ICRS implantation, accumulation of whitish deposits and later explanation of the corneas due to penetrating keratoplasty (PKP). Patient demographics, ocular history, and surgical details were collected. Histological analysis employed Hematoxylin and Eosin (H&E) and Masson's trichrome staining. Whitish deposits along ICRS tracts were observed in all cases, with minimal fibroblastic transformation of keratocytes adjacent to the segments. Comparing these cases of manual to femtosecond laser-assisted ICRS implantation, in most cases, similar deposits were identified, indicating the deposits' association with the stromal tissue reaction to the ring segment and not to the surgical technique. Conclusions: This study contributes insights into the histopathology of manually implanted ICRS, emphasizing the shared nature of deposits in both insertion methods. The findings highlight the link between deposits and the stromal tissue reaction to the ring segment, irrespective of the insertion technique.

Stromal-cellular remodeling of breast tissue after silicone implant damage

One of the current vectors of modern reconstructive and cosmetic surgery is augmentation mammoplasty - an operation to enlarge the mammary glands. The breast implant is well tolerated by the body, as the immunogenicity of its material is extremely low. At the same time, the silicone gel of the implant is a foreign object and the surrounding breast tissues give a stereotypical response in the form of growth of the connective tissue stroma with the formation of a capsule around the implant and the appearance of focal cellular infiltrates. Modern breast implants, unlike implants of previous decades, are more sophisticated in their structure, and the level of protection against damage is much higher. A complication associated with the long-term use (up to 20 years) of implants, where low-quality silicone or industrial silicone was used as a filler, is the penetration of low-molecular-weight particles of the implant through its shell to the surrounding tissues with the subsequent formation of silicone granules. In the vast majority, such changes develop after mechanical traumatization of the implant. The purpose of the study is to establish the morphological criteria of the reaction of breast tissue after silicone implant damage. The material for research was histological micropreparations of breast tissue from the archive of the "Grace Clinic" (Kyiv), with the mutual consent of patients who applied for repeated mammoplasty. The duration of the implants in the breast gland was from 6 to 20 years. The age range of the women was from 36 to 53 years. On preparations stained with hematoxylin and eosin, tissue biopsies of the glands of 9 patients with a diagnosis of deformation of silicone implants and violation of the integrity of their wall were presented. The micropreparations were visualized using a UlabXSP-137TLED light microscope at various magnifications and photographed with an XCAM 1080P camera. The study of histological preparations of soft tissues of the breast glands, from which silicone implants were removed, established changes in stromal-cellular elements, namely: decorated fibrous structures accumulated in the form of dense capsules with elements of local contractures; from the side of cellular elements, the most demonstrative were cellular infiltrates, which included macrophages, lymphocytes, and plasma cells, which indicated a high probability of a chronic inflammatory process. A large number of giant multinucleated cells of foreign bodies were present in practically all examined sections, which indicated the impossibility of macrophages to complete phagocytosis with lysis of the phagocytosed material, which by its chemical composition is the silicone of the implant. All the described phenomena can be interpreted as a natural reaction of the tissues to the implant, the contents of which got into the soft tissues of the breast. Thus, the presence of numerous giant multinucleated cells of foreign bodies, dense capsules with elements of local contractures, and a significant predominance of macrophages, lymphocytes, and plasma cells in cellular infiltrates over other cellular elements can be considered a morphological criterion for the reaction of breast tissue to silicone implant damage.

Implantable conductive polymer bioelectrode with enzymatic antioxidant activity for enhanced tissue responses and in vivo performance

