Combined Treatment Of Patients Research Articles

A Multi-Center, Prospective, Observational Study to Evaluate the Therapeutic Effectiveness and Safety of an Olmesartan/Amlodipine Plus Rosuvastatin Combination Treatment in Patients with Concomitant Hypertension and Dyslipidemia.

Introduction: This study assessed the therapeutic effectiveness of a single-pill combination (SPC) of olmesartan/amlodipine plus rosuvastatin for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) in patients with hypertension and dyslipidemia. Methods: Adult patients with hypertension and dyslipidemia who were decided to be treated with the study drug were eligible. The primary endpoint was the proportion of patients who achieved BP, LDL-C and both BP and LDL-C treatment goals at weeks 24-48. Secondary endpoints were assessed at weeks 24-48 and included changes in BP and LDL-C levels from baseline; the proportion of patients who achieved treatment goals who were initially classified as uncontrolled at baseline; changes and percent changes in lipid parameters; changes in both BP and LDL-C levels among patients who reached treatment goals who were followed for more than 24 weeks; and the overall safety profile. Results: A total of 5476 patients were enrolled, and 4411 patients comprised the effectiveness evaluation set. The proportions of patients who reached the treatment goals for BP, LDL-C levels, and both BP and LDL-C levels were 67.93% [95% confidence interval (CI) 66.52-69.32], 80.19% [95% CI 78.85-81.49], and 58.07% [95% CI 56.43-59.7], respectively. Secondary endpoints showed statistically significant changes. Overall, the treatment was well tolerated. Conclusions: The treatment of patients with hypertension and dyslipidemia with the olmesartan/amlodipine plus rosuvastatin SPC was associated with significant decreases in SBP/DBP and LDL-C levels, and a high proportion of patients achieved the BP and LDL-C treatment goals. The finding of this study is worthwhile in that this study evaluated the effectiveness and safety in a broad patient population representative of those seen in everyday clinical practice.

Combination treatment for patients with benign prostatic hyperplasia

The Manual presents the possibilities of using the MAVIT device in the combination treatment of patients with benign prostatic hyperplasia. The content of the Manual is consistent with the higher education program for training the highest qualification resident physicians and the professional retraining program for physicians (OD.A.03.2.3 Alternating Currents, Electric, Electromagnetic and Magnetic Fields. High, Ultra-High and Extra-High Frequency) in the specialty 31.08.50 “Physiotherapy” and (B.1.B.1.4.5.1 “Physiotherapy in Urology,” B.1.B.1.6.3.5. “Prostatitis”) in the specialty 08/31/68 “Urology”. The team of authors has, based on the available scientific data and their own clinical observations, summarized the information relative to the use of the MAVIT device in the combination treatment of patients with benign prostatic hyperplasia and outlined its indications and contraindications. The equipments used in performing the procedures are characterized. This Manual was developed and prepared by the workers of the Chair of Urology with Course of Surgical Diseases of the I. P. Pavlov Ryazan State Medical University jointly with the workers of the chairs of urology, surgical andrology, physical therapy, sports medicine and medical rehabilitation, and the workers of the Research Institute of Molecular and Personalized Therapy of the Federal State Budgetary Educational Institution of Further Professional Education Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia in accordance with the system of standards for information, library and publishing. ICD-10 code: Chapter XXI. Factors influencing health status and contact with health services.

Efficacy of combination treatment in a patient with temporomandibular joint dysfunction

Background: Muscle and joint dysfunction is a common complication, particularly in females over 40 years. It is strongly associated with age-related hormonal changes in the bones, as well as concomitant dentoalveolar deformities and tooth loss. Case description: The efficacy of combination treatment of dentoalveolar abnormalities and deformities complicated by temporomandibular joint (TMJ) dysfunction was demonstrated. The efficacy of combination treatment in patients with missing teeth, as well as dentoalveolar abnormalities and deformities complicated by TMJ dysfunction, was confirmed. To ensure a representative before-and-after comparison, the restoration of masticatory efficiency following orthodontic and orthopedic rehabilitation was assessed. A physical examination in patient M. revealed hypertonia of masticatory muscles, restricted mouth opening, jaw shifting to the left, partially absent dentition in distal sections, and prosthetic restoration failure. On MRI, there were signs of deforming arthrosis of both TMJs. The following observation methods were used to assess the efficacy of rehabilitation: questioning to identify symptoms of TMJ pain; follow-up examination for joint clicking when opening the mouth; palpation of the external pterygoid muscle, masticatory muscle, and internal pterygoid muscle; X-ray examination (TMJ CT and MRI) following treatment; masticatory efficiency assessment using a masticatory performance test (according to Trezubov) before and after treatment. Diagnostic testing following combination orthodontic and orthopedic treatment revealed that the patient’s left TMJ no longer felt heavy, and she could open her mouth easily; moreover, jaw shifting resolved, and masticatory muscle rigidity decreased. Conclusion: This clinical case demonstrates why orthopedic surgeons and orthodontists must collaborate in the diagnosis and treatment of TMJ dysfunction. The authors present a well-established approach to the treatment of patients with TMJ dysfunction that has been used successfully in clinical practice for several years.

