Botox: Avoiding Pitfalls

OnabotulinumtoxinA (Botox®) is extremely safe with an LD50 of 3,500 units in humans. Despite a high safety profile, non-life-threatening complications can be frequent and frustrating to both the patient and the physician. Proper understanding of oculofacial anatomy is paramount to correctly understand the indications and proper administration of botulinum toxin. Botulinum toxin injections will not address skin pigmentation/quality, excess skin, contour deformities, volume loss/deformities, or tissue drop. Therefore, it is ideal for recruiting cosmetic surgery to the oculofacial practice.

Ferrocene and glucose oxidase-installed multifunctional hydrogel reactors for local cancer therapy.

For decades, implant-based breast augmentation has been one of the most performed surgical procedures for cosmetic purposes around the world. Hence, novel manufactured implants should be critically investigated to prove them safe and effective. Here, the authors describe the first independently conducted clinical study on Nagor Impleo textured round breast implants. For this retrospective study, outcomes of 340 consecutive female patients undergoing primary cosmetic breast augmentation were analyzed. Demographic and surgical data as well as outcomes and complications were evaluated. Furthermore, a survey concerning effectiveness and aesthetic satisfaction after breast augmentation was examined. All 680 implants were placed in a submuscular plane with incisions at the inframammary fold. The main indications for surgery were hypoplasia and hypoplasia with asymmetry. The mean implant volume was 390 cc and the main type of projection was high profile. The most common complications were hematoma and capsular contracture (0.9 percent, respectively). The overall revision rate for complications was 2.4%. Additionally, almost all patients showed increased quality of life and aesthetic satisfaction after a breast augmentation. Hence, all patients would undergo breast augmentation again with these newly launched devices. Nagor Impleo implants demonstrate a low complication rate and high safety profile. Although high aesthetic satisfaction and quality of life results were achieved, analysis of an even larger series over a longer period of time would be beneficial to evaluate the reliability of this implant.

A Descriptive Study to Evaluate Super Dimension Utilized for Incidental Pulmonary Nodules in a Community Hospital Setting

The SARS-CoV2 virus, the causative agent for COVID-19 disease has to lead to more than 3.1 million deaths and crossed 146 million infections worldwide so far. Although vaccines development and emergency authorization has been approved by several governments, there has been great concern about its side effects for the long term and its effectiveness against new mutated strains. A resurgence of COVID-19 or related disease can be catastrophic. There is an urgent need to look for effective antiviral agents for many coronavirus strains with minimum side-effects, and maximum efficacy globally. Several, naturally-derived biomolecules have proved their excellent effect on several infectious diseases in a multi-mode fashion by targeting several pathways as well as increasing efficacy with high safety profile. Integrate computational prediction design was used in the study to examine the pharmacology of bioactive compounds of natural origin against SARS-CoV2 spike protein. Keeping these facts we have computationally examined 16 naturally occurring compounds using to evaluate their effectiveness against the SARS-CoV2 virus using the molecular docking technique. Hesperidin derivatives are known to ameliorate diabetes, co-morbidity for coronavirus, as well as help in preventing post coronavirus complications. We found the binding free energy of Hesperidin with spike protein to be -7.57 kcal/mol, the aglycone derivative to be -6.93 kcal/mol, hesperidin monoacetyl derivative to be -7.82 kcal/mol, and hesperidin pentaacetyl derivative to be -8.39 kcal/mol. Our findings revealed that acetylated derivatives of hesperidin showed significant improved remarked binding affinity while aglycone derivative hesperetin showed a decrease in binding affinity. Our studies give a new direction where natural bioactive compounds and their derivatives can be modulated and used after clinical trials to effectively inhibit coronavirus infection as well as diabetes simultaneously with a high safety profile. Graphical Abstract

