Neoadjuvant therapy with immune checkpoint inhibitors in operable nonsmall cell lung cancer.

PURPOSE OF REVIEW: In localized nonsmall cell lung cancer (NSCLC) systemic recurrences after surgery are common. Therefore, adjuvant or neoadjuvant chemotherapy is used. With the advent of immune checkpoint inhibitors (ICIs) in metastatic disease the question is whether ICIs can further improve the outcome. RECENT FINDINGS: In several phase I/II trials, major pathological response (MPR) rates with several ICIs between 7% and 50% were seen. No major additional side effects occurred. In combination with chemotherapy CheckMate-816 randomized additional neoadjuvant nivolumab and achieved a high pathological complete response (pCR) rate and a better event-free survival (EFS) - without negatively influencing surgery. More randomized trials are performed with neoadjuvant immunochemotherapy and adjuvant treatment after surgery. In Keynote-671, pembrolizumab is used pre and postoperatively with a significantly higher EFS rate at 2 years (62.4% vs. 40.6%). Similar preliminary results are reported in the AEGEAN (durvalumab) and Neotorch (toripalimab) trials. Higher tumour stage and MPR, partly programmed cell death 1 ligand 1 (PD-L1) expression, tumour mutational burden (TMB) and circulating tumour DNA (ctDNA) are correlated with efficacy. SUMMARY: Neoadjuvant immunochemotherapy improves MPR and EFS rates, especially in more advanced tumours and tumours expressing PD-L1 - without relevantly increasing toxicities. But further and longer evaluation is needed.

Literature review: potential non-thermal molecular effects of external radiofrequency electromagnetic fields on cancer.

INTRODUCTION: There is an ongoing scientific discussion, that anti-cancer effects induced by radiofrequency (RF)-hyperthermia might not be solely attributable to subsequent temperature elevations at the tumor site but also to non-temperature-induced effects. The exact molecular mechanisms behind said potential non-thermal RF effects remain largely elusive, however, limiting their therapeutical targetability. OBJECTIVE: Therefore, we aim to provide an overview of the current literature on potential non-temperature-induced molecular effects within cancer cells in response to RF-electromagnetic fields (RF-EMF). MATERIAL AND METHODS: This literature review was conducted following the PRISMA guidelines. For this purpose, a MeSH-term-defined literature search on MEDLINE (PubMed) and Scopus (Elsevier) was conducted on March 23rd, 2024. Essential criteria herein included the continuous wave RF-EMF nature (3 kHz - 300 GHz) of the source, the securing of temperature-controlled circumstances within the trials, and the preclinical nature of the trials. RESULTS: Analysis of the data processed in this review suggests that RF-EMF radiation of various frequencies seems to be able to induce significant non-temperature-induced anti-cancer effects. These effects span from mitotic arrest and growth inhibition to cancer cell death in the form of autophagy and apoptosis and appear to be mostly exclusive to cancer cells. Several cellular mechanisms were identified through which RF-EMF radiation potentially imposes its anti-cancer effects. Among those, by reviewing the included publications, we identified RF-EMF-induced ion channel activation, altered gene expression, altered membrane potentials, membrane oscillations, and blebbing, as well as changes in cytoskeletal structure and cell morphology. CONCLUSION: The existent literature points toward a yet untapped therapeutic potential of RF-EMF treatment, which might aid in damaging cancer cells through bio-electrical and electro-mechanical molecular mechanisms while minimizing adverse effects on healthy tissue cells. Further research is imperative to definitively confirm non-thermal EMF effects as well as to determine optimal cancer-type-specific RF-EMF frequencies, field intensities, and exposure intervals.

Theoretical evaluation of the impact of diverse treatment conditions by calculation of the tumor control probability (TCP) of simulated cervical cancer Hyperthermia-Radiotherapy (HT-RT) treatments in-silico.