Study of anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats

Introduction: The combination treatment of patients with dentition problems including endodontic-periodontal lesions (EPL) is known to widely involve anti-inflammatory drugs, including non-steroidal anti-inflammatory agents, and antimicrobial drugs, in particular antibiotics and antiseptics, from which the former often lead to the development of gastro- and neuropathy, lesions of kidneys and liver, as well as the cardiovascular system, and the latter, in addition to serious side effects, lead to the development of steady resistance of pathogenic microorganisms and dysbacteriosis. This necessitates search for and development of new molecules with a wide range of therapeutic effects aimed to block the infectious and inflammatory process and to restore the functional ability of teeth in EPLs as much as possible (depending on a lesion severity). The aim of the study was to examine the anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats. Materials and Methods: EPL simulation in experiments on the anesthetized rats was conducted in the following way: first, the pulp cavity of lower incisors was opened and left exposed to infection; then periodontal inflammation was induced using a ligature. Thirty days later, EPL developed in the animals. An N-isopropenylimidazole zinc metal complex derivative (laboratory code Pilim-1, prepared in form of gel), reference drug Metrogyl Denta® (M-D, dental gel), as well as the combination Pilim-1 + M-D were applied daily for 14 days on the lower incisors and appropriate gums, and also placed in the gingival pockets and pulp cavities, with pulp partially removed beforehands. After euthanasia of the animals on the 15th day of the experiments, gingival homogenates were assayed for the activity of elastase, urease, catalase, the level of malondialdehyde, and the antioxidant-prooxidant index was calculated, while pulp homogenates were assayed for the activity of elastase, urease, alkaline and acidic phosphatases, and the mineralizing index was calculated. Results and Discussion: In the gum in EPL, Pilim-1 and, especially, the combination Pilim-1+M-D more significantly than M-D have a pronounced anti-inflammatory, antioxidant and antimicrobial (reduce a microbial content level) effects. In the pulp in EPL, Pilim-1 and, to a greater extent, the combination Pilim-1 + M-D in a more pronounced way than M-D have anti-inflammatory, antimicrobial (reduce a microbial content level) and mineralizing effects. In the therapeutic action mechanisms of Pilim-1 and, especially, the combination Pilim-1 + M-D in EPL conditions, their ability to have an antihypoxic effect and an inhibitory effect on cyclooxygenase and 5-lipoxygenase is likely to play a very important role, in addition to their identified effect on the examined metabolic processes. Besides, a certain role may be played by the presence of zinc and imidazole in the structure of Pilim-1, as they have a wide range of biological activity. Conclusion: The presented results of studying Pilim-1 and its combination with M-D indicate their high therapeutic efficiency, especially when using the latter in the experimental EPL in rats, which makes it possible to consider Pilim-1 and Pilim-1 + M-D as potential therapeutic agents to treat EPL.

Comparison of the efficacy of neoadjuvant chemotherapy with FLOT regimen and adjuvant chemotherapy with XELOX/FOLFOX regimen in patients with locally advanced gastric cancer: A retrospective study

