Long-term Clinical Experience Research Articles

The History and Impact of Prescribing Orthokeratology for Slowing Myopia Progression.

This paper discusses the history and impact of orthokeratology on slowing the progression of myopia. It discusses the origins and evolution of orthokeratology from polymethymethaccrylate lenses worn during the day to its current prescribing of highly permeable, innovative reverse-geometry designs worn only while sleeping. Technological advances in corneal topography, lens design, lens materials, and manufacturing have facilitated growth of orthokeratology to a precise and predictable procedure. More recently, significant interest in orthokeratology has been stimulated by its efficacy in slowing axial elongation in myopic children. Safety of children wearing contact lenses while sleeping has been an ongoing concern. The potential of serious complications exists, but long-term studies and clinical experience have shown that risks of those events can be minimized with strict compliance with lens cleaning, disinfection, and hand hygiene. Because no correction is required during waking hours, patients using orthokeratology report higher vision-related quality of life, less activity restrictions, and more comfortable eyes compared with spectacles or contact lenses worn during the day. The future growth of orthokeratology will be fueled by the prescribing of orthokeratology as a modality to slow axial elongation and an alternative modality to spectacles, traditional contact lenses, and refractive surgery to correct refractive error.

Copolymer liquid embolization of dural arteriovenous fistulas: A 20-year single-center experience.

Dural arteriovenous fistulas (DAVFs) with cortical venous drainage (CVD) carry significant risks of cerebral ischemia and intracranial hemorrhage. Endovascular treatment (EVT) using Onyx, a copolymer-based liquid embolic material, has become the preferred approach. However, the optimal treatment strategy for anterior cranial fossa DAVFs remains debated. This retrospective study analyzed outcomes of EVT for DAVFs in a single center from 2002 to 2023. Patient data including demographics, clinical status, angiographic findings, embolization techniques, and outcomes were recorded. The results of the anterior fossa malformations were analyzed separately afterward. A total of 195 DAVFs were included in the study. The most common presenting symptom was hemorrhage (41%), most fistulas were located in the transverse and sigmoid sinus region (48%), and the majority of DAVFs had direct CVD (78%). Transarterial embolization with Onyx was the preferred treatment strategy in majority of cases (92%). Overall, 94% of patients showed improvement or stability on the modified Rankin Scale. Two patients died due to rebleeding after partial DAVF embolization. Onyx demonstrated higher immediate complete occlusion rate compared to other embolic materials (88% vs. 35%). Overall, 91% of fistulas were closed at the last follow-up. Ten anterior fossa DAVFs were treated, resulting in clinical improvement and complete occlusion in all cases. Based on the results of our study, we believe that a cure of DAVFs, including those in the anterior fossa, can be achieved in more than 90% of cases through transarterial Onyx embolization, given long-term clinical experience.

Effectiveness and safety of ustekinumab for the treatment of psoriasis; six years of clinical experience

BackgroundThis work aimed to investigate the long-term clinical experience with ustekinumab in cases with psoriasis.Materials and methodsThis retrospective cohort research group consisted of cases who presented to the dermatology outpatient clinics between January 2015 and January 2021, diagnosed with psoriasis, and were treated with ustekinumab. Data including gender, age, weight, disease duration, naïve and non-naïve status, psoriasis type, duration of medication, comorbidities, psoriasis area and severity index scores, the causes of treatment discontinuation, and previous treatments were retrospectively reviewed and analyzed.Results160 cases with psoriasis were treated with ustekinumab during the research period. Twenty-four patients were excluded. Among 136 cases, 84 (61.8%) were male and 52 (38.2%) were female. We determined 80.55% of the non-naïve cases responded to ustekinumab.ConclusionUstekinumab can be a suitable treatment option for non-naïve and resistant patients. Our data suggest the positive effect persists in cases with favorable responses to the first or second dose of ustekinumab. Also, we determined male cases gave more rapid and more robust responses than female cases, and patients were more willing about continuing the treatment.

Administration of Oxycodone Hydrochloride by Target Controlled Infusion - Does the Timing Matter?