INTRODUCTION: Hyperthermia (HT) induces various cellular biological processes, such as repair impairment and direct HT cell killing. In this context, in-silico biophysical models that translate deviations in the treatment conditions into clinical outcome variations may be used to study the extent of such processes and their influence on combined hyperthermia plus radiotherapy (HT + RT) treatments under varying conditions. METHODS: An extended linear-quadratic model calibrated for SiHa and HeLa cell lines (cervical cancer) was used to theoretically study the impact of varying HT treatment conditions on radiosensitization and direct HT cell killing effect. Simulated patients were generated to compute the Tumor Control Probability (TCP) under different HT conditions (number of HT sessions, temperature and time interval), which were randomly selected within margins based on reported patient data. RESULTS: Under the studied conditions, model-based simulations suggested a treatment improvement with a total CEM43 thermal dose of approximately 10 min. Additionally, for a given thermal dose, TCP increased with the number of HT sessions. Furthermore, in the simulations, we showed that the TCP dependence on the temperature/time interval is more correlated with the mean value than with the minimum/maximum value and that comparing the treatment outcome with the mean temperature can be an excellent strategy for studying the time interval effect. CONCLUSION: The use of thermoradiobiological models allows us to theoretically study the impact of varying thermal conditions on HT + RT treatment outcomes. This approach can be used to optimize HT treatments, design clinical trials, and interpret patient data.

Pseudomembranous colitis as a complication in Covid-19.

OBJECTIVE: Aim: To improve the results of treatment of patients with pseudomembranous colitis against the background of coronavirus infection. PATIENTS AND METHODS: Materials and Methods: The study presents the results of a retrospective analysis of 96 patients with pseudomembranous colitis, who were treated in the infectious Covid department at the base of the Uzhhorod City Clinical Hospital since 2020 to 2022. The average age of patients was 55.2 years, there were 38 (39.5%) men and 58 (60.5%) women. Diagnosis of complications - pseudomembranous colitis (PMC) - was based on clinical data, ultrasound and CT of the abdominal organs, fibrocolonoscopy, laparoscopy. RESULTS: Results: The frequency of PMC from the total number of patients who were in hospital treatment (8205 patients) due to COVID-19 was 1.17%, and this indicator was 0.62% in 2020, and 2.28% in 2021. Indications for operative treatment were: colon perforation - 9.4% of patients; peritonitis (diffuse, widespread) without obvious perforation of the colon wall - 85.5% of patients; mesenteric thrombosis - 4.1% of patients. In the case of perforation of the colon, resection of the colon was performed with the formation of a proximal colostomy and ileostomy. In case of mesenteric thrombosis, resection of the affected part of the small intestine was performed. In case of peritonitis without clear intraoperative detection of perforation of the colon wall, intraoperative lavage was performed. CONCLUSION: Conclusions: 1) The frequency of detection of PMC in patients with COVID-19 in 2020 was 0.62%, and in 2021 - 2.28%. 2) The sensitivity of CT in the diagnosis of surgical complications of PMC was 72%, and the specificity was 58%. 3) Conservative treatment was effective in patients with PMC in 88.8% of cases, 21.2% had complications that required emergency surgical interventions. 4) The total mortality in patients with PMC was 11.36%, although this indicator was significantly higher in the event of surgical complications and operative treatment (22.4%).

Validity of 16 AHRQ Patient Safety Indicators to identify in-hospital complications: a medical record review across nine Swiss hospitals.

The validity of the Agency for Healthcare Research and Quality's Patient Safety Indicators (PSIs) has been established in the USA and Canada. However, these indicators are also used for hospital benchmarking and cross-country comparisons in other nations with different health-care settings and coding systems as well as missing present on admission (POA) flags in the administrative data. This study sought to comprehensively assess and compare the validity of 16 PSIs in Switzerland, where they have not been previously applied. We performed a medical record review using administrative and electronic medical record data from nine Swiss hospitals. Seven independent reviewers evaluated 1245 cases at various hospitals using retrospective data from the years 2014-18. True positives, false positives, positive predictive values (PPVs), and reasons for misclassification were compared across all investigated PSIs, and the documentation quality of the PSIs was examined. PSIs 6 (iatrogenic pneumothorax), 10 (postoperative acute kidney injury), 11 (postoperative respiratory failure), 13 (postoperative sepsis), 14 (wound dehiscence), 17 (birth trauma), and 18 and 19 (obstetric trauma with or without instrument) showed high PPVs (range: 90-99%) and were not strongly influenced by missing POA information. In contrast, PSIs 3 (pressure ulcer), 5 (retained surgical item), 7 (central venous catheter-related bloodstream infection), 8 (fall with hip fracture), and 15 (accidental puncture/laceration) showed low PPVs (range: 18-49%). In the case of PSIs 3, 8, and 12 (perioperative embolism/thrombosis), the low PPVs were largely due to the lack of POA information. Additionally, it was found that the documentation of PSI 3 in discharge letters could be improved. We found large differences in validity across the 16 PSIs in Switzerland. These results can guide policymakers in Switzerland and comparable health-care systems in selecting and prioritizing suitable PSIs for quality initiatives. Furthermore, the national introduction of a POA flag would allow for the inclusion of additional PSIs in quality monitoring.