Simple SummaryIn recent years, chimeric antigen receptor (CAR)-T-cell therapy has achieved good results in hematological malignancies. Clinical trials on anti-MSLN CAR-T cells have shown that they have a high safety profile but limited efficacy. This article reviews the clinical research status, obstacles, progress and challenges of anti-MSLN CAR-T-cell therapy and summarizes the relevant strategies to improve the efficacy and safety of anti-MSLN CAR-T-cell therapy.Chimeric antigen receptor (CAR)-T-cell therapy is a kind of adoptive T-cell therapy (ACT) that has developed rapidly in recent years. Mesothelin (MSLN) is a tumor-associated antigen (TAA) that is highly expressed in various solid tumors and is an important target antigen for the development of new immunotherapies for solid tumors. This article reviews the clinical research status, obstacles, advancements and challenges of anti-MSLN CAR-T-cell therapy. Clinical trials on anti-MSLN CAR-T cells show that they have a high safety profile but limited efficacy. At present, local administration and introduction of new modifications are being used to enhance proliferation and persistence and to improve the efficacy and safety of anti-MSLN CAR-T cells. A number of clinical and basic studies have shown that the curative effect of combining this therapy with standard therapy is significantly better than that of monotherapy.

Cancer microenvironment is characterized by severe hypoxia and nutrient deprivation, especially glucose. Cancer depends largely on glycolysis for energy production (Warburg effect), therefore tumor hypoxia is mainly caused by poor blood supply despite vigorous angiogenesis. Severe tumor hypoxia and glucose deprivation promote tumor progression and affects tumor behavior especially resistance to anticancer drugs. We have focused on the invention of agents that cancel cancer cells' ability to tolerate poor oxygen and glucose supply (antiausterity) and found many agents including kigamicin, pyrvinium pamoate, and arctigenin. Because antitumor activity and safety profile were excellent in preclinical test, arctigenin was chosen for the first compound for clinical trial. Arctigenin is rich in fruit of Arctinum lappa which is filed in Japanese Pharmacopoeia, we have invented an extraction method to enrich arctigenin (GBS-01, Kracie Pharma, Ltd.) and used in clinical trial. GBS-01 contained arctigenin about 10% in weight. Pancreatic cancer is characterized for its hypovascularity and severe hypoxia in cancer tissue has been reported and, in addition, only limited benefit of chemotherapy has been achieved so far. Patients, material and design of trial: Pancreatic cancer patients refractory to gemcitabine were selected for the phase I clinical trial of GBS-01. Primary endpoint of the trial was determination of recommended dose by assessing DLT in dose escalation study from 1 g/day to 4 g/day, corresponding to 100 mg to 400 mg arctigenin/day. GBS-01 administration was continued until either unacceptable adverse effcts or evident progression of the cancer appeared. Pharmacokinetic study was also carried out as a secondary endpoint. Results:Fifteen patients were enrolled and three patients were not evaluated because of early stopping due to progression of the disease. Results: Among 12 patients evaluated, no DLT was observed. No serious adverse effects on bone marrow, liver and kidney function was observed. Pharmacokinetic study revealed that arctigenin is efficiently absorbed and rapidly conjugated with glucuronic acid. Serum concentration of arctgenin glucuronide was about 100 to several hundreds higher than that of arctigenin, indicating glucuronidation in the first pass. Urinary secretion of arctigenin and its glucuronide was more than half of administered dose in more than half of patients, indicating high bioavailability. Regarding clinical tumor response, partial response was observed in one patient at 2.5 g/day (level 2) for 2 months followed by 2four months stable disease (SD) and SD was observed in other four patients. Median progression free survival was 1.05 months and median overall survival was 5.68 months.Conclusion: Arctigenin showed high bioavailability, high safety profile, and promising clinical responses. Citation Format: Hiroyasu Esumi, Satoshi Owada, Rumi Fujioka, Katsuya Tsuchihara, Atsushi Ohtsu, Aihiro Sato, Masafumi Ikeda, Nobuo Mochizuki, Satoshi Kishino, Takanori Kawashima, Satoshi Yomoda. Arctigenin, an antiausterity agent shows high safety and promising clinical response in phase I clinical trial in patient with gemcitabine-refractory pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT213. doi:10.1158/1538-7445.AM2014-CT213