Background: In spite of long-term clinical experience with oxycodone hydrochloride/OxyNorm (OH), analgesic concentrations of OH in acute postoperative pain management have not been established. There are assumably different opinions regarding intraoperative timing of OH administration among anaesthesiologists and nurse anaesthetists, hence different practices. Aim: The aim of the study was to determine to which extent intraoperative timing of OH administration affects the need for postoperative OH during target-controlled propofol and remifentanil infusion (TCI) for patients undergoing laparoscopic cholecystectomy. Method: Anesthetic and postoperative journals from 100 patients were included in this retrospective observational study. Patients in category 1 (n = 20) received OH towards the end in addition to the introduction/maintenance of TCI. Patients in category 2 (n = 66) received OH in the beginning/during the maintenance of TCI, but not towards the end. Patients in category 3 (n = 14) received OH only towards the end of TCI. Multiple regression models were used to analyze the data. Result: Mean total postoperative doses of OH and standard deviations (SD) were 4.7 (3.1), 6.9 (5.1) and 4.7 (3.4) mg for patients in categories 1–3, respectively; with an overall p-value for equality of group means of 0.032. Adjusting for age, gender, weight, operating time and medications given during operation did not affect the results substantially (p = 0.012). In total during the per- and postoperative course, observed means (SD) of OH administered were 11.0 (2.9), 12.1 (5.5) and 9.0 (3.5) mg for patients in categories 1- , respectively (p = 0.039). The estimated group differences were only slightly affected by adjusting for patient and operational variables, however the result was no longer statistically significant (p = 0.057). Conclusion: Our retrospective analysis suggested that intraoperative timing of OH administration affects the need for OH postoperatively after laparoscopic cholecystectomy with TCI anaesthesia. To reduce the total amount of OH, it may be beneficial to administer OH only towards the end of anaesthesia.

Medical therapy with flecainide and propafenone in atrial fibrillation: Long-term clinical experience in the tertiary care setting.

Flecainide and propafenone are Class Ic antiarrhythmic drugs that block the cardiac fast inwards Na+ current and are used for rhythm control in patients with atrial fibrillation (AF). However, data on long-term clinical efficacy and safety of these drugs in a real-world setting are scarce. Patients with AF who received chronic flecainide or propafenone therapy were retrospectively studied from the database of a tertiary care center. The primary outcome of the study was clinical efficacy of Class Ic antiarrhythmics, which was assessed based on the improvement of arrhythmia-related symptoms at the time of last follow-up. Among the 361 patients (261 males, 72.3%) with a mean age of 56 ± 12 years, 287 (79.5%) were using long-term flecainide, and 74 (20.5%) patients propafenone. The majority of the patients had paroxysmal AF (n = 331, 91.7%) and had an atrioventricular-nodal blocking co-medication (n = 287, 79.5%). A total of 117 (32%) patients discontinued therapy after a median of 210 days (interquartile range 62-855 days). Clinical efficacy was observed in 188 (52%) patients. The most common reason for therapy discontinuation was adverse drug effects, particularly proarrhythmic effects (48% for flecainide and 33% for propafenone). Patients who did not clinically benefit from Class Ic antiarrhythmics more often underwent pulmonary vein isolation (p = 0.02). Long-term therapy with Class Ic antiarrhythmics showed clinical efficacy in approximately half of the patients with paroxysmal or persistent AF. However, these drugs were also associated with a relatively high rate of adverse events, and in particular proarrhythmic effects, which often resulted in therapy discontinuation rendering appropriate patient selection and therapy surveillance essential.

Salt processing: A unique and classic technology for Chinese medicine processing.