[Early detection of lung cancer - current status and implementation scenarios]. / Lungenkrebsfrüherkennung ­ derzeitiger Stand und Implementationsszenarien.

The prognosis of conventionally diagnosed lung cancer patients is still rather poor. Two large, randomized trials using screening by low dose CT could demonstrate that early detection in persons with smoking as risk factor can improve this prognosis. Early detection of lung cancer can be achieved by structured screening programs using low dose CT for persons at increased risk, but in addition also by consequent management of incidental pulmonary nodules, which are seen on imaging for other reasons. Integral part of these programs should be prevention measures, especially a consequent, repeated, low-threshold offer of a service for smoking cessation. Programs for lung cancer screening for persons at increased risk are only beneficial for the screenees and cost-effective, if the various parts of the program are optimally integrated and coordinated and all necessary disciplines (especially respiratory medicine, radiology, pathology, thoracic surgery, radiotherapy) are included in a multidisciplinary manner. For Germany the certified lung cancer centres in structured cooperation with physicians in private practice (respiratory physicians, radiologists, general practitioners) would be a good option. It is essential that there is a good perception for the need of early detection of lung cancer in politics and the public and that the persons at risk are reached, contacted and motivated by various methods.

[Prevention, Diagnosis, Therapy, and Follow-up of Lung Cancer - Interdisciplinary Guideline of the German Respiratory Society and the German Cancer Society - Abridged Version]. / Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms.

The current S3 Lung Cancer Guidelines are edited with fundamental changes to the previous edition based on the dynamic influx of information to this field:The recommendations include de novo a mandatory case presentation for all patients with lung cancer in a multidisciplinary tumor board before initiation of treatment, furthermore CT-Screening for asymptomatic patients at risk (after federal approval), recommendations for incidental lung nodule management , molecular testing of all NSCLC independent of subtypes, EGFR-mutations in resectable early stage lung cancer in relapsed or recurrent disease, adjuvant TKI-therapy in the presence of common EGFR-mutations, adjuvant consolidation treatment with checkpoint inhibitors in resected lung cancer with PD-L1 ≥ 50%, obligatory evaluation of PD-L1-status, consolidation treatment with checkpoint inhibition after radiochemotherapy in patients with PD-L1-pos. tumor, adjuvant consolidation treatment with checkpoint inhibition in patients withPD-L1 ≥ 50% stage IIIA and treatment options in PD-L1 ≥ 50% tumors independent of PD-L1status and targeted therapy and treatment option immune chemotherapy in first line SCLC patients.Based on the current dynamic status of information in this field and the turnaround time required to implement new options, a transformation to a "living guideline" was proposed.

HYPERACTIVE BLADDER SYNDROME SECONDARY TO BAROTRAUMA AND CHRONIC STRESS.

OBJECTIVE: The aim: To improve the results of treatment of hyperactive bladder syndrome in men of working age on the background of barotrauma and stress, as a consequence of combat trauma. PATIENTS AND METHODS: Materials and methods: An analysis of the questionnaire and the results of the clinical examination of 32 patients, injured servicemen and people who were injured in combat zones was carried out. The drug solifenacin succinate was used in the treatment complex, which is a specific antagonist of M3 subtype cholinergic receptors. Its influence allows you to achieve relaxation of the bladder detrusor and reduce the contractility of hyperactive bladder. RESULTS: Results: The main criterion for the effectiveness of the treatment was a decrease in the number of urgent cases, the frequency of urination and manifestations of nocturia by 50% or more, which was considered a positive effect. At the same time, the positive effect was differentiated as follows : an improvement of these parameters by 75% or more from the initial value which is a good result; reduction of symptoms in the range of 50-75% is satisfactory; less than 50% is an unsatisfactory result. A positive effect from the treatment after 8 weeks was observed in 88% of patients, of which 52% had a good result and 36% had a satisfactory result. CONCLUSION: Conclusions: The proposed complex of treatment of hyperactive bladder syndrome as a result of combat trauma against the background of barotrauma with neurological consequences and chronic stress allows to achieve a pronounced clinical effect in the vast majority of male patients of working age. And the diagnostic complex allows you to emphasize aspects of clinical vigilance, both for doctors of a specialized branch and of doctors of a general direction.