Background. To date, there is no consensus on the preferred sequence of combined treatment in patients with locally advanced gastric cancer (perioperative chemotherapy – POCT or primary surgical treatment). No direct comparison of these approaches had been conducted before. Aim. To compare, in retrospective analysis, 3-year relapse-free (RFS) and overall survival (OS) in patients receiving POCT FLOT or adjuvant chemotherapy XELOX/FOLFOX for locally advanced gastric cancer. Materials and methods. The assessment included 153 patients who underwent POCT FLOT and 171 patients who underwent surgical treatment at the first stage. When evaluating the initial characteristics, it was shown that patients with ECOG (The Eastern Cooperative Oncology Group) stage 1-2, clinical stage cT4a-b, cN2-3 and Bormann type 4 to were significantly more common in the POCT group. Morphological characteristics: grade, presence of signet cell carcinoma, HER2/neu overexpression, microsatellite instability, sensitivity to immunotherapy (Combined Positive Score) didn't differ. Results. With a median follow-up of 40 months, it was shown that the long-term results assessed in all included patients were better in the group with primary surgical treatment: 3-year RFS was 55 and 40% (risk ratio – RR 1.33, 95% confidence interval – CI 1.08–1.64; р=0.007). 3-year OS was 68 and 56% (RR 1.36, 95% CI 1.02–1.8; р=0.04), respectively. However, when evaluating patients who received surgical treatment in the POCT group (n=121, 79%), the results did not differ: 3-year RFS 55 and 50% (RR 0.9, 95% CI 0.71–1.16; р=0.97), 3-year OS 68 and 63% (RR 1.1, 95% CI 0.84–1.59; р=0.97). Insufficient volume of adjuvant chemotherapy (75% of the dose) significantly worsened long-term results (3-year OS 43 and 71%; p=0.002). Conclusion. The obtained data of a retrospective analysis did not reveal the advantages of any of the approaches provided that the surgical stage was performed in patients receiving POCT. To obtain more objective results, it is necessary to conduct randomized multicenter studies in the high volume centers, providing the necessary sample capacity, quality of diagnosis and treatment. Thus, the design of future studies should be based on the hypothesis of non-inferiority, which inevitably entails a significant increase in the required number of observations to obtain reliable sampling power.

OA14.06 Divarasib Single-Agent Long-Term Follow-up and Atezolizumab Combination Treatment in Patients with KRAS G12C-Positive NSCLC

OA14.06 Divarasib Single-Agent Long-Term Follow-up and Atezolizumab Combination Treatment in Patients with KRAS G12C-Positive NSCLC

Immune escape between endoplasmic reticulum stress-related cancer cells and exhausted CD8+T cells leads to neoadjuvant chemotherapy resistance in ovarian cancer

Our study aims to explore the effects of neoadjuvant chemotherapy (NACT) on tumour cells and immune cells in the immune microenvironment of patients with high-grade serous ovarian cancer (HGSOC).Single-cell RNA sequencing data of paired ovarian cancer tissues were analysed before and after NACT in 11 patients with HGSOC. The effect of NACT on two major cell components of the tumour microenvironment, epithelial cells and CD8+T cells, was investigated. The mechanisms of epithelial cell evasion by NACT and immune killing were explored from the perspectives of gene expression, functional characteristics, transcriptional regulation, and cell communication. Key targets for reversing NACT resistance were identified and possible therapeutic strategies proposed.While NACT improved the de novo differentiation of anti-tumour CD8+T cells, enhancing their anti-tumour function, it increased the proportion of cancer cells with high HSP90B1 expression. Thus, the potential reasons for NACT resistance were identified as: 1) high levels of endoplasmic reticulum stress (ERS) characteristics, 2) high expression of the MDK-NCL ligand-receptor pair between them and exhausted CD8+T cells before NACT, and 3) high expression of the NECTIN2-TIGIT immune ligand-receptor pair between them and exhausted CD8+T cells after NACT.Thus, our study reveals the mechanisms underlying NACT resistance in patients with HGSOC from the perspective of the independent and interactive roles of cancer cells and CD8+T cells. We propose therapeutic strategies targeting the ERS marker HSP90B1 and the immune escape marker MDK before or during NACT, while targeting NECTIN2 blockade after NACT. This approach may offer new insights into combination treatments for patients with HGSOC displaying NACT resistance.

Long-Term Vonoprazan and Acotiamide-Refractory Patients With Functional Dyspepsia Partly Exhibit Pancreatic Enzyme Abnormalities.

Although a new potassium-competitive acid blocker (P-CAB)vonoprazan has been developed in Japan, no data are available regarding long-term vonoprazan or vonoprazan and acotiamide combination treatment in patients with functional dyspepsia (FD). A total of 73 consecutive patients with FD diagnosed according to the Rome III classification were enrolled. Forty-two patients with FD were treated with vonoprazan monotherapy and thirty-one patients with FD were treated with vonoprazan and acotiamide combination therapy for 24 weeks. The levels of five pancreatic enzymes were measured, and the overall treatment efficacy (OTE) was defined as the ratio of FD patients with improved or unchanged in all items of GSRS and FD symptom scores after the treatment. Treatment with vonoprazan monotherapy and vonoprazan and acotiamide combination therapy significantly improved FD symptoms. There were no significant differences in OTE between patients treated with vonoprazan monotherapy (42.9%) and those treated with vonoprazan and acotiamide combination therapy (52%). There were no significant differences in duodenal eosinophilic infiltration between the improved and unimproved groups treated with vonoprazan alone and vonoprazan and acotiamide combination therapy, respectively. In contrast, there was a significant difference (P = 0.004) in the ratio of pancreatic enzyme abnormalities between the improved and unimproved patients treated with vonoprazan monotherapy and those treated with vonoprazan and acotiamide combination therapy. Long-term vonoprazan alone or vonoprazan and acotiamide combination therapy significantly improved each FD symptom. The OTE in patients treated with vonoprazan alone or vonoprazan and acotiamide combination therapy was only 50%. Long-term vonoprazan and acotiamide combination therapy may differentiate patients with pancreatic enzyme abnormalities from those with FD.