Implantable bioelectrodes enable precise diagnosis and treatment through direct transmission of electrical signals in the living tissues. However, a fundamental challenge arises as implanted bioelectrodes frequently lose performance due to adverse tissue reactions, primarily induced by high oxidative stress and subsequent inflammatory activation of macrophages. In this study, we investigated a novel strategy to address this challenge in implantable bioelectrodes by introducing reactive oxygen species (ROS)-scavenging capabilities to the bioelectrodes. Specifically, a polypyrrole (PPy) electrode doped with hemin-conjugated heparin (HepH) was fabricated to impart robust enzyme-like antioxidant properties. The HepH-doped PPy electrodes exhibited a catalase-mimicking activity, as evidenced by hydrogen peroxide scavenging and oxygen gas generation in the presence of hydrogen peroxide. In vitro primary macrophage culture and in vivo subcutaneous implantation studies revealed that HepH-incorporated PPy electrodes reduced intracellular ROS levels and directed macrophage polarization toward an anti-inflammatory phenotype, mitigating collagenous scar tissue formation around the implanted electrodes. Finally, real-time electrocardiogram monitoring for 20 days demonstrated the extended in vivo signal sensitivity of the HepH-doped PPy electrodes as reliable implantable bioelectrodes.

3D-printed resin composite posterior fixed dental prosthesis: a prospective clinical trial up to 1 year

ObjectivesThis clinical trial evaluated the clinical behavior of 3D-printed posterior resin composite fixed dental prostheses (FDPs).Materials and methodsBetween 10 October 2020 and 5 August 2022, 49 patients aged 19–60 years (16 men, 33 women) received 68 3D-printed resin composite 3-unit posterior FDPs (ELS Even Stronger, Saremco, Switzerland). FDPs were followed up 2 weeks after placement (baseline), 6 months after placement, and 1 year after placement by two independent calibrated observers using modified FDI criteria for anatomical form, secondary caries, marginal adaptation, surface roughness, color match, fracture of material, staining surface, staining margin, approximate anatomical form, retention, gingival health, and patient's view. Survival analyses were performed using Kaplan–Meier analyses.ResultsA total of 59 restorations were evaluated and the mean observation period was 8.63 months. Failure types were categorized as mechanical and biological. Failures were observed in 14 FDPs. Nine FDPs showed mechanical failure and five FDPs showed biological failure. Mechanical failures were mostly experienced as connector fractures. Eight FDPs showed cohesive fractures (seven in a single connector at either at the mesial or distal and one in the pontic itself). Biological failures, including root canal treatment and gingival tissue reactions, were observed within the first 6 months. Based on mechanical failures, the survival rate was 86.7% including the biological complications; this corresponded to 71.6% (Kaplan–Meier). After 1 year, two FDPs showed surface luster loss (score 4), two-color mismatches (score 4), and two-surface staining (score 4).Conclusion3D-printed resin composite FDPs were observed acceptable after 1 year of clinical follow-up, providing that the experienced failure types were mainly associated with fractures in the connector region, which requires revision of design parameters.Clinical Trial RegistrationClinical Trials.Gov, NCT04600297.

Galacturonic acid-capsaicin prodrug for prolonged nociceptive-selective nerve blockade

There is an urgent clinical need to develop nerve-blocking agents capable of inducing long duration sensory block without muscle weakness or paralysis to treat post-operative and chronic pain conditions. Here, we report a galacturonic acid-capsaicin (GalA-CAP) prodrug as an effective nociceptive-selective axon blocking agent. Capsaicin selectively acts on nociceptive signaling without motor nerve blockade or disruption of proprioception and touch sensation, and the galacturonic acid moiety enhance prodrug permeability across the restrictive peripheral nerve barriers (PNBs) via carrier-mediated transport by the facilitative glucose transporters (GLUTs). In addition, following prodrug transport across PNBs, the inactive prodrug is converted to active capsaicin through linker hydrolysis, leading to sustained drug release. A single injection of GalA-CAP prodrug at the sciatic nerves of rats led to nociceptive-selective nerve blockade lasting for 234 ± 37 h, which is a sufficient duration to address the most intense period of postsurgical pain. Furthermore, the prodrug markedly mitigated capsaicin-associated side effects, leading to a notable decrease in systemic toxicity, benign local tissue reactions, and diminished burning and irritant effects.