Traditional Chinese medicine (TCM) processing is the summary of long-term clinical experience, processing can change the property, taste and meridian of TCM, achieve the purpose of reducing toxicity and increasing efficiency, to ensure the safety of clinical medication. This paper summarizes the research advance of salt processing in recent years from the aspects of the types of excipients, salt processing methods, salt processing purpose and the influence of salt process on the chemical composition, pharmacodynamic effect and in vivo behavior of TCM, and analyzes and discusses the shortcomings of the current research, so as to provide ideas for the further research and development of salt processing of TCM. The literatures were classified and summarized by consulting the scientific database (such as SciFinder Scholar, CNKI, Google Scholar, Baidu Scholar, etc.), Chinese herbal classics and Chinese Pharmacopoeia and so on. The results show that salt processing is helpful to introduce drugs into the kidney channel and enhance the effect of nourishing Yin and falling fire. The pharmacological effect, chemical composition and in vivo behavior of TCM will change after salt processing. In the future, we should strengthen the research on standardizing the dosage of excipients, the quality standard after processing, the relationship between the change of chemical composition after salt processing and the enhancement of pharmacological efficacy, so as to deeply explain the principle of salt processing, and further improve and optimize the salt making process. By combing the influence of the of salt processing of TCM and analyzed the current problems, we hope to provide guidance for the in-depth study of the salt processing mechanism of TCM and the inheritance and innovation of TCM processing technology.

ASP210 - a Potent Oligonucleotide-Based Inhibitor for Combating Both BCR-ABL1 Dependent and Independent TKI-Resistant CML Cells

Background: Tyrosine kinase inhibitors (TKIs) have remarkably changed the management of Ph+ chronic myeloid leukemia (CML) and have dramatically contributed to substantial prolongation of survival rates and superior quality of life. However, long-term clinical experience with TKIs shows that despite the apparent therapeutic benefit, ~35% of CML patients exhibit primary resistance or intolerance to TKIs, and ~25% of those treated is forced to switch TKI at least once during therapy due to acquired resistance. Mutations in the kinase domain of BCR-ABL1 are the most comprehensively described mechanism of TKI-resistance but fail to explain ~40% of resistant cases. Nevertheless, due to the availability of several TKIs, the issue of TKI-resistance has de facto reduced to the mutation T315I and BCR-ABL1 independent resistance. TKI-resistance thus represents a persistent clinical problem to be solved and ultimately calls for alternative treatment solutions for CML patients with leukemic clones escaping TKI therapy. Oligonucleotide therapeutics have generated high expectation stemming from their potency and the field has seen great advancements leading to an apparent progress in clinical trials. Given the vastly different molecular target compared to protein inhibitors (RNA versus protein) as well as principally different mechanism of action, oligonucleotide therapeutics might represent rational and potent tools to combat TKI-resistant CML cells. Progress beyond the state-of-the art: The design of standard oligonucleotides is relatively straightforward and is sequence driven. However, the promiscuity of oligonucleotides places severe limitations on this approach since sequence-dependent off-target effects deteriorate their toxicological profile. Unconventionally, we considered additional parameters during the design of an oligonucleotide-based inhibitor, including steric and thermodynamic aspects of its binding to the target RNA, which significantly improved its safety. Here we report on a potent, safe, and highly specific oligonucleotide-based modality against BCR-ABL1 mRNA, ASP210, which effectively induces apoptosis in both BCR-ABL1 dependent and independent TKI-resistant CML cells. Methods:BCR-ABL1 positive cell lines MOLM-7 a CML-T1, both sensitive and resistant to TKIs imatinib and dasatinib were used to investigate the efficacy of ASP210, a biotinylated 34mer phosphorothioate DNA with an internal poly(ethylene glycol) linker. Briefly, MOLM-7 and CML-T1 cells and their resistant sub-lines were incubated with defined concentrations of ASP210 ranging between 0.25-5.0 µM for 10 days (applied once daily). Cell viability was monitored by trypan blue staining every day. The results were normalized to control, i.e., to untreated cells on the respective day. Of note, MOLM-7 TKI-resistant cells did not possess any mutation in the kinase domain, while both resistant sub-lines derived from CML-T1 harbored the clinically relevant mutation T315I. BCR-ABL1 negative cell line HL-60 was used as target negative control in the same experimental setup. Results:In vitro functional tests of ASP210 revealed its ability to induce cell death of all BCR-ABL1 positive cell types studied. A continuous decrease in the viability of ASP210-exposed cells has been observed already after 24 hours in all cell types including both TKI-sensitive CML cells and the derived TKI-resistant sub-lines irrespective of their T315I status. The efficacy of ASP210 was confirmed to be dose-dependent, with ASP210 causing a ~90% reduction of CML cells by day 5. Importantly, no effect on the viability of BCR-ABL1 negative HL-60 cells was observed (viability remained ≥95%) upon exposure to ASP210. Conclusions: The present study demonstrates the cytoreductive potential of ASP210 in terms of its ability to induce apoptosis in both BCR-ABL1 dependent and independent TKI-resistant CML cells, with no effect on BCR-ABL1 negative cells.