Efficacy and Safety of Low-Dose Bisoprolol/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Systematic Review and Meta-Analysis.

Objectives: This systematic review and meta-analysis aimed to assess the blood pressure (BP)-lowering effect and the safety profile of low-dose bisoprolol/hydrochlorothiazide combination treatment in patients with hypertension. Methods: Multiple electronic databases were systematically searched, and five clinical studies were included in the meta-analysis. Results: Treatment with bisoprolol/hydrochlorothiazide significantly reduced systolic BP (SBP) [mean difference (MD): -8.35 mmHg, 95% confidence interval (CI): -11.44, -5.25 mmHg versus control; MD: -9.88 mmHg, 95%CI: -12.62, -7.14 mmHg versus placebo] and diastolic BP (DBP) [MD: -7.62 mmHg, 95%CI: -11.20, -4.04 mmHg, versus control; MD: -8.79 mmHg, 95%CI: -11.92, -5.67 mmHg versus placebo]. Moreover, BP response rate and BP control rate after low-dose bisoprolol/hydrochlorothiazide combination treatment were significantly greater compared to control [odd ratio (OR) for response rate: 4.86, 95%CI: 2.52, 9.37; OR for control rate: 1.67, 95%CI: 1.11, 2.51]. Finally, treatment with low-dose bisoprolol/hydrochlorothiazide was associated with a reduced risk of any adverse event (AE) and peripheral edema compared to control. Conclusions: Overall, our results reaffirm the safety and efficiency of prescribing bisoprolol/hydrochlorothiazide combination treatment in stage I and II hypertension.

Immune checkpoint inhibitors and radiotherapy in gastrointestinal cancer treatment

Background. In recent decades, immunotherapy has become a topical area of research in the complex treatment of oncological diseases. A significant achievement in the immunotherapy of oncological diseases was the discovery of immune checkpoint proteins, which are effective inhibitors of the immune response. Immune checkpoint inhibitors (ICIs) have been approved for the treatment of certain gastrointestinal malignancies. However, the clinical efficacy of ICIs monotherapy remains low. To improve the outcome of treatment, numerous studies are conducted in which immunotherapy is combined with other standard methods of anticancer treatment. Radiation therapy (RT) may enhance the antitumor immune response when combined with ICIs and is worth considering when combined with immunotherapy. The effectiveness of the combined strategy is actively being investigated in clinical trials. Purpose – to highlight the latest achievements in the field of combined use of immunotherapy with ICIs and RT in malignant neoplasms of the gastrointestinal tract. Materials and methods. Data searches for the review were conducted using PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases. The data of works published in 2013-2023 were analyzed and systematized. Results and discussion. The rationality of the combination of RT and immunotherapy was substantiated. The results of the combined use of neoadjuvant chemoradiotherapy (CRT) and immunotherapy with ICIs in patients with resectable esophageal cancer and combined treatment in patients with advanced disease are analyzed. The clinical results of the use of ICIs in combination with RT or CRT in patients with gastric cancer and the combination of ICIs and RT in patients with hepatocellular carcinoma are presented. The clinical effects of adding ICIs to neoadjuvant RT or CRT in patients with locally advanced and borderline resectable pancreatic cancer and the results of trials of a combined strategy in patients with advanced disease are characterized. The clinical efficacy of the combined approach in locally advanced rectal cancer, which is a routine area of RT application, and in metastatic disease is reviewed. The results of small studies of combined treatment involving patients with metastatic colorectal cancer are presented. Conclusions. Over the past decade, research in the field of immunotherapy for gastrointestinal tumors has increased significantly. Based on the synergistic effects of radiation therapy and immune checkpoint inhibitors, the combination of these therapeutic approaches is increasingly being tested in gastrointestinal cancer to improve treatment outcomes. Published studies have shown encouraging results with satisfactory toxicity. However, most clinical trials are retrospective, non-comparative phase I/II trials and are limited to a small number of patients. The results of these studies can serve as a basis for conducting multicenter prospective studies with large sample sizes to confirm the effectiveness of combined therapy.

