Arthroscopic capsular release is more effective in pain relief than conservative treatment in patients with frozen shoulder.

BACKGROUND: Frozen shoulder is a common medical condition, but the ideal therapeutic method is yet to be determined. Our aim was to analyze the pain-relieving effect of different treatment options used for the management of this disease. METHODS: Medical records of 59 patients (22 male, 37 female, average age: 55.5 years ±9.9) with early stage primary frozen shoulder were evaluated, their demographic data, physical examination, concomitant diseases and treatment specific data were registered. Life quality and the level of pain were assessed using the Oxford Shoulder Score (OSS) and Numeric Rating Scale (NRS). Different treatment modalities and their effect on pain relief were recorded. Any existing correlation between life quality, pain and demographic data, concomitant diseases or the therapeutic method used was investigated. RESULTS: The level of pain measured on NRS improved from 7.9 ± 1.6 to 1.9 ± 2.2. The most effective therapeutic method in terms of pain relief was surgery, followed by physiotherapy and intraarticular steroid injection (NRS score after treatment: 2 - p < 0.0001; 3.3 - p < 0.0001; 4.9 - p < 0.0001, respectively). Non-steroidal anti-inflammatory drugs (NSAIDs) did not reduce pain significantly. OSS improved from 24 to 43.6 and was not affected by the investigated variables, time to recovery was not influenced by the demographic data, the type of treatment or concomitant diseases. CONCLUSIONS: Arthroscopic capsular release, physiotherapy and intraarticular steroid injection outperformed physical therapy and NSAID treatment in terms of pain relief. Despite of slight but persistent post-therapeutic pain found in half of the cases, treatment was considered satisfactory by the patients. Nor patient specific neither therapy specific data had a significant effect on the course of the disease.

Business Risk Mitigation in the Development Process of New Monoclonal Antibody Drug Conjugates for Cancer Treatment.

Recent developments aim to extend the cytotoxic effect and therapeutic window of mAbs by constructing antibody-drug conjugates (ADCs), in which the targeting moiety is the mAb that is linked to a highly toxic drug. According to a report from mid of last year, the global ADCs market accounted for USD 1387 million in 2016 and was worth USD 7.82 billion in 2022. It is estimated to increase in value to USD 13.15 billion by 2030. One of the critical points is the linkage of any substituent to the functional group of the mAb. Increasing the efficacy against cancer cells' highly cytotoxic molecules (warheads) are connected biologically. The connections are completed by different types of linkers, or there are efforts to add biopolymer-based nanoparticles, including chemotherapeutic agents. Recently, a combination of ADC technology and nanomedicine opened a new pathway. To fulfill the scientific knowledge for this complex development, our aim is to write an overview article that provides a basic introduction to ADC which describes the current and future opportunities in therapeutic areas and markets. Through this approach, we show which development directions are relevant both in terms of therapeutic area and market potential. Opportunities to reduce business risks are presented as new development principles.

[Reducing the risk of radiation-induced cardiotoxicity in patients with left breast tumor]. / A sugárkezelés okozta cardiotoxicitas kockázatának csökkentése bal oldali emlotumoros betegek kezelése során.

INTRODUCTION: Breast cancer is one of the most common malignancies affecting women. Treatment with drugs and radiotherapy increases the incidence of late cardiovascular disease. It is therefore particularly important to protect the heart from radiation exposure. METHOD: We prepared an irradiation plan for 45 patients with left breast cancer using deep breathing and normal breathing techniques. The plans were compared and analyzed. The irradiation plans were created in the Philips Pinnacle v. 16 planning system. RESULTS: At the same target volume coverage, the use of the deep breathing technique leads to a reduction of the dose burden to the heart and to the left descending coronary branch, thus reducing the incidence of late cardiovascular complications. DISCUSSION: The results obtained show that the use of the deep breathing technique during adjuvant radiotherapy of left-sided breast cancer patients has a beneficial effect on the radiation exposure of the heart. Our results are in good agreement with similar data from national centres. We were not only able to maintain planning target volume coverage, but also to achieve an improvement of 1%. There is a significant difference in dose to the heart and coronary artery. By using the deep breathing technique, we were able to reduce the average cardiac dose by almost half (deep breathing: 2.87 Gy, normal breathing: 5.4 Gy). The coronary exposure was reduced from 19.5 Gy to 10.98 Gy. CONCLUSION: The accuracy of treatment can be further improved by using a respiratory gating system with a surface-guided radiotherapy system. The successful use of deep breathing technique requires professionalism of the treatment staff and good patient cooperation. It is less equipment intensive than a respiration-guided system. The deep breathing technique is no longer considered state-of-the-art in the era of breath-holding, but the experience gained in our department is worth describing because of its relevance to oncocardiology. Orv Hetil. 2023; 164(11): 420-425.