Background: Excessive skin is a side-effect of massive weight loss. The only evidence-based treatment for excessive skin is plastic surgery. Non-invasive treatments, therefore, need to be evaluated. The aim of this study was to investigate effects of therapeutic ultrasound treatment on excess skin on the upper arms after bariatric surgery. Method: Fourteen patients were randomised to receive five treatments, each lasting for 30 minutes with active ultrasound treatment by CellsonicTM (Cellsonic Ltd) on one arm. The other arm served as control. The effect was evaluated objectively by measuring arm volume, circumference, and ptosis, and subjectively by a questionnaire where the patients assessed the effect of the treatment and amount and/or discomfort of the excess skin. Result: No statistical differences were observed in the objectively measured variables. Some patients reported perceived effects and a majority reported positive experiences of the treatment. No side-effects were reported. Conclusion: This study could not find any objectively measured effect of ultrasound treatment on excessive skin after bariatric surgery. However, participants experienced relief of symptoms associated with excess skin, such as pain, looseness, and decreased skin burst, which indicates that ultrasonic treatment of patients with excessive skin should be further investigated.

Research in the development of new therapeutic agents with a wide spectrum of the antiviral activity and a low ability to develop resistance remains the main dimension in combating the global threat to public health. The need for a parenteral form of favipiravir was dictated by the necessity to increase the efficacy of therapy in COVID-19 inpatients. This dosage form has expanded the possibilities of drug therapy in the inpatients, for whom a therapeutic effect acceleration and a high safety profile of the drugs used are especially important.The aim of the article is the evaluation of the efficacy and safety of a medicinal product containing favipiravir for the parenteral administration against the background of pathogenetic and symptomatic therapy, in comparison with standard therapy in hospitalized COVID-19 patients.Materials and methods. An open, randomized, multicenter comparative study was conducted in 6 research centers in the Russian Federation to evaluate the efficacy and safety of favipiravir, a lyophilisate for the preparation of a concentrate for the infusion solution administrated to the patients hospitalized with COVID-19. Screening procedures and randomization were completed in 217 patients, 209 of which had completed the study in accordance with the protocol.Results. Between the study groups, statistically significant differences have been found out, making it possible to consider the hypothesis of the drug Areplivir (favipiravir) superiority for the parenteral administration over the standard therapy, which included favipiravir (p. o.) and remdesivir. A comparative analysis has shown that a course of therapy with the parenteral favipiravir drug leads to a significant improvement in the condition of patients with COVID-19, significant benefits in terms of the speed and frequency of improvement in the clinical status of patients, as well as a reduction in the hospital stay length. It has been proven that therapy with a drug containing favipiravir for the parenteral administration does not adversely affect the parameters of clinical and biochemical blood tests, urinalysis, coagulograms, vital signs and ECG, which indicates the therapy safety. The study drug is characterized by a high safety profile and tolerability.Conclusion. The versatility and resistance to mutations of RNA-dependent RNA polymerase make it possible to consider it as the main target for combating the most common RNA viruses that cause ARVI, that determines the need further studies of favipiravir to expand the range of its indications.

Imiquimod is being investigated as a therapeutic option for the management of actinic keratosis. Three recent clinical trials have demonstrated a reasonable efficacy rate and high safety profile. 'Cycle' therapy may improve the safety profile while maintaining efficacy. 'Field' treatment with imiquimod may uncover and treat 'subclinical' actinic keratoses, which in turn may potentially result in fewer recurrences. Longer follow-up studies are required to investigate this possibility.