A classification method for multi-class skin damage images combining quantum computing and Inception-ResNet-V1

Melanoma is a high-grade malignant tumor. Melanoma and mole lesions are highly similar and have a very high mortality rate. Early diagnosis and treatment have an important impact on the patient’s condition. The results of dermoscopy are usually judged visually by doctors through long-term clinical experience, and the diagnostic results may be different under different visual conditions. Computer-aided examinations can help doctors improve efficiency and diagnostic accuracy. The purpose of this paper is to use an improved quantum Inception-ResNet-V1 model to classify multiple types of skin lesion images and improve the accuracy of melanoma identification. In this study, the FC layer of Inception-ResNet-V1 is removed, the average pooling layer is the last, SVM is used as the classifier, and the convolutional layer is quantized. The performance of the model was tested experimentally on the ISIC 2019 dataset. To prevent the imbalance of the sample data set from affecting the experiment, the sample data is sampled with weight. Experiments show that the method used shows excellent performance, and the classification accuracy rate reaches 98%, which provides effective help for the clinical diagnosis of melanoma.

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy

BackgroundTo review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT).MethodsFrom April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28–30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0.ResultsAmong the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153).ConclusionDistant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

The potential of heparin-induced extracorporeal LDL/fibrinogen precipitation (H.E.L.P.)-apheresis for patients with severe acute or chronic COVID-19.

Patients with long COVID and acute COVID should benefit from treatment with H.E.L.P. apheresis, which is in clinical use for 37 years. COVID-19 can cause a severe acute multi-organ illness and, subsequently, in many patients the chronic illness long-COVID/PASC. The alveolar tissue and adjacent capillaries show inflammatory and procoagulatory activation with cell necrosis, thrombi, and massive fibrinoid deposits, namely, unsolvable microthrombi, which results in an obstructed gas exchange. Heparin-induced extracorporeal LDL/fibrinogen precipitation (H.E.L.P.) apheresis solves these problems by helping the entire macro- and microcirculation extracorporeally. It uses unfractionated heparin, which binds the spike protein and thereby should remove the virus (debris). It dissolves the forming microthrombi without bleeding risk. It removes large amounts of fibrinogen (coagulation protein), which immediately improves the oxygen supply in the capillaries. In addition, it removes the precursors of both the procoagulatory and the fibrinolytic cascade, thus de-escalating the entire hemostaseological system. It increases myocardial, cerebral, and pulmonary blood flow rates, and coronary flow reserve, facilitating oxygen exchange in the capillaries, without bleeding risks. Another factor in COVID is the “cytokine storm” harming microcirculation in the lungs and other organs. Intervention by H.E.L.P. apheresis could prevent uncontrollable coagulation and inflammatory activity by removing cytokines such as interleukin (IL)-6, IL-8, and TNF-α, and reduces C-reactive protein, and eliminating endo- and ecto-toxins, without touching protective IgM/IgG antibodies, leukocyte, or platelet function. The therapy can be used safely in combination with antiviral drugs, antibiotics, anticoagulants, or antihypertensive drugs. Long-term clinical experience with H.E.L.P. apheresis shows it cannot inflict harm upon patients with COVID-19.

Evaluation of the Safety of a GalaFLEX-AlloDerm Construct in Prepectoral Breast Reconstruction.