EARLY DIAGNOSIS OF ASYMPTOMIC CHRONIC ISCHEMIA OF THE LOWER EXTREMITIES.

OBJECTIVE: The aim: To assess the possibility of using a questionnaire and determining the Ankle Brachial Index(ABI) for early diagnosis of asymptomatic ischemia of the lower extremities in patients with various somatic diseases. PATIENTS AND METHODS: Materials and methods: The study involved 294 patients who were receiving inpatient treatment at Communal Non-Profit Enterprise «Uzhgorod Central City Clinical Hospital¼,Communal Non-Profit Enterprise «Transcarpathian Regional Clinical Hospital¼ and Communal Non-Profit Enterprise «Uzhgorod District Clinical Hospital¼. The study was conducted in 36 patients of pulmonological, 52 - neurological, 22 - endocrinological, 28 - rheumatological, 67 - general therapeutic and 89 - surgical patients. In order to detect hidden ischemia, the patients were surveyed according to the Edinburg questionnaire, regional systolic pressure was measured on the tibial arteries of the lower extremities and calculation of the Bone-humerus index (ABI)at rest and after physical exertion (walking), also non-contact skin temperature was measured on the lower leg and thigh. RESULTS: Results: During the study, (ABI) less than 0.9 was found in 108 (36.7%) patients, while in 47 (43.5%) cases, (ABI) decreased only after exercise.In the majority of cases, 98 (90.7%) a decrease in (ABI) was observed on one lower limb. A decrease in the skin temperature of the lower extremities was observed in 141 (48%) patients, 134 (95.1%) of which were diagnosed with diabetes.Symptoms of hidden ischemia, according to the questionnaire, were found in 99 (33.7%) patients.Smoking was observed in 61 (56.5%) patients with symptoms of hidden ischemia. CONCLUSION: Conclusions: As a result of our study, it was found that the specificity of the Edinburg questionnaire in detecting the preclinical stage of ischemia of the lower extremities reaches 88.2%, and the sensitivity - 91.6%. The obtained results indicate the expediency of using the questionnaire in the complex of diagnostics of vascular pathology in patients of various profiles. False-negative results of(ABI)in people with diabetes are associated with mediacalcinosis. In such cases, it is necessary to assess the state of blood flow by measuring the pressure on the back of the foot after physical exertion.

Tributary effects on the ecological responses of a regulated river to experimental floods.

Rivers regulated by dams display several ecosystem alterations due to modified flow and sediment regimes. Downstream from a dam, ecosystem degradation occurs because of reduced disturbance, mostly derived from limitations on flow variability and sediment supply. In the last decade, most flow restoration/dam impact mitigation was oriented towards the development of environmental flows. Flow variability (and consequent disturbance) can be reintroduced by releasing artificial high flows (experimental floods). Flow-sediment interactions during experimental floods represent strong ecosystem drivers, influencing nutrient dynamics, and metabolic and functional properties. In river networks, sediment and water inputs from tributaries generate points of discontinuity that can drive major changes in environmental conditions, affecting habitat structure and determining functional differences between upstream and downstream. However, despite the relevance for management, flow/sediment relations during environmental flows - and more importantly during experimental floods - remain poorly understood, mostly due to the lack of empirical evidence. In this study, we examined how a major tributary (source of water and sediments) modified the physical habitat template of a regulated river, thereby influencing ecological and geomorphological responses to experimental floods. Methods combined high-resolution drone mapping techniques with a wide range of biological samples collected in field surveys before, during, and after experimental floods in an alpine river. Data were used to quantify changes in relevant functional and structural ecosystem properties, relating ecological responses to geomorphological dynamics. Results highlight the importance of tributaries in restoring ecosystem properties lost after damming, enhancing the resilience of the system. In addition, we observed that disturbance legacy played a fundamental role in determining ecological conditions of a river prior to experimental floods, thus confirming that considering flow variability and sediment availability is crucial in adaptive dam management and environmental flows design.

EXPERIENCE OF THE TREATMENT OF PATIENTS WITH ACUTE PANCREATITIS.