The Long-Term Results of Electrochemotherapy in the Treatment of Patients with Locoregionally Advanced, Unresectable Melanoma.

Background/Objectives: Despite observing progress in recent years in the treatment of patients with advanced melanoma, the optimal management of locoregional recurrence has not been determined. Various methods are used to treat this group of patients. One of these methods is electrochemotherapy. The present study presents the distant results in treating patients with the locoregional recurrence of melanoma, using the technique of electrochemotherapy. Methods: This study includes a retrospective analysis of 88 patients' data with locoregional melanoma recurrence, treated with electrochemotherapy (ECT) between 2010 and 2023, in two reference centers. Results: Approximately 80% of patients responded to the ECT treatment, achieving partial or complete remission. In a multivariate analysis, statistically significant longer overall survival was found in the group of patients who achieved complete remission after ECT and were treated with immunotherapy. Discussion: The results may suggest the existence of synergy between ECT and immunotherapy. However, confirmation of this fact requires further prospective studies that will also establish the role of ECT in the combination treatment of patients with locoregional recurrence of melanoma.

Preliminary results from a multi-center phase Ib/II study of RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2 positive locally advanced muscle-invasive urothelial bladder cancer (Hope-03).

e16595 Background: To evaluate the safety and efficacy of RC48-ADC, a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab, a PD-1 antibody, as a novel neoadjuvant treatment combination in patients with HER2 positive locally advanced muscle-invasive bladder cancer (MIBC). The study design has been presented at 2022 ESMO Asia meeting. The preliminary results would be reported this time. Methods: This is a Ib/II, multi-center, open-label, single-arm study (ChiECRCT20210564). 51 patients with pathological and imaging diagnosed cT2-4bN0-3M0-1a HER2 positive MIBC will be included. RC48-ADC is given every 2 weeks with a maximum dose of 120mg intravenously, and tislelizumab is given every three weeks at the dose of 200mg intravenously. Treatment efficacy will be performed by imaging and transurethral resection of tumors after the neoadjuvant treatment. Patients without disease progression will receive radical cystectomy or bladder-sparing therapies based on individual risk profiles and preferences. The primary endpoints are clinical complete remission rate (cCR, T0/Ta/Tis), pathological complete remission rate (pCR) and safety. The secondary endpoints are disease control rate (DCR), overall survival (OS), local recurrence free survival (LRFS), distant metastasis free survival (DMFS) and quality of life. Results: Until now, 18 patients were included successfully, with 3 female patients and 15 male patients. And the median age was 64.47 years old. Of them, 7 patients were HER2(2+), and 11 patients were HER2(3+). The clinical stages were T2-4aN0-3M1a. Sixteen patients had the primary efficacy evaluation by now. After the neoadjuvant treatment, 7 patients were T0, 4 patients Tis, 2 patients partial response (PR), 2 patients stable disease (SD) and 1 patient suffered from progress of local disease. Hence the cCR rate was 68.75%, and the DCR was 90.91%. Fourteen patients chose radiotherapy as bladder-sparing therapy and no evidence of tumor in 6 patients who received treatment efficacy after radiotherapy. Two patients received radical cystectomy and pT3N0M0 was achieved for both. No patient died so far. For safety analysis, 4 patients suffered from immune-related adverse event, namely, grade 2 myositis, grade 1 elevated transaminase and grade 1 hyperthyroidism which led to treatment interruption of tislelizumab. And 10 patients experienced RC48-ADC related toxicities, including grade 1 elevated transaminase, grade 1 erythra and grade 1 paresthesia. No treatment related dose reduction happened. Conclusions: The novel neoadjuvant combination of RC48-ADC and tislelizumab showed promising down stage efficacy in patients with HER2 positive locally advanced MIBC and the toxicities were manageable, which would be verified by the final analysis. Clinical trial information: ChiECRCT20210564.