Neurotoxic effects of triclosan in adolescent mice: Pyruvate kinase M2 dimer regulated Signal transducer and activator of transcription 3 phosphorylation mediated microglia activation and neuroinflammation

Triclosan (TCS), a commonly used antibacterial agent, is associated with various harmful effects on mammalian neurodevelopment, particularly when exposed prenatally. This study investigated the impact of long-term exposure to TCS on the prefrontal cortex development in adolescent mice. We evaluated the motor ability, motor coordination, and anxiety behavior of mice using open field tests (OFT) and elevated cross maze tests (EPM). An increase in movement distance, number of passes through the central area, and open arm retention time was observed in mice treated with TCS. Hematoxylin eosin staining and Nissl staining also showed significant adverse reactions in the brain tissue of TCS-exposed group. TCS induced microglia activation and increased inflammatory factors expression in the prefrontal cortex. TCS also increased the expression of pyruvate kinase M2 (PKM2), thereby elevating the levels of PKM2 dimer, which entered the nucleus. Treatment with TEPP46 (PKM2 dimer nuclear translocation inhibitor) blocked the expression of inflammatory factors induced by TCS. TCS induced the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3) in vivo and in vitro, upregulating the levels of inflammatory cytokines. The results also demonstrated the binding of PKM2 to STAT3, which promoted STAT3 phosphorylation at the Tyr705 site, thereby regulating the expression of inflammatory factors. These findings highlight the role of PKM2-regulated STAT3 phosphorylation in TCS-induced behavioral disorders in adolescents and propose a reliable treatment target for TCS.

Periodontal considerations during orthodontic intrusion and extrusion in healthy and reduced periodontium.

In patients with advanced periodontal disease, pathological tooth migration may occur, which may require subsequent orthodontic treatment for both aesthetic and functional purposes. When planning orthodontic treatment mechanics, intrusive or extrusive forces are frequently indicated. Understanding tissue reactions during these movements is essential for clinicians when devising a comprehensive orthodontic-periodontal treatment plan. This knowledge enables clinicians to be fully aware of and account for the potential effects on the surrounding tissues. The majority of our understanding regarding the behavior of periodontal tissues in both healthy and compromised periodontal conditions is derived from animal studies. These studies offer the advantage of conducting histological and other assessments that would not be feasible in human research. Human studies are nevertheless invaluable in being able to understand the clinically relevant response elicited by the periodontal tissues following orthodontic tooth movement. Animal and human data show that in dentitions with reduced periodontal support, orthodontic intrusion of the teeth does not induce periodontal damage, provided the periodontal tissues do not have inflammation and plaque control with excellent oral hygiene is maintained. On the contrary, when inflammation is not fully controlled, orthodontic intrusion may accelerate the progression of periodontal destruction, with bacterial plaque remnants being displaced subgingivally, leading to further loss of attachment. Orthodontic extrusion, on the other hand, does not seem to cause further periodontal breakdown in dentitions with reduced periodontal support, even in cases with deficient plaque control. This is attributed to the nature of the tooth movement, which directs any plaque remnants coronally (supragingivally), reducing the risk of adverse effects on the periodontal tissues. This specific type of tooth movement can be leveraged to benefit periodontal conditions by facilitating the regeneration of lost hard and soft periodontal tissues in a coronal direction. As a result, orthodontic extrusion can be employed in implant site development, offering an advantageous alternative to more invasive surgical procedures like bone grafting. Regardless of the tooth movement prescribed, when periodontal involvement is present, it is essential to prioritize periodontal therapy before commencing orthodontic treatment. Adequate plaque control is also imperative for successful outcomes. Additionally, utilizing light orthodontic forces is advisable to achieve efficient tooth movement while minimizing the risk of adverse effects, notably root resorption. By adhering to these principles, a more favorable and effective combined orthodontic-periodontal approach can be ensured. The present article describes indications, mechanisms, side effects, and histological and clinical evidence supporting orthodontic extrusion and intrusion in intact and reduced periodontal conditions.