OBJECTIVE: The aim: To improve the results of treatment of patients diagnosed with acute pancreatitis. PATIENTS AND METHODS: Materials and methods: The materials of the work are based on the clinical examination and treatment of 301 patients with acute pancreatitis, in the treatment of which, along with classical treatment, a therapeutic and diagnostic complex was used, which allows predicting and preventing the development of abdominal compartment syndrome (ACS). RESULTS: Results: Managed to reduce the number of cases of infected pancreatic necrosis, effectively predict and prevent the development of abdominal compartment syndrome (ACS), reduce the average length of stay of patients in the hospital. CONCLUSION: Conclusions: The use of the proposed management algorithm for patients with acute pancreatitis allows to shorten the treatment period by effectively predicting and preventing the development of pancreatic necrosis, its septic complications and abdominal compartment syndrome.

"Over-preoccupation with healthy food is perceived as worship of the body": Food, culture and beliefs in Ultra-Orthodox Jewish families.

BACKGROUND: Eating behaviours vary by culture and religion, and an understanding of attitudes and practices are essential for providing culturally competent nutritional guidance. The Ultra-orthodox Jewish community is characterized by poor diet, high rates of obesity, anemia and diabetes. This study aimed to acquire insights that could influence the promotion of healthier eating in the Ultra-orthodox and other closed religious communities, particularly regarding children's eating habits and the food they consume. METHODS: In depth face-to-face recorded interviews were conducted with 20 information-rich participants: religious leaders, opinion leaders and education/health professionals from Gur and Chabad, two Ultra-orthodox Jewish religious communities in Israel. The focus was on exploring young family eating behaviours and perceived challenges to encouraging healthier nutrition in the community. Interviews were transcribed and thematic analysis employed using grounded theory. RESULTS: Seven themes were identified with findings that had clear implications for the promotion of health at both the community and individual level. These included spiritual aspects of eating, deficits in knowledge and awareness, less relevance of kashrut than previously thought, the centrality of motherhood and family meals, the quality of food in educational institutions, the significance and sensitivity of Sabbath and festive meals and pragmatic considerations. DISCUSSION AND CONCLUSIONS: By illuminating attitudes and behaviors, the study broadens and enhances our understanding of the Ultra-orthodox communities' perspectives on eating behaviours in the family. The findings have the potential to contribute to strengths-based health promotion for children's nutrition. Recommendations regarding culturally competent guidance and implications for other secluded religious communities are discussed.

The vascular occlusion test using multispectral imaging: a validation study : The VASOIMAGE study.

Multispectral imaging (MSI) is a new, non-invasive method to continuously measure oxygenation and microcirculatory perfusion, but has limitedly been validated in healthy volunteers. The present study aimed to validate the potential of multispectral imaging in the detection of microcirculatory perfusion disturbances during a vascular occlusion test (VOT). Two consecutive VOT's were performed on healthy volunteers and tissue oxygenation was measured with MSI and near-infrared spectroscopy (NIRS). Correlations between the rate of desaturation, recovery and the hyperemic area under the curve (AUC) measured by MSI and NIRS were calculated. Fifty-eight volunteers were included. The MSI oxygenation curves showed identifiable components of the VOT, including a desaturation and recovery slope and hyperemic area under the curve, similar to those measured with NIRS. The correlation between the rate of desaturation measured by MSI and NIRS was moderate: r = 0.42 (p = 0.001) for the first and r = 0.41 (p = 0.002) for the second test. Our results suggest that non-contact multispectral imaging is able to measure changes in regional oxygenation and deoxygenation during a vascular occlusion test in healthy volunteers. When compared to measurements with NIRS, correlation of results was moderate to weak, most likely reflecting differences in physiology of the regions of interest and measurement technique.

EXPERIENCE USING LASER IN THE TREATMENT OF POLYPES OF THE EXTERNAL URETHRAL ORIFICE.

OBJECTIVE: The aim: To improve the results of treatment of patients with polyps of the external urethral orifice by using minimally invasive surgery. PATIENTS AND METHODS: Materials and methods: The materials of the work are based on clinical examination and treatment of 22 patients with polyps of the external urethral orifice in the treatment of which, along with classical treatment were used minimally invasive methods of removal of polyps of the external urethral orifice using high-intensity laser. RESULTS: Results: We managed to reduce the duration of surgery and treatment twice less, to avoid typical complications, which accelerated the regeneration process and the rehabilitation period. CONCLUSION: Conclusions: The use of minimally invasive surgical methods to remove urethral polyps can reduce the duration of treatment by reduction of the thermal and mechanical load on the surrounding tissues and reducing the time of surgery.