Assessing the accuracy of postoperative results of virtualplanning of the surgical stage in the combined treatmentof patients with gnathic forms of malocclusion

o improve the methods of preoperative planning of the surgical stage in the combined treatment of patients with jaw abnormalities using 3D technologies with subsequent assessment of the accuracy of the result obtained. Material and methods. The study group included 90 patients with jaw malformations aged from 18 to 45 years. in the period from 2017 to 2021. Comprehensive examination, preoperative virtual planning, and combined treatment of the dentoalveolar abnormalities were performed in 45 female and 45 male patients. The patients were assigned into 3 equal groups of 30 subjects depending on the planning method. The quality of preoperative planning and postoperative results were assessed using 35 cephalometric measurements.Results. According to the results of calculating the absolute magnitude of planned and actual relocations, as well as the deviation of postoperative values from the plan for each of the 35 measurements, inconsistencies were revealed in 20 of 35 coordinates in the FIRST group. The SECOND group showed inconsistencies in only 4 of the 35 measurements. The THIRD group had discrepancies in 7 out of 35 measurements.Conclusion. The development of digital technologies in medicine has generated a wide range of tools to improve the accuracy of surgical planning and visualization of expected changes in the patient. The use of three-dimensional (3D) imaging techniques allows to combine information about the structure of the soft tissues of the face, facial skeleton, and dentition. Computer simulation of operations is becoming an increasingly important tool in the field of maxillofacial surgery, as it provides superior opportunities for preoperative planning and reduction of possible risks at all stages – before, during, and after surgery.Key words: orthognathic surgery, virtual surgical planning, 3D analysis, CAD/CAM surgical splint, 3D-printed surg Цель исследования. Усовершенствование методов предоперационного планирования хирургического этапа комбинированного лечения пациентов с аномалиями челюстей с применением 3D-технологий с по- следующей оценкой точности полученного результата. Материал и методы. В исследуемые группы вошли 90 пациентов с аномалиями развития челюстей в период с 2017 по 2021 г. в возрасте от 18 до 45 лет. Комплексное обследование, предоперационное виртуальное планирование и комбинированное лечение зубочелюстных аномалий провели 45 пациентам женского пола, 45 – мужского. Пациенты были распределены в 3 группы по 30 человек в зависимости от метода планиро- вания. Оценку качества предоперационного планирования и послеоперационных результатов проводили по 35 цефалометрическим координатам. Результаты. По результатам вычисления абсолютного размера планового и фактических перемещений, а также отклонения значений после операции от плана для каждой из 35 координат для первой группы были выявлены несоответствия в 20 из 35 координат. Для второй группы показали несоответствия только в 4 из 35 координат. Для третьей группы выявили несоответствия в 7 из 35 координат Заключение. Развитие цифровых технологий в медицине привело к появлению широкого спектра инструмен- тов, направленных на повышение точности планирования операций и визуализации ожидаемых изменений у пациента. Использование трехмерных (3D) методов визуализации позволяет объединить информацию о структуре мягких тканей лица, лицевого скелета и зубного ряда. Компьютерное моделирование операций становится все более важным инструментом в области челюстно-лицевой хирургии, т.к. это предоставляет улучшенные возможности для предоперационного планирования и снижения возможных рисков на всех этапах – до, во время и после операции.

Therapeutic combination of "keys" to target low-density lipoprotein cholesterol level

This article updates the continuing high prevalence of lipid metabolism disorders and their connection with the development of cardiovascular pathology associated with atherosclerosis. Attention is focused on the existing lack of adherence to the correction of dyslipidemia, both on the part of patients and medical workers, as well as the problem of failure to achieve target levels of low-density lipoprotein cholesterol with standard statin treatment. The evolution of modern therapy for lipid metabolism disorders is shown and the feasibility of early initiation of combination treatment in patients with very high and high cardiovascular risk in the presence of severe dyslipidemia is substantiated, and possible treatment strategies existing in current recommendations are outlined. In the presented work, using the example of an outpatient 54 years old after undergoing stenting of the coronary arteries, who has a very high cardiovascular risk (established diagnoses of coronary heart disease, post-infarction cardiosclerosis, hypertension) with failure to achieve the target level of low-density lipoprotein cholesterol of less than 1.4 mmol/l The therapeutic effectiveness of a double combination – an inhibitor of cholesterol absorption in the intestine – ezetimibe at a dose of 10 mg with a statin at the maximum tolerated dosage was demonstrated. It has been shown that the proposed combined lipid-lowering treatment is clinically and laboratory safe. Arguments in favor of starting combination treatment in this clinical case include not only the failure to achieve the target value of low-density lipoprotein cholesterol on high-intensity statin monotherapy as part of secondary prevention and possible familial hypercholesterolemia, but also a hereditary history of cardiovascular pathology, early onset of cardiovascular diseases in patient.