Saccharumoside-B and its analogs were found to have anticancer potential in vitro. The present study reports acute toxicity, molecular docking, ADMET profile analysis, and in vitro and in vivo anti-inflammatory activity of saccharumoside-B for the first time. The in vitro enzyme inhibitory activity of saccharumoside-B on PLA2, COX-1, COX-2, and 5-LOX enzymes was evaluated by the cell-free method, and its effect on TNF-α, IL1β, and IL- 6 secretion levels in LPS stimulated THP-1 human monocytes was determined by ELISA-based methods. The anti-inflammatory activity was evaluated in vivo by carrageenan-induced rat paw edema model. To test its binding affinity at the active site pockets of PLA2 enzymes and assess drug-like properties, docking experiments and ADMET studies were performed. Saccharumoside-B showed selective inhibition of the sPLA2 enzyme (IC50 = 7.53 ± 0.232 μM), and thioetheramide-PC was used as a positive control. It showed significant inhibition (P ≤ 0.05) of TNF-α, IL-1β, and IL-6 cytokines compared to the positive control dexamethasone. Saccharumoside-B showed a dose-dependent inhibition of carrageenan-induced rat paw edema, with a maximum inhibition (76.09 ± 0.75) observed at 3 hours after the phlogistic agent injection. Saccharumoside-B potentially binds to the active site pocket of sPLA2 crystal protein (binding energy -7.6 Kcal/Mol). It complies with Lipinski's Rule of Five, showing a promising safety profile. The bioactivity scores suggested it to be a better enzyme inhibitor. Saccharumoside-B showed significant PLA2 inhibition. It can become a potential lead molecule in synthesizing a new class of selective PLA2 inhibitors with a high safety profile in the future.

ABSTRACTImportanceRecurrent respiratory tract infection (RRTI) is common in children. Inappropriate RRTI treatment will lead to asthma and other diseases, thereby seriously affecting the growth and physical health of children. Immune function modulation can prevent and alleviate childhood RRTI. Yupingfeng (YPF), a patented traditional Chinese medicine (TCM), has immunomodulatory effects and is widely used in China to treat children with RRTI.ObjectiveTo evaluate the safety and efficacy of YPF monotherapy in treating children with RRTI.MethodsThis multicenter, randomized, double‐blind, double‐simulation, noninferiority clinical trial was conducted from January 2015 to August 2017, with an 8‐week treatment period and 52‐week follow‐up after the drug withdrawal. Children aged 2–6 years with RRTI meeting the inclusion and exclusion criteria were enrolled in 13 hospitals in China and divided randomly into three groups (2:2:1 ratio) to receive YPF, pidotimod, or placebo. The primary outcome was the proportion of RRTI returning to normal standard level during the follow‐up. The secondary outcomes were reduction in the number of RRTI recurrences, effect on clinical symptoms (in accord with TCM practice), effect per symptom, and safety. The trial was registered at the Chinese Clinical Trials Registry (www.chictr.org.cn) under the unique identifier ChiCTR‐IPR‐15006847.ResultsThree hundred and fifty‐one children were enrolled and randomly assigned to 3 groups; 124, 125, and 61 children in the YPF, pidotimod, and placebo groups, respectively, had completed the trial. During the follow‐up, the proportion of RRTI returning to normal standard level was 73.13%, 67.15%, and 38.81% with YPF, pidotimod, and placebo, respectively (P < 0.0001). The proportion of cases who returned to normal standard level in the YPF group was 34.32% higher than that in the placebo group. The safety profile did not significantly differ among the groups.InterpretationYPF granules were noninferior to the active control drug pidotimod oral solution for the treatment of RRTI in children, and were superior to placebo, with a high safety profile.

Conventional anesthesia for clavicular fracture surgery poses significant challenges. General anesthesia risks pulmonary complications, while traditional nerve blocks may cause diaphragmatic paralysis or motor impairment. Ultrasound-guided techniques improve precision, but standalone superficial cervical plexus or interscalene brachial plexus blocks often fail to fully anesthetize the deep clavicular region, especially in polytrauma patients. An optimized combined approach could provide effective analgesia while preserving respiratory and motor function. A 65-year-old male patient with a comminuted fracture of the middle right clavicle and multiple injuries underwent surgery with an ultrasound-guided selective supraclavicular nerve block (SSNB) combined with a modified clavipectoral fascial plane block (MCPB), referred to here as SSCPB. The supraclavicular nerve and clavipectoral fascia were precisely located using ultrasound, and 0.4% ropivacaine was administered, supplemented with dexmedetomidine and sufentanil. The patient maintained stable intraoperative vitals with no pain responses and preserved diaphragmatic/limb function. Postoperatively, analgesia was excellent (VAS 0-2 at rest, 3 on movement) without neurological compromise. The SSCPB technique achieves optimal anesthesia for mid-clavicular fracture surgery by combining SSNB with MCPB. This approach effectively prevents diaphragmatic paralysis and upper limb dysfunction, making it particularly suitable for patients with concomitant cardiopulmonary injuries or comminuted fractures. Characterized by its simplicity in operation and high safety profile (avoiding general anesthesia-related risks), SSCPB reduces opioid dependence and promotes postoperative recovery. However, more extensive clinical research is required to establish its long-term safety and efficacy profile, particularly in complicated acromioclavicular joint dislocations where adjunctive sedation or suprascapular nerve blocks might be indicated.