Positive transformation towards the Fourth Industrial Revolution: empirical evidence from a technology company.

This article explores the question of how organizations can transform constructively and positively towards the Fourth Industrial Revolution (4IR). It presents insights into the state of the art on 4IR, positive psychology movements PP1.0 and PP2.0 and particularly on German organizations in the 4IR within the South African context. The study uses a qualitative research approach and presents findings from a study conducted with 16 managers across top, middle and lower management levels in a German engineering organization, based in South Africa, operating in Southern Africa. Findings, discussion, conclusions and recommendations provide insights into emerging themes on the 4IR from perspectives that take the context of discourses on the 4IR in developed and developing countries into account. Findings show the importance of five main themes when transforming into the 4IR: (1) Employee management; (2) Innovative technological and systemic change; (3) Work organization; (4) Environment and (5) Network and cooperation. Human communication and connectivity and a balanced human-machine interaction seem to build the core framework for constructive socio-technological change and a meaningful work environment. Thereby, a focus on the positive transformation requires working through the challenges and dark sides of the 4IR as well as a contextual and culture-specific approach to finally create a meaningful, healthy and optimal functioning work environment for the employees.

Sense of coherence in systemic family therapy trainees in times of change.

This study aimed at qualitatively exploring the development of a sense of coherence (SOC) among systemic family therapist trainees (FTT) over a 3-year period. It was conducted in a private family therapy training institute in central Germany. The sample consisted of 66 trainees. The components of SOC and their general health played an important role in the development of FTTs throughout the three training years. Findings show that the SOC component of meaningfulness (motivation) was most frequently mentioned and most important to participants' personal and professional development, followed by comprehensibility (understanding of self, others and the context) and finally by manageability (coping with challenges based on personal, social and professional resources). The three SOC components fostered a positive self-care approach in FTTs and improved health and well-being over the 3 years. Visions of FTT at the end of the training show that they aim at personal and professional growth and development in the Fourth Industrial Revolution (4IR).

Enhanced topical cutaneous delivery of indocyanine green after various pretreatment regimens: comparison of fractional CO2 laser, fractional Er:YAG laser, microneedling, and radiofrequency.

Different devices have been used to enhance topical drug delivery. Aim of this study was to compare the efficacy of different skin pretreatment regimens in topical drug delivery. In six ex vivo human abdominal skin samples, test regions were pretreated with fractional CO2 and Er:YAG laser (both 70 and 300 µm ablation depth, density of 5%), microneedling (500 µm needle length), fractional radiofrequency (ablation depth of ± 80-90 µm), and no pretreatment. The fluorescent agent indocyanine green (ICG) was applied. After 3 h, fluorescence intensity was measured at several depths using fluorescence photography. Significantly higher surface fluorescence intensities were found for pretreatment with fractional Er:YAG and CO2 laser and for microneedling vs. no pretreatment (p < 0.05), but not for radiofrequency vs. no pretreatment (p = 0.173). Fluorescence intensity was highest for the Er:YAG laser with 300 µm ablation depth (mean 38.89 arbitrary units; AU), followed by microneedling (33.02 AU) and CO2 laser with 300 µm ablation depth (26.25 AU). Pretreatment with both lasers with 300 µm ablation depth gave higher fluorescence intensity than with 70 µm ablation depth (Er:YAG laser, 21.65; CO2 laser, 18.50 AU). Mean fluorescence intensity for radiofrequency was 15.27 AU. Results were comparable at 200 and 400 µm depth in the skin. Pretreatment of the skin with fractional CO2 laser, fractional Er:YAG laser, and microneedling is effective for topical ICG delivery, while fractional radiofrequency is not. Deeper laser ablation results in improved ICG delivery. These findings may be relevant for the delivery of other drugs with comparable molecular properties.

Use of technomolecular silver preparations in complex treatment of infected wounds.