The use of thromboaspiration and combined treatment in patients with ischemic stroke in real-life clinical practice

The effectiveness of staged reperfusion therapy in real clinical practice requires clarification. Objective: to evaluate the efficacy and safety of mechanical thromboextraction and staged reperfusion therapy with alteplase in real clinical practice. Material and methods. The study included 106 patients who were retrospectively divided into two groups: Group I underwent staged reperfusion therapy (intravenous thrombolysis with alteplase followed by aspiration thromboextraction), Group II underwent thromboaspiration only. The clinical and functional results, incidence of hemorrhagic transformation and mortality rate were compared. Results. The groups did not differ in terms of demographic data, cardiovascular risk factors or stroke severity. Group II patients were characterized by a longer delay in reperfusion therapy (225 minutes versus 180 minutes) and a lower score on the Alberta Stroke Programme Early CT score (ASPECTS; 8.8 points versus 9.3 points). There were no differences in National Institutes of Health Stroke Scale (NIHSS) scores at day 28, dynamics of NIHSS scores, Rankin scores at day 28, rates of hemorrhagic transformation or mortality. In both groups, the deceased patients were older; in Group I they suffered more frequently from atrial fibrillation, in Group II – from diabetes mellitus type 2. In addition, mortality in Group II was associated with a higher severity of early signs of cerebral infarction.Conclusion. The results of the analysis of real-life clinical practice show the comparability of the efficacy and safety of staged reperfusion therapy and isolated thromboaspiration in a “natural” selection of patients.

Benefits of Early Combination Treatment in Patients with Amyotrophic Lateral Sclerosis: A Case Series (P6-11.012)

Benefits of Early Combination Treatment in Patients with Amyotrophic Lateral Sclerosis: A Case Series (P6-11.012)

A Pilot Study of Anlotinib as a Combination Treatment in Advanced Nasopharyngeal Carcinoma.

To investigate the short-term objective response and treatment toxicity of anlotinib as a combination treatment in patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (RM-NPC). Patients with RM-NPC who received anlotinib as a combination treatment between March 2021 and July 2022 were retrospectively analyzed.The efficacy and safety of anlotinib as a combination treatment were analyzed. A total of 17 patients with RM-NPC were included in this study. Of these patients, 2 (11.8%) had local recurrence, 4 (23.5%) had cervical lymph node recurrence, and 11 (64.9%) had distant failure. The most common metastatic site was the liver (47.1%), followed by the lung (23.5%) and bone (23.5%). Anlotinib was given as first-line treatment in 3 patients (17.6%), second lines treatment in 7 patients (41.2%), and third to six-lines treatment in 7 patients (41.2%). All patients received anlotinib combined with chemotherapy and/or immunotherapy. One patient achieved a complete response (5.9%), 7 patients had a partial response (41.2%), 5 patients had stable disease (29.4%), and 4 patients had progressive disease (23.5%). The overall disease control rate and the overall response rate were 76.5% and 47.1%, respectively. The median progression-free survival was 8.1 months, and the median overall survival was not reached. The incidence of grade 3 adverse events was 30%. No unexpected side effects or treatment-related death were observed. Anlotinib, as a combination treatment, has a promising antitumor activity and a manageable safety profile in patients with RM-NPC. Our results add to the growing evidence that supports the benefits of combining antiangiogenic drugs in RM-NPC. Randomized controlled clinical trials investigating the evaluation of anlotinib are warranted.

A survival nomogram model for patients with resectable non-small cell lung cancer and lymph node metastasis (N1 or N2) based on the Surveillance, Epidemiology, and End Results Database and single-center data.