Prepectoral implant-based breast reconstruction is gaining in popularity. Acellular dermal matrices are an integral part of prepectoral reconstruction. However, large quantities of acellular dermal matrix are required for total implant coverage, and the cost of acellular dermal matrices could be a deterrent to reconstruction. To minimize the cost, the authors have resorted to the use of a bioabsorbable mesh, GalaFLEX, as a partial replacement to acellular dermal matrices. This study evaluates the comparative safety of using a GalaFLEX-AlloDerm construct versus AlloDerm alone in prepectoral reconstruction. Consecutive patients who underwent immediate, expander-implant, prepectoral breast reconstruction were included in this retrospective study. Patients were stratified into two groups: those who received the GalaFLEX-AlloDerm combination versus AlloDerm alone. In GalaFLEX-AlloDerm reconstructions, the lower third of the expander was covered by the AlloDerm, whereas the rest of the expander was covered by GalaFLEX. Complications following reconstruction were compared between the groups. AlloDerm alone was used in 128 patients (249 breasts) and GalaFLEX-AlloDerm was used in 135 patients (250 breasts). The rate of any complication was 7.6 percent in the AlloDerm-alone group and 6.4 percent in the GalaFLEX-AlloDerm group. The rate of infection, major skin necrosis, seroma, capsular contracture, prosthesis exposure/extrusion, and prosthesis loss were less than or equal to 3.0 percent in the GalaFLEX-AlloDerm group and did not differ significantly from those in the AlloDerm-only group. GalaFLEX bioabsorbable matrix is a less costly alternative to acellular dermal matrices in two-stage, prepectoral reconstruction with comparable safety outcomes. Further long-term data and clinical experience are needed to better understand the safety of this matrix for use in breast reconstruction. Therapeutic, III.

Puerarin improves skeletal muscle strength by regulating gut microbiota in young adult rats.

BackgroundSarcopenia is an age-related skeletal muscle dysfunction syndrome that is lacking validated treatments. Maximizing muscle strength in young adulthood may be a promising way to prevent sarcopenia in the elderly. The phytomolecule puerarin has been extensively used in clinical practice and reported to increase energy metabolism in skeletal muscle by directly targeting the skeletal muscle fiber. However, the bioavailability of puerarin is very poor, and almost 93% of puerarin stays in the intestine until excretion. Therefore, we hypothesize that puerarin may regulate gut microbiota to improve skeletal muscle strength and/or mass in adults.MethodsTwenty three-month old male Sprague Dawley rats were divided into two groups according to average weights, puerarin group (puerarin dissolved in 0.5% CMC-Na, 150 ​mg/kg/day, N ​= ​10), and control group (equal volume 0.5% CMC-Na, N ​= ​10). The treatment lasted for 8 weeks. Muscle weight, muscle fiber types and cross-sectional area (CSA), ex vivo muscle contraction test and grip strength were measured. 16S rDNA sequencing was employed to evaluate the gut microbiota composition in the sample of cecal content. Short-chain fatty acids (SCFAs) in cecal and serum were analyzed by gas chromatography-mass spectrometry. Adenosine triphosphate (ATP) concentration in skeletal muscle was also detected. Pearson's correlation was used to analyze the relations between SCFAs, ATP concentration and muscle function.ResultsAfter puerarin treatment, grip strength, the specific twitch force, and the tetanic forces in the soleus (SOL) and extensor digitorum longus (EDL) muscle were significantly higher than those of the control group. The percentage and CSA of type II muscle fiber in EDL was higher in the puerarin group than those in the control group. Puerarin treatment significantly changed the gut microbial constitutes. Two SCFAs-productive microbiota, the families Peptococcaceae and Closteridiales, were significantly higher in the puerarin group than those in the control group, while the ratio of Prevotellaceae/Bacteroidaceae (P/B), a muscle atrophy indicator, was lower in the puerarin group. As expected, there were significant linear correlations between the concentrations of SCFAs, including cecal total SCFAs, serum n-butyric acid and total SCFAs, and skeletal muscle strength and function, including the twitch force and tetanic force of SOL and EDL, as well as the forelimb grip strength.ConclusionIn conclusion, puerarin improved the forelimb grip strength and muscle contraction function in young adult rats. The underlying mechanism may include that puerarin increased SCFAs production by regulating gut microbiota, augmented ATP synthesis and skeletal muscle strength.The translational potential of this article: Our study finds that a clinical used phytomolecule puerarin has the potential of improving skeletal muscle strength in young adult rats. As puerarin has long-term clinical experience and shows good safety, it might be a potential candidate for developing muscle strengthening agents.