Injectable hydrogel based on liposome self-assembly for controlled release of small hydrophilic molecules

Controlled release of low molecular weight hydrophilic drugs, administered locally, allows maintenance of high concentrations at the target site, reduces systemic side effects, and improves patient compliance. Injectable hydrogels are commonly used as a vehicle. However, slow release of low molecular weight hydrophilic drugs is very difficult to achieve, mainly due to a rapid diffusion of the drug out of the drug delivery system. Here we present an injectable and self-healing hydrogel based entirely on the self-assembly of liposomes. Gelation of liposomes, without damaging their structural integrity, was induced by modifying the cholesterol content and surface charge. The small hydrophilic molecule, sodium fluorescein, was loaded either within the extra-liposomal space or encapsulated into the aqueous cores of the liposomes. This encapsulation strategy enabled the achievement of controlled and adjustable release profiles, dependent on the mechanical strength of the gel. The hydrogel had a high mechanical strength, minimal swelling, and slow degradation. The liposome-based hydrogel had prolonged mechanical stability in vivo with benign tissue reaction. This work presents a new class of injectable hydrogel that holds promise as a versatile drug delivery system. Statement of significanceThe porous nature of hydrogels poses a challenge for delivering small hydrophilic drug, often resulting in initial burst release and shorten duration of release. This issue is particularly pronounced with physically crosslinked hydrogels, since their matrix can swell and dissipate rapidly, but even in cases where the polymers in the hydrogel are covalently cross-linked, small molecules can be rapidly released through its porous mesh. Here we present an injectable self-healing hydrogel based entirely on the self-assembly of liposomes. Small hydrophilic molecules were entrapped inside the extra-liposomal space or loaded into the aqueous cores of the liposomes, allowing controlled and tunable release profiles.

Long-Term Outcomes of a Percutaneous Wide-Diameter Bone-Anchored Hearing Implant: A Clinical Evaluation of More than 800 Implants.

This study evaluates the clinical outcomes of 807 percutaneous wide-diameter bone-anchored hearing implants (BAHIs) in 701 patients. In addition, it compares patient groups and examines bone conduction device (BCD) usage. Retrospective cohort study. Mean follow-up period of 3.8 years. Tertiary referral center. All patients implanted with a percutaneous wide-diameter BAHI until December 2020 were included. Patients were divided into age groups, "loading-time" groups, and, if applicable, specific subgroups thought to be at risk for complications postsurgery, e.g., intellectual disability and comorbidities. Soft tissue reaction, implant survival, revision surgery, and BCD usage. In 9.1% of the 5,188 observations of 807 implants, an adverse soft tissue reaction was reported according to the Holgers' scale. Significantly more (adverse) soft tissue reactions were observed in children and intellectually disabled (ID) patients (p < 0.05). Comorbidity subgroups showed no significant differences in soft tissue reactions. Implant loss percentage, including explantations, was 6.2%. Implant survival was significantly worse in patients with ID (14.1%; p = 0.021). Pediatric age, early loading, or comorbidities did not significantly influence implant survival. At least 592 implants (73.4%) were used for bone conduction hearing, of which 65.4% were used daily. Both children and ID patients are more prone to (adverse) soft tissue reactions, ID patients only have a higher risk of implant loss. The rate of implant loss in children seemed to be reduced compared to previous studies and thus more comparable to adults since using wide-diameter implants.

Electrochemical Study and Mechanical Properties of Ti-Zr Alloy for Biomedical Applications

In response to concerns of potential cytotoxicity and adverse tissue reactions caused by vanadium and aluminum in the currently used biomaterial Ti-6Al-4V, the Ti–20Zr alloy was evaluated in this study because it has been suggested as a candidate for human body implant material. The Ti-20Zr alloy was obtained by vacuum-melting, followed by heat treatment at 1000 °C for 1 h, and then air-cooled. Optical and scanning electron microscopy revealed that the sample had an α and β lamellar microstructure. Analysis showed that the mechanical properties, in terms of hardness measurements performed at low loads, were significantly different between the two phases. Thus, it was found out that the α phase is softer by about 30% compared to the β phase. The Electrochemical Impedance Spectroscopy technique (EIS) was employed to study the electrochemical behavior in simulated body fluid (SBF). The electrochemical behavior demonstrated that Ti-20Zr alloy exhibits excellent corrosion resistance due to the stable oxide layer formed on its surface. SEM and EDS investigations showed that the surface topography, after electrochemical studies, is characterized by a porous film with increased oxygen content, which might be suitable for the osteoinductive growth of bone.

Acute hematologic toxicity prediction using dosimetric and radiomics features in patients with cervical cancer: does the treatment regimen matter?