OBJECTIVE: The aim: To improve the results of treatment of infected wounds. PATIENTS AND METHODS: Materials and methods:The clinical material is based on clinical observation and treatment of 29 patients with in fected wounds, whose treatment included combination drugs of local action on the basis of techno-molecular silver (in particular «Cadefort-Spray¼), by application to the wound surface. RESULTS: Results: Wound microbial factor, dynamics of wound process, indicators of immune status were evaluated: localadaptive immunity, atopic reactions. CONCLUSION: Conclusions: High efficiency of treatment was observed regardless of the phase of the wound process, which allowed to accelerate wound repair and stimulate the processes of regeneration, strengthen local adaptive immunity, prevent atopic reactions.

Gender-Affirming Hormone Treatment Induces Facial Feminization in Transwomen and Masculinization in Transmen: Quantification by 3D Scanning and Patient-Reported Outcome Measures.

INTRODUCTION: Hormone treatment induces feminization of the body in transwomen and masculinization in transmen. However, the effect of hormone treatment on facial characteristics is still unknown. AIM: We aimed to study whether hormone treatment induces facial feminization and masculinization and how this potential change affects satisfaction and self-esteem. METHODS: In this single-center cohort study, we included 27 transwomen and 15 transmen who received standardized hormone treatment in the Center of Expertise on Gender Dysphoria, VU University Medical Center Amsterdam. Facial 3-dimensional images were obtained at baseline and at 3 and 12 months. At each image, 22 facial landmarks were placed. Furthermore, the FACE-Q Satisfaction with Facial Appearance Overall and the Rosenberg self-esteem scale were obtained at the same measurement points. MAIN OUTCOME MEASURES: The main outcome measures included the relative local shift of skin in millimeters in the 22 landmarks in the transverse (x-axis), coronal (y-axis), and sagittal (z-axis) anatomic axes, the color maps, and the outcomes of the questionnaires. RESULTS: After 12 months, cheek tissue in transwomen increased, with 0.50 mm (95% CI 0.04-0.96) in the x-axis and 1.08 mm (95% CI 0.31-1.85) in the z-axis. Tissue in the jaws decreased with -0.60 mm (95% CI -1.28-0.08) in the x-axis and -0.18 mm (95% CI -0.03-0.33) in the y-axis. Cheek tissue in transmen decreased with -0.45 mm (95% CI -1.00-0.11) in the x-axis and -0.84 mm (95% CI -1.92-0.25) in the z-axis. These changes already started after 3 months. An increase in satisfaction with the facial appearance was found in both transwomen and transmen. There were no changes in reported self-esteem. CLINICAL IMPLICATION: These results could lead to more realistic expectations of facial changes. Furthermore, our results suggest that the face continues to change for at least a year, which could suggest that performing facial feminization surgery after 1 year of hormone treatment might be too early. STRENGTH & LIMITATIONS: This study is the first that provides insight into the facial changes in transgender individuals receiving hormone treatment, and it introduces an objective method to examine (small) facial changes. Our study is limited by the poor reliability of the landmarks, the difficulty of facial fixation, and the lack of gender-specific questions in the questionnaires. CONCLUSIONS: Hormone treatment in transwomen induces an increase in cheek tissue and a decrease in jaw tissue. In transmen a tendency of decrease in cheek tissue and an increase in jaw tissue was found. These changes are in the direction of the desired gender. Tebbens M, Nota NM, Liberton NPTJ, et al. Gender-Affirming Hormone Treatment Induces Facial Feminization in Transwomen and Masculinization in Transmen: Quantification by 3D Scanning and Patient-Reported Outcome Measures. J Sex Med 2019;16:746-754.

Defining aggressive or early progressing nononcogene-addicted non-small-cell lung cancer: a separate disease entity?

A substantial proportion of patients with nononcogene-addicted non-small-cell lung cancer (NSCLC) has 'aggressive disease', as reflected in short time to progression or lack of disease control with initial platinum-based chemotherapy. Recently, clinical correlates of aggressive disease behavior during first-line therapy have been shown to predict greater benefit from addition of nintedanib to second-line docetaxel in adenocarcinoma NSCLC. Positive predictive effects of aggressive disease have since been reported with other anti-angiogenic agents (ramucirumab and bevacizumab), while such features may negatively impact on outcomes with nivolumab in nonsquamous NSCLC with low PD-L1 expression. Based on a review of the clinical data, we recommend aggressive nonsquamous NSCLC should be defined by progression within <6-9 months of first-line treatment initiation.