Long-Term Clinical Experience with Directional Deep Brain Stimulation Programming: A Retrospective Review

IntroductionDirectional deep brain stimulation (d-DBS) axially displaces the volume of tissue activated (VTA) towards the intended target and away from neighboring structures potentially improving benefit and reducing side effects (SE) of stimulation. A clinical trial evaluating d-DBS demonstrated a wider therapeutic window (TW) with directional electrodes. While this seems advantageous, it remains unclear when and why directional stimulation is chosen clinically. To evaluate the implementation of d-DBS in our practice we examined the prevalence of and motivation for directional programming.MethodsA retrospective review was completed in consecutive patients with Parkinson’s disease (PD)/essential tremor (ET) implanted with the Abbott Infinity system from December 2016 to January 2020. At 3, 12, 24, and 36 months we extracted post-DBS stimulation parameters; use of directional electrodes and other advanced programming techniques; and reasons for directional programming.ResultsFifty-six patients with PD and 18 patients with ET (104 and 33 leads, respectively) were identified. The numbers of patients programmed with a directional electrode in at least one DBS lead in PD and ET, respectively, were 22/56 (39%) and 13/18 (72%) at 3 months; 19/48 (40%) and 8/12 (67%) at 12 months; 12/31 (39%) and 5/8 (63%) at 24 months; and 6/9 (67%) and 1/2 (50%) at 36 months. In PD and ET, reasons for using directional stimulation were better symptom control, less SE, or combination of better symptom control/SE; additional reasons in ET were improved battery/TW%.ConclusionOver a 36-month time period 39–68% of patients with PD and 50–72% of patients with ET had at least one lead programmed directionally in order to either improve symptom control or reduce side effects, an option not available with conventional omnidirectional stimulation. Initially directional electrodes were used in ET more frequently than PD, likely because of the less complex nature of programming for a monosymptomatic disorder. However, over time this shifted as we gained directional experience and sought solutions to reduce worsening symptoms.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-022-00381-5.

BCG in Bladder Cancer Immunotherapy.

Simple SummaryBacillus Calmette–Guérin (BCG), a live attenuated strain of Mycobacterium bovis, is the most successful microbial immunotherapy of cancer in current use. Intravesical treatment with BCG is recommended for most patients with high-risk non-muscle invasive bladder cancer (NMIBC). In patients with NMIBC, treatment with BCG is associated with reduced risk of bladder cancer recurrence and progression compared to transurethral resection alone. Here, we summarize current data regarding the mechanism of BCG and review indications and recommended practice for BCG treatment of bladder cancer.BCG is a live attenuated strain of Mycobacterium bovis that is primarily used as a vaccine against tuberculosis. In the past four decades, BCG has also been used for the treatment of non-muscle invasive bladder cancer (NMIBC). In patients with NMIBC, BCG reduces the risk of tumor recurrence and decreases the likelihood of progression to more invasive disease. Despite the long-term clinical experience with BCG, its mechanism of action is still being elucidated. Data from animal models and from human studies suggests that BCG activates both the innate and adaptive arms of the immune system eventually leading to tumor destruction. Herein, we review the current data regarding the mechanism of BCG and summarize the evidence for its clinical efficacy and recommended indications and clinical practice.