Acute hematologic toxicity (HT) is a prevalent adverse tissue reaction observed in cervical cancer patients undergoing chemoradiotherapy (CRT), which may lead to various negative effects such as compromised therapeutic efficacy and prolonged treatment duration. Accurate prediction of HT occurrence prior to CRT remains challenging. A discovery dataset comprising 478 continuous cervical cancer patients (140 HT patients) and a validation dataset consisting of 205 patients (52 HT patients) were retrospectively enrolled. Both datasets were categorized into the CRT group and radiotherapy (RT)-alone group based on the treatment regimen, i.e., whether chemotherapy was administered within the focused RT duration. Radiomics features were derived by contouring three regions of interest (ROIs)-bone marrow (BM), femoral head (FH), and clinical target volume (CTV)-on the treatment planning CT images before RT. A comprehensive model combining the radiomics features as well as the demographic, clinical, and dosimetric features was constructed to classify patients exhibiting acute HT symptoms in the CRT group, RT group, and combination group. Furthermore, the time-to-event analysis of the discriminative ROI was performed on all patients with acute HT to understand the HT temporal progression. Among three ROIs, BM exhibited the best performance in classifying acute HT, which was verified across all patient groups in both discovery and validation datasets. Among different patient groups in the discovery dataset, acute HT was more precisely predicted in the CRT group [area under the curve (AUC) = 0.779, 95% CI: 0.657-0.874] than that in the RT-alone (AUC = 0.686, 95% CI: 0.529-0.817) or combination group (AUC = 0.748, 95% CI: 0.655-0.827). The predictive results in the validation dataset similarly coincided with those in the discovery dataset: CRT group (AUC = 0.802, 95% CI: 0.669-0.914), RT-alone group (AUC = 0.737, 95% CI: 0.612-0.862), and combination group (AUC = 0.793, 95% CI: 0.713-0.874). In addition, distinct feature sets were adopted for different patient groups. Moreover, the predicted HT risk of BM was also indicative of the HT temporal progression. HT prediction in cervical patients is dependent on both the treatment regimen and ROI selection, and BM is closely related to the occurrence and progression of HT, especially for CRT patients.

Effect of fractional picosecond laser therapy using a diffractive optical lens on histological tissue reaction

ABSTRACT Background and Objectives Fractional ablative resurfacing techniques are preferred treatments for facial rejuvenation of aged skin. This study was performed to investigate the cutaneous effects of using a fractional picosecond laser at 1064 nm with a diffractive lens. Methods The penetration depth according to the location of the handpiece tip was evaluated using an acrylic panel. Laser induced optical breakdown (LIOB) and cutaneous damage were observed after hematoxylin and eosin staining in guinea pigs. Collagen formation was evaluated using Victoria staining, Masson’s trichrome (MT) staining, and immunohistochemical staining for collagen type III. Results The penetration depth for LEVEL 1 was 499.98–935.23 μm (average: 668.75 ± 182.84 μm); the LIOB cavity area was 1664.17 ± 650.52 μm2. The penetration depth of LEVEL 2 was 257.12–287.38 μm (average: 269.77 ± 14.55 μm) with an LIOB cavity area of 1335.85 ± 214.41 μm2. At LEVEL 3, that was 36.17–53.69 μm (average: 52.15 ± 20.81 μm) and the LIOB cavity area was 1312.67 ± 1069.12 μm2. No epidermal tissue damage was observed and collagen formation was observed from day 14 under all conditions. Conclusion Diffractive optical element (DOE) lens arranged laser treatment system controlled the position of LIOB occurrence and an irradiating area.

Induction of Peroxiredoxin 1 by Hypoxia Promotes Cellular Autophagy and Cell Proliferation in Oral Leukoplakia via HIF-1α/BNIP3 Pathway.