[Introduction of high-precision stereotactic body radiotherapy of lung tumors at Markusovszky Hospital]. / Tüdodaganatok nagy pontosságú stereotaxiás kezelésének bevezetése a Markusovszky Kórházban.

INTRODUCTION: A new, modern computed tomograph simulator was installed in the Oncology Department of the Markusovsky University Teaching Hospital from September 2021. The computed tomography simulator not only makes the work of specialists easier with its automatic contouring tool, but is also able to produce four-dimensional computed tomography scans. This facility is essential for radiotherapy of lung and breast cancer patients. OBJECTIVE: In this paper, we briefly review lung tumors and their treatment options, focusing on radiotherapy requiring high precision. We summarize patient selection criteria, the quality assurance processes for planning and treatment, and the experience gained in treating patients. METHOD: 5 patients were selected for our study. Their disease met the following criteria: 1 nodule, tumor diameter not exceeding 5 cm, patient was inoperable or negated surgery. The planning computed tomography scan was performed with Siemens Somatom go.Sim. At each respiratory phase, the tumor conturs were drawn and then aggregated as an integrated volume and an irradiation plan was prepared on this image. The treatments were performed on a Varian TrueBeam accelerator. RESULTS: Before each treatment, an adjusting CT scan was taken. The higher dose (4 × 12 Gy) treatment caused a reduction in tumor size on the last adjustment scan. DISCUSSION: Stereotaxic treatment, which is already available in Szombathely, may be a good alternative in the treatment of patients with inoperable lung cancer. The method is not burdensome for patients: fewer sessions, short treatment time. CONCLUSION: In the future, we would like to improve the accelerator with a breath capture system, which will allow even more precise treatment. Orv Hetil. 2022; 163(52): 2079-2087.

Thick-Filament Extensibility in Intact Skeletal Muscle.

Myofilament extensibility is a key structural parameter for interpreting myosin cross-bridge kinetics in striated muscle. Previous studies reported much higher thick-filament extensibility at low tension than the better-known and commonly used values at high tension, but in interpreting mechanical studies of muscle, a single value for thick-filament extensibility has usually been assumed. Here, we established the complete thick-filament force-extension curve from actively contracting, intact vertebrate skeletal muscle. To access a wide range of tetanic forces, the myosin inhibitor blebbistatin was used to induce low tetanic forces in addition to the higher tensions obtained from tetanic contractions of the untreated muscle. We show that the force/extensibility curve of the thick filament is nonlinear, so assuming a single value for thick-filament extensibility at all force levels is not justified. We also show that independent of whether tension is generated passively by sarcomere stretch or actively by cross-bridges, the thick-filament extensibility is nonlinear. Myosin head periodicity, however, only changes when active tension is generated under calcium-activated conditions. The nonlinear thick-filament force-extension curve in skeletal muscle, therefore, reflects a purely passive response to either titin-based force or actomyosin-based force, and it does not include a thick-filament activation mechanism. In contrast, the transition of myosin head periodicity to an active configuration appears to only occur in response to increased active force when calcium is present.

Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle.