Octreotide in the treatment of acromegaly – the possibilities of high-dose therapy

Octreotide is a first-generation somatostatin analog that has been used for 40 years for the medical treatment of acromegaly, both after neurosurgical intervention and as first-line treatment. The frequency of biochemical control against the background of extended-acting octreotide varies from 25 to 56% depending on growth hormone and IGF-1 levels at the disease debut, presence of previous surgery, patient gender and age, treatment compliance and the dose of octreotide used. Longterm clinical experience with prolonged-acting octreotide demonstrates that more than half of patients require an increase in dosage to 30 mg or higher. If during treatment with Octreotide in a dose of 30 mg for 3 months there is no normalization of IGF-1 level, but there was a decrease of 50% or more of the initial level, further dose increase to 40 mg is possible, because this increases the effectiveness of treatment without increasing the frequency of side effects. Foreign researchers have shown that high doses of Octreotide (60 mg every 28 days) can improve biochemical control in patients who have not fully responded to therapy with doses of 30–40 mg of extended-acting Octreotide. Further studies are needed to determine the optimal dose of prolonged octreotide in acromegaly therapy, both at the start of treatment and during treatment. Management of patients by a team of specialists involved in the treatment of pituitary tumors will allow faster achievement of biochemical control of acromegaly.

Endovascular treatment of unruptured intracranial aneurysms with flow diverters: A retrospective long-term single center analysis.

The introduction of flow diverters (FDs) in 2007 greatly enhanced the treatment of intracranial aneurysms. Here, we present our long-term clinical experience in treating unruptured intracranial aneurysms with FDs. 107 patients with unruptured aneurysms and treated with an FD between 2010 and 2019 were retrospectively reviewed. Aneurysm occlusion, procedural complications, and clinical outcome were evaluated. Angiographic follow-up was available for 93 patients with a mean long-term follow-up time of 28.4 ± 21.6months. Additional coiling was performed in 15.1% of patients (n = 14). Adequate aneurysm occlusion (Kamran grades 3 and 4) at long-term follow-up was achieved in 94.6% of patients (n = 88). 3.2% (n = 3) required endovascular retreatment since the last follow-up showed a lack of aneurysm occlusion (Kamran grade 0) due to a foreshortening of the FD. Incomplete opening of the FD and parent vessel occlusion was seen in 1.1% (n = 1) and 3.2% (n = 3) of patients, respectively. In-stent stenosis was observed in 57% (n = 53) of cases at short-term follow-up and 22.6% (n = 21) at long-term, which were moderate and asymptomatic overall. In-stent stenosis decreased significantly between short- and long-term follow-ups (31.4 ± 17.0% vs 9.7 ± 13.6%, respectively; p ≤ 0.001). Thromboembolic and hemorrhagic events occurred in 7.5% (n = 7) and 1.1% (n = 1) of patients, respectively. Good clinical outcome (modified Rankin scale: 0-2) was obtained in 97.8% (n = 91) leading to an overall treatment-related morbidity of 2.2% (n = 2). There was no procedural mortality. Our study shows that FD treatment of unruptured intracranial aneurysms is effective and safe with high occlusion rates and low rates of permanent morbidity at long-term follow-up.

Femtosecond Intrastromal Lenticule Implantation (FILI) for Management of Moderate to High Hyperopia: 5-Year Outcomes.

To report the long-term clinical experience following femtosecond intrastromal lenticule implantation (FILI) for the management of moderate to high hyperopia. Eligible patients who underwent FILI for moderate to high hyperopia from July 2013 to October 2020 were included. A donor small incision lenticule extraction lenticule, matched for refractive error, was implanted into the recipient's corneal pocket created using a femtosecond laser at 160 µm depth. Visual and refractive outcomes and long-term complications were evaluated at the end of a mean follow-up of 68 ± 17.28 months (5.6 years). Forty-two eyes of 25 patients (mean age: 27.29 ± 5.52 years) were analyzed. The mean spherical equivalent reduced significantly from +5.50 ± 1.96 to +0.66 ± 1.17 diopters (D) at last follow-up visit. Thirty eyes (71%) were within ±1.00 D of spherical equivalent correction. Cumulative uncorrected distance visual acuity of 20/40 or better was achieved in 34 eyes (81%). Efficacy and safety indices were 0.86 ± 0.19 and 1.17 ± 0.39, respectively. There was a significant increase in mean keratometry (Kmean) anterior, central corneal thickness, Q-value, and corneal higher order aberrations and a decrease in Kmean posterior 2 weeks postoperatively, without any significant change in these parameters thereafter (P > .05). Four eyes of 3 patients underwent enhancement and another 4 eyes underwent explantation of the lenticule followed by exchange (2 eyes) and hyperopic laser in situ keratomileusis (2 eyes). No eye lost more than one line of CDVA. At 5 years of follow-up, FILI for moderate to high hyperopia showed good safety, efficacy, and reversibility. Modification of nomograms and surgical planning may be employed for further refinement of the outcomes. [J Refract Surg. 2022;38(6):348-354.].