Hypoxia is a key trigger in the transformation of oral leukoplakia into oral cancer. However, it is still too early to determine the role of hypoxia in the development of oral leukoplakia. Prx1, an antioxidant protein, upregulated by hypoxia, regulates cellular autophagy in leukoplakia. This study aimed to understand the mechanisms by which hypoxia induces Prx1 expression during autophagy in oral leukoplakia. We used an experimental model of tongue epithelial hyperplasia induced by 4-nitroquinoline-1-oxide (4NQO) and dysplastic oral keratinocytes. Prx1 knockdown DOK cells, Leuk-1 cells and control cells were harvested, and cell proliferation was assayed using the Cell Counting Kit-8. Several hypoxia and autophagy-related proteins were examined using quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and western blotting in cells and mouse tongue tissues. In addition, the ultrastructure of the cells was observed by transmission electron microscopy. Hypoxia induces cell proliferation, autophagic vesicles and the expression of Prx1, BNIP3, LC3II/I and Beclin-1 in DOK and Leuk-1 cells. However, these effects were all attenuated by Prx1 knockdown. Histologically, 4NQO induced epithelial hyperplasia in the tongue mucosa. The expression of proliferation marker PCNA, autophagy-related proteins LC3B and Beclin-1, as well as HIF-1α/BNIP3 was significantly lower in the tongue tissues of Prx1flox/flox:Cre+ mice compared with Prx1flox/flox mice. In Prx1flox/flox:Cre+ mice, an increased expression of HIF-1α/BNIP3, LC3B and Beclin-1 was detected in epithelial hyperplasia tongue tissues compared to normal tissues. The current study suggests that Prx1 may promotes cell proliferation and autophagy in oral leukoplakia cells via the HIF-1α/BNIP3 pathway.

Failure Following Revision Total Hip Arthroplasty After Cobalt-Chrome Femoral Heads are Placed on a Retained Femoral Stem

BackgroundFailure due to trunnionosis with adverse local tissue reaction (ALTR) has been reported with cobalt-chrome (CoCr) heads in total hip arthroplasty (THA); however, there are limited data on the use of these heads in the revision setting. The purpose of this study was to analyze the outcomes of patients who underwent revision THA with a retained femoral component and received a CoCr femoral head on a used trunnion. MethodsIn this retrospective review, we identified all patients who underwent revision THA with a retained femoral component and received a CoCr femoral head between February 2006 and March 2014. Demographic factors, implant details, and postoperative complications, including the need for repeat revisions, were recorded. In total, 107 patients were included (mean age 67 years, 74.0% women). Of the 107 patients, 24 (22.4%) required repeat revisions. ResultsPatients who required repeat revision were younger than those who did not (mean age: 62.9 versus 69, P = .03). The most common indications for repeat revision were instability (8 of 24, 33.3%), ALTR (5 of 24, 20.8%), and infection (4 of 18, 16.7%). Evidence of ALTR or metallosis was identified at the time of reoperation in 10 of the 24 patients who underwent re-revision (41.7%). ConclusionsThe placement of a new CoCr femoral head on a used trunnion during revision THA with a retained femoral component carries a significant risk of complication (22.4%) and should be avoided when possible.

Edaravone Alleviates Traumatic Brain Injury by Inhibition of Ferroptosis via FSP1 Pathway.

Traumatic brain injury (TBI) is a highly severe form of trauma with complex series of reactions in brain tissue which ultimately results in neuronal damage. Previous studies proved that neuronal ferroptosis, which was induced by intracranial haemorrhage and other reasons, was one of the most primary causes of neuronal damage following TBI. However, the association between neuronal mechanical injury and ferroptosis in TBI and relevant treatments remain unclear. In the present study, we first demonstrated the occurrence of neuronal ferroptosis in the early stage of TBI and preliminarily elucidated that edaravone (EDA), a cerebroprotective agent that eliminates oxygen radicals, was able to inhibit ferroptosis induced by TBI. A cell scratching model was established in PC12 cells, and it was confirmed that mechanical injury induced ferroptosis in neurons at the early stage of TBI. Ferroptosis suppressor protein 1 (FSP1) plays a significant role in inhibiting ferroptosis, and we found that iFSP, a ferroptosis agonist which is capable to inhibit FSP1 pathway, attenuated the anti-ferroptosis effect of EDA. In conclusion, our results suggested that EDA inhibited neuronal ferroptosis induced by mechanical injury in the early phase of TBI by activating FSP1 pathway, which could provide evidence for future research on prevention and treatment of TBI.