The ability to predict survival in patients with lymph node metastasis has long been elusive. After surgery, the basis for decision-making on the combination treatment of patients is not clear. The purpose of this study was thus to build a survival nomogram model to effectively predict the overall survival (OS) of patients with non-small cell lung cancer (NSCLC) and lymph node metastasis. The number of dissected lymph nodes (NDLN), number of positive lymph nodes (NPLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) were included in this study to determine the risk factors in patients with advanced NSCLC. The data of 5,132 patients with NSCLC and lymph node metastasis (N1 or N2) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database according to inclusion and exclusion criteria and used as the training cohort. We enrolled 117 patients from the First Affiliated Hospital, Zhejiang University School of Medicine as the external validation cohort. Receiver operating characteristic (ROC) analyses were performed to determine the best cutoff values for predicting the prognosis of patients with NSCLC. Based on the risk factors affecting prognosis, a nomogram was constructed using univariate and multivariate Cox proportional hazard regression models. The discrimination ability of the nomogram was evaluated with the concordance index (C-index) and calibration curves. For the independent risk factors, survival curves were drawn using Kaplan-Meier analysis. ROC curve analysis showed that the optimal NPLN cut-off value was 4, LNR was 0.26, and LODDS was -0.25, respectively. However, LNR was nonsignificant in multivariate analysis, with a P value of 0.274. The novel survival nomogram model included seven independent risk factors, among which were NPLN, LODDS, and chemotherapy. Model 4, which included N stage, NPLN, and LODDS, had a higher likelihood ratio (LR) and C-index than did the other models. The C-index was 0.648 [95% confidence interval (CI): 0.636-0.659] in the training cohort and 0.807 (95% CI: 0.751-0.863) in the external validation cohort, showing good prognostic accuracy and discrimination ability. According to the median risk score, the patients in the training cohort and external validation cohort were divided into high-risk and low-risk groups, between which significant differences in OS were found. In the training cohort, age, sex, T stage, N stage, NPLN, LODDS, and chemotherapy were significantly associated with OS (P<0.001). In the external validation cohort, T stage, NPLN, LODDS, and chemotherapy were found to be correlated with OS. The NPLN and LODDS nomogram is an accurate survival prediction tool for patients with N1 or N2 NSCLC. Patients with lymph node metastasis can benefit from chemotherapy, but no evidence shows that radiotherapy is necessary for patients with resectable NSCLC.

Clinical efficacy of intense pulsed light combined with low-dose intralesional corticosteroids in treating noninfectious granulomas after mesotherapy: A case series analysis.

Mesotherapy is a popular cosmetic procedure for localized delivery of substances. However, due to the lack of standardized processes, there are potential risks of adverse reactions. Granulomas formation is one of the chronic reactions which impose significant physical and mental burdens on patients. The aim of this analysis is to evaluate the safety and feasibility of combining intense pulsed light (IPL) with intralesional corticosteroids for treating noninfectious granulomas after mesotherapy. This retrospective observational case series included patients who suffer from noninfectious granulomas after mesotherapy and received combination of IPL and intralesional corticosteroids treatment between October 2021 and December 2022 at Peking University Shenzhen Hospital, Shenzhen, China. The process and effect were analyzed and summarized. Among the seven patients, five expressed extreme satisfaction with the efficacy, while two was slightly satisfied. The physicians believed that all patients had shown significant improvement. No adverse reactions or recurrences were observed during follow-up. Based on this analysis, the application of the combined treatment in patients suffering from noninfectious granuloma due to mesotherapy demonstrates good clinical efficacy and safety, making it worth considering as a treatment option.

Colistin monotherapy or combination for the treatment of bloodstream infection caused by Klebsiella pneumoniae: a systematic review and meta-analysis.

Bloodstream infection of Klebsiella pneumoniae (BSI-KP) were associated with increased mortality. Klebsiella pneumoniae was tested to susceptible to colistin by E-test and broth microdilution method in clinical laboratory. This study aimed to assess the efficacy of colistin versus tigecycline, carbapenem monotherapy and combination in the treatment of BSI-KP. Electronic databases such as PubMed, Web of Science and Embase were searched. The last search was in November 24th, 2022, addressing the colistin, carbapenems and tigecycline monotherapy and combination treatments in patients with BSI-KP. The primary outcomes were 30-day or 28-day mortality. OR where available with 95% CI were pooled in random-effects meta-analysis. Following the outlined search strategy, a total of 658 articles were identified from the initial database searching. Six studies, 17 comparisons were included. However, they all were observational design, lacking high-quality randomized controlled trials (RCTs). Moderate or low-quality evidences suggested that colistin monotherapy was associated with an OR = 1.35 (95% CI = 0.62-2.97, P = 0.45, Tau2 = 0.00, I2 = 0%) compared with tigecycline monotherapy, OR = 0.81 (95% CI = 0.27-2.45, P = 0.71, Tau2 = 0.00, I2 = 0%) compared with carbapenem monotherapy. Compared with combination with tigecycline or carbapenem, Colistin monotherapy resulted in OR of 3.07 (95% CI = 1.34-7.04, P = 0.008, Tau2 = 0.00, I2 = 0%) and 0.98 (95%CI = 0.29-3.31, P = 0.98, Tau2 = 0.00, I2 = 0% ), respectively. Colistin, carbapenem and tigecycline monotherapy showed similar treatment effects in patients who suffered from BSI-KP. Compared with colistin monotherapy, colistin combined tigecycline therapy might play the synergism effects. retrospectively registered.