Optical coherence tomography in the diagnosis and monitoring of congenital and juvenile glaucoma

Optical coherence tomography (OCT) in everyday routine practice is the method of choice for the instrumental diagnosis of glaucoma in adults. As a non-invasive and safe method of visualizing structural changes in the retina and the optic nerve, the method is of particular value in pediatric practice. At the same time, OCT diagnostics in children is associated with certain difficulties, both during the study and when interpreting the scan results.This review summarizes the data from the literature and our own research in the diagnosis and monitoring of congenital and juvenile glaucoma from the standpoint of our own long-term clinical experience in using optical coherence tomography. We consider the physiological changes of the retina and optic nerve, attention is focused on the need to create a pediatric regulatory database of retinal thickness, the factors that determine the normal range of the data obtained and allow distinguishing physiological processes from pathological ones are identified. Clinical cases confirming the value of OCT in combined pathology are presented as examples.

Effects and related mechanisms of Huang's SiYu pills on Leydig cell function in kidney-yin deficiency rat models

The prescription “Huang's SiYu Pill” (HSYP) was founded by professor Huang Haibo, a famous traditional Chinese medicine in Inner Mongolia, based on long-term clinical experience. In this study we observed the effects of HYSP on sperm quality, hormone level and the expression level of reproductive related genes and proteins in testicular stromal cells of rats with kidney-yin deficiency to explore the therapeutic mechanism of HSYP in the treatment of infertility with kidney-yin deficiency, Liuwei Dihuang Pill group (LDP) and Tamoxifen Citrate Tablets combined with Pancreatic Kallidinogenase Enteric Coated Tablets were used to be the positive control drug. After 25 days of medicine administration, the animals were anesthetized and killed, the serum and testicular tissues were retained for further experiments. The ELISA results showed that HSYP had a better effect on increasing serum FSH level than the conventional Chinese medicine or western medicine, while there was no remarkable difference in the regulation of serum LH in each administration group. The results of RT-qPCR showed that the transcription levels of Cyp11a1, Hsd3b1, Lhcgr and Star genes in the medium and high dose groups of HSYP were significantly upregulated compared with the model group of kidney-yin deficiency, while the expression of Nr5a1 gene was not significantly affected. The results of HE and immunohistochemistry showed that HSYP significantly improved the development level of testicular stromal cells and promoted the expression levels of CYP11A1 and HSD11B1 in testicular stromal cells, compared with the model group of kidney-yin deficiency. Together, our results showed that Huang's SiYu Pills can significantly improve the development and function of Leydig cells in SD rats with kidney-yin deficiency model, which provided a good research basis for deep research on relevant pharmacological mechanisms of the medicine.

Диагностика и лечение бактериальных, хламидийных и аденовирусных конъюнктивитов

In the review article, based on the analysis of modern literature data and own long-term clinical experience, some practical issues of conjunctivitis are presented, which continue to be an urgent problem of modern ophthalmology. In particular, this paper presents modern methods of diagnosis and treatment of the most common conjunctivitis, namely, we are talking about bacterial, chlamydial and adenoviral lesions of the mucous membrane of the eye. At the same time, much attention is paid to antibiotic therapy of bacterial and chlamydial conjunctivitis, in which a special place is occupied by antibiotics- fluoroquinolones, which have a wide spectrum of action and are the first choice drugs for bacterial and chlamydial conjunctivitis, especially resistant to other antibiotics. Keywords: bacterial, chlamydial, adenoviral conjunctivitis, diagnosis, treatment.