Simultaneous integrated boost intensity-modulated radiotherapy post breast-conserving surgery: clinical efficacy, adverse effects, and cosmetic outcomes in breast cancer patients

BackgroundSimultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) is an innovative technique delivering a higher dose to the tumor bed while irradiating the entire breast. This study aims to assess the clinical outcomes, adverse effects, and cosmetic results of SIB-IMRT following breast-conserving surgery in breast cancer patients.MethodsWe conducted a retrospective analysis of 308 patients with stage 0–III breast cancer who underwent breast-conserving surgery and SIB-IMRT from January 2016 to December 2020. The prescribed doses included 1.85 Gy/27 fractions to the whole breast and 2.22 Gy/27 fractions or 2.20 Gy/27 fractions to the tumor bed. Primary endpoints included overall survival (OS), local–regional control (LRC), distant metastasis-free survival (DMFS), acute and late toxicities, and cosmetic outcomes.ResultsThe median follow-up time was 36 months. The 3-year OS, LRC, and DMFS rates were 100%, 99.6%, and 99.2%, respectively. Five patients (1.8%) experienced local recurrence or distant metastasis, and one patient succumbed to distant metastasis. The most common acute toxicity was grade 1–2 skin reactions (91.6%). The most common late toxicity was grade 0–1 skin and subcutaneous tissue reactions (96.7%). Five patients (1.8%) developed grade 1–2 upper limb lymphedema, and three patients (1.1%) had grade 1 radiation pneumonitis. Among the 262 patients evaluated for cosmetic outcomes at least 2 years post-radiotherapy, 96.9% achieved excellent or good results, while 3.1% had fair or poor outcomes.ConclusionsSIB-IMRT after breast-conserving surgery in breast cancer patients demonstrated excellent clinical efficacy, mild acute and late toxicities, and satisfactory cosmetic outcomes in our study. SIB-IMRT appears to be a feasible and effective option for breast cancer patients suitable for breast-conserving surgery.

Very Early Loading of a Bone-Anchored Hearing System Is Safe.

To investigate the feasibility of early sound processor loading with two separate bone-anchored hearing aid implants 1 to 2 weeks after implantation. Secondary endpoints included registration of any postoperative complications, skin reactions, and any adverse events. Prospective, nonrandomized, noncontrolled, multicenter clinical trial. Tertiary referral center. Sixty adult patients, eligible for bone-anchored hearing aid surgery, were enrolled. Implantation of the bone-anchored hearing aid implants were done using minimally invasive surgery with tissue preservation. Implant stability quotient (ISQ) values were recorded using resonance frequency analysis. Follow-ups were scheduled 5 to 12 days, 4 to 8 weeks, 6 months, and 12 months postoperatively. Differences between the lowest ISQ values (ISQ low) over time were analyzed by paired-samples t test with a significance level of 0.05. Skin and soft tissue reactions were assessed according to Holger's classification. Loading time of the Ponto Wide implant was 11.6 ± 1.4 days (SD) in average (median, 12 d; range, 7-19 d). Loading of the Ponto BHX implant was done 9.7 ± 3.5 days (SD) postoperatively (median, 9 d; range, 5-19 d). The implant stability increased significantly during the 12-month study period with both implants. One Ponto BHX implant was lost. Skin and soft tissue reactions were few in both groups. Across all planned follow-up visits, no skin and soft tissue reactions were observed in 86% (Ponto BHX implant) and 85% (Ponto Wide implant). Very early loading of sound processors after percutaneous bone-anchored hearing system surgery is safe already 1 to 2 weeks postoperatively.

Effect of Stevioside (Stevia rebaudiana) on Entamoeba histolytica Trophozoites.