Nebulin is a giant sarcomeric protein that spans along the actin filament in skeletal muscle, from the Z-disk to near the thin filament pointed end. Mutations in nebulin cause muscle weakness in nemaline myopathy patients, suggesting that nebulin plays important roles in force generation, yet little is known about nebulin's influence on thin filament structure and function. Here, we used small-angle X-ray diffraction and compared intact muscle deficient in nebulin (using a conditional nebulin-knockout, Neb cKO) with control (Ctrl) muscle. When muscles were activated, the spacing of the actin subunit repeat (27 Å) increased in both genotypes; when converted to thin filament stiffness, the obtained value was 30 pN/nm in Ctrl muscle and 10 pN/nm in Neb cKO muscle; that is, the thin filament was approximately threefold stiffer when nebulin was present. In contrast, the thick filament stiffness was not different between the genotypes. A significantly shorter left-handed (59 Å) thin filament helical pitch was found in passive and contracting Neb cKO muscles, as well as impaired tropomyosin and troponin movement. Additionally, a reduced myosin mass transfer toward the thin filament in contracting Neb cKO muscle was found, suggesting reduced cross-bridge interaction. We conclude that nebulin is critically important for physiological force levels, as it greatly stiffens the skeletal muscle thin filament and contributes to thin filament activation and cross-bridge recruitment.

Lateral gradients significantly enhance static magnetic field-induced inhibition of pain responses in mice--a double blind experimental study.

Recent research demonstrated that exposure of mice to both inhomogeneous (3-477 mT) and homogeneous (145 mT) static magnetic fields (SMF) generated an analgesic effect toward visceral pain elicited by the intraperitoneal injection of 0.6% acetic acid. In the present work, we investigated behavioral responses such as writhing, entry avoidance, and site preference with the help of a specially designed cage that partially protruded into either the homogeneous (ho) or inhomogeneous (inh) SMF. Aversive effects, cognitive recognition of analgesia, and social behavior governed mice in their free locomotion between SMF and sham sides. The inhibition of pain response (I) for the 0-5, 6-20, and 21-30 min periods following the challenge was calculated by the formula I = 100 (1 - x/y) in %, where x and y represent the number of writhings in the SMF and sham sides, respectively. In accordance with previous measurements, an analgesic effect was induced in exposed mice (Iho = 64%, P < 0.0002 and Iinh = 62%, P < 0.002). No significant difference was found in the site preference (SMFho, inh vs. sham) indicating that SMF is neither aversive nor favorable. Comparison of writhings observed in the sham versus SMF side of the cage revealed that SMF exposure resulted in significantly fewer writhings than sham (Iho = 64%, P < 0.004 and Iinh = 81%, P < 0.03). Deeper statistical analysis clarified that the lateral SMF gradient between SMF and sham sides could be responsible for most of the analgesic effect (Iho = 91%, P < 0.02 and Iinh = 54%, P < 0.02).

[Quality control of computed tomography scanners from the viewpoint of radiotherapy planning in Hungary]. / Computertomográfiás készülékek minôségellenôrzése a besugárzástervezés szempontjai alapján (Magyarországi helyzetelemzés).

The aim of this publication is to review the requirements necessary for using computed tomography (CT) for radiotherapy treatment planning. The equipments were tested with different CT phantoms. The authors made several measurements for checking the CT number, the quality and the mechanical parameters of CT tables. The CT numbers measured on the equipments of different manufacturers were in quite good agreement with the IAEA requirements. The geometric distortions of CT images are negligible, while the mechanical parameters of CT tables show considerable variety. A quality assurance - quality control protocol is recommended to implement in a safe workflow.

Quality Control of Portal Imaging with PTW EPID QC PHANTOM.

PURPOSE: Quality assurance (QA) and quality control (QC) of different electronic portal imaging devices (EPID) and portal images with the PTW EPID QC PHANTOM. MATERIAL AND METHODS: Characteristic properties of images of different file formats were measured on Siemens OptiVue500aSi, Siemens BeamView Plus, Elekta iView, and Varian PortalVision and analyzed with the epidSoft 2.0 program in four radiation therapy centers. The portal images were taken with Kodak X-OMAT V and the Kodak Portal Localisation ReadyPack films and evaluated with the same program. RESULTS: The optimal exposition both for EPIDs and portal films of different kind was determined. For double exposition, the 2+1 MU values can be recommended in the case of Siemens OptiVue500aSi Elekta iView and Kodak Portal Localisation ReadyPack films, while for Siemens BeamView Plus, Varian PortalVision and Kodak X-OMAT V film 7+7 MU is recommended. CONCLUSION: The PTW EPID QC PHANTOM can be used not only for amorphous silicon EPIDs but also for images taken with a video-based system or by using an ionization chamber matrix or for portal film. For analysis of QC tests, a standardized format (used at the acceptance test) should be applied, as the results are dependent on the file format used.