Human amoebiasis still represents a major health problem worldwide. Metronidazole has been used as the most common drug to treat the disease; however, it is also known that the drug causes undesirable side effects. This has led to the search for new pharmacological alternatives which include phytochemical compounds with antiamoebic effects. We analyzed the amoebicidal activity of stevioside (STV), a diterpene glycoside present in Stevia rebaudiana, on trophozoites of E. histolytica. Different concentrations of STV were tested, and an inhibitory concentration of 50% of cell viability (IC50) was determined with an exposition of 9.53 mM for 24 h. Trophozoites exposed to STV showed morphological changes evidenced by the decrease in the basic structures related to the movement and adherence to the substrate, as well as ultrastructural features characterized by a loss of regularity on the cell membrane, an increase in cytoplasmic granularity, and an increase in apparent autophagic vacuoles. Also, the decrease in cysteine protease expression and the proteolytic activity of trophozoites to degrade the cell monolayer were analyzed. A histological analysis of hamster livers inoculated with trophozoites and treated with STV showed changes related to the granulomatous reaction of the liver parenchymal tissue. Our results constitute the first report related to the possible use of STV as a therapeutic alternative in amoebiasis.

Utilization of a highly adaptable murine air pouch model for minimally invasive testing of the inflammatory potential of biomaterials.

Introduction: The biocompatibility of an implanted material strongly determines the subsequent host immune response. After insertion into the body, each medical device causes tissue reactions. How intense and long-lasting these are is defined by the material properties. The so-called foreign body reaction is a reaction leading to the inflammation and wound healing process after implantation. The constantly expanding field of implant technology and the growing areas of application make optimization and adaptation of the materials used inevitable. Methods: In this study, modified liquid silicone rubber (LSR) and two of the most commonly used thermoplastic polyurethanes (TPU) were compared in terms of induced inflammatory response in the body. We evaluated the production of inflammatory cytokines, infiltration of inflammatory cells and encapsulation of foreign bodies in a subcutaneous air-pouch model in mice. In this model, the material is applied in a minimally invasive procedure via a cannula and in one piece, which allows material testing without destroying or crushing the material and thus studying an intact implant surface. The study design includes short-term (6h) and long-term (10days) analysis of the host response to the implanted materials. Air-pouch-infiltrating cells were determined by flow cytometry after 6h and 10days. Inflammation, fibrosis and angiogenesis markers were analyzed in the capsular tissue by qPCR after 10days. Results: The foreign body reaction was investigated by macroscopic evaluation and scanning electron microscopy (SEM). Increased leukocyte infiltration was observed in the air-pouch after 6h, but it markedly diminished after 10days. After 10days, capsule formations were observed around the materials without visible inflammatory cells. Discussion: For biocompatibility testing materials are often implanted in muscle tissue. These test methods are not sufficiently conclusive, especially for materials that are intended to come into contact with blood. Our study primarily shows that the presented model is a highly adaptable and minimally invasive test system to test the inflammatory potential of and foreign body reaction to candidate materials and offers more precise analysis options by means of flow cytometry.

A murine model of peanut-allergic asthma.

Peanut allergy is an IgE-mediated food allergy that is associated with asthma in certain patients. With increasing prevalence, its great impact on the quality of life, and a lack of treatment options, the need for new therapy options is a given. Hence, models for research and development are required. This study aimed to establish a murine model of allergic airway inflammation induced by peanut allergens. C3H mice were sensitised by intraperitoneal injections of peanut allergen extract and challenged by an intranasal application of the same extract. The assessment of airway inflammation involved the analysis of immune cells in the bronchoalveolar lavage fluid as measured by flow cytometry. Inflammatory reactions in the lung tissue were also studied by histology and quantitative PCR. Moreover, peanut-specific immune responses were studied after re-stimulation of spleen cells in vitro. Sensitisation led to allergen-specific IgE, IgA, and IgG1 seroconversion. Subsequent nasal exposure led to allergic airway inflammation as manifested by structural changes such as bronchial smooth muscle hypertrophy, mucus cell hyperplasia, infiltration of eosinophil cells and T cells, as well as an upregulation of genes expressing IL-4, IL-5, IL-13, and IFN-γ. Upon re-stimulation of splenocytes with peanut allergen, increased secretion of both T-helper type 2 (Th2) and Th1 cytokines was observed. We successfully established a peanut-associated asthma model that exhibited many features characteristic of airway inflammation in human patients with allergic asthma. The model holds potential as a tool for investigating novel therapeutic approaches aimed at preventing the development of allergic asthma.