To evaluate the feasibility, safety, and efficacy of microwave ablation (MWA) of bone lesions with regard to local control and pain palliation. We reviewed 43 patients (23 males, 20 females) with 51 lesions (44 metastatic, 7 benign) treated with MWA from January 2016 to December 2023. Pain intensity was measured using the Visual Analogue Scale (VAS), SF-36 Bodily Pain Scale, and Patient Global Impression of Change (PGIC) from pre-operation to various follow-up stages. Adverse events were categorized according to the Society of Interventional Radiology (SIR) grading system. The procedure demonstrated 100% technical success. Grades I and III adverse events were observed in 8.3% (3/36) and 2.8% (1/36) of patients with metastatic disease, respectively. In those with benign lesions, no adverse events were reported. A significant reduction in pain was observed, with the VAS score decreasing by 74.3% from baseline to the last follow-up [6.7 ± 2.3 (range: 0-10) to 1.8 ± 2.3 (range: 0-7) (p < 0.001)] for metastatic patients, and from 5.7 ± 2.1 (range: 3-8) to 0 ± 0 (range: 0-0) by the final follow-up (p = 0.0011) for benign lesions. 77.8% (29/36) of metastatic patients, and all (7/7) benign patients were much or very much improved according to Patient Global Impression Change. Complete imaging response was achieved in 55.6% (20/36) of metastatic lesions. At last follow-up, 25% (9/36) had radiological evidence of recurrence, with a median recurrence time of 13 months (IQR: 8-14). Complete response was achieved in all benign lesions. MWA is a safe and effective treatment for pain management in patients with bone lesions. This study confirms the potential of microwave ablation as a treatment for bone lesions, providing significant pain relief with a favorable safety profile. Microwave ablation (MWA) significantly reduced pain scores in patients with bone lesions, maintaining pain relief over time. The procedure exhibited high technical success with minimal adverse events, indicating a high safety profile. Subgroup analysis revealed no significant differences in pain reduction among different procedural combinations over time.

Background: Glatiramer acetate (Copaxone) is an approved treatment for multiple sclerosis with high safety profile. We are reporting a case of Crohn's disease diagnosed in a patient with multiple sclerosis after Copaxone was stopped. Case: A 57-year-old man with history of multiple sclerosis diagnosed many years ago, in remission achieved by Copaxone for more than 2 years, presented with bloody diarrhea and anemia, He never had any similar symptoms in the past. The patient admitted that he had not been following with his neurologist and he stopped Copaxone 3-4 months before presentation for financial reasons. CT scan of the abdomen showed pancolitis. Subsequent colonoscopy showed moderate scattered colitis with submucosal hemorrhage, friability and edema (Figure 1). Biopsies showed acute on chronic inflammatory colitis with granulomas suggestive of Crohn's disease. The patient received tapering doses of steroids and was started on mesalamine, his symptoms resolved in 6 weeks.FigureDiscussion: Copaxone is approved drug for multiple sclerosis with relatively safe profile. There is good evidence of therapeutic benefits of Copaxone in treatment of inflammatory bowel disease (IBD) in animal models, however clinical trials are lacking. Case reports in literature, although very few, have some debate, as couple of them reporting potential benefits in Crohn's disease, with Copaxone helped inducing remission in those cases, while another case report posed the question of potential development of Crohn's disease as a side effect for Copaxone. Our case reports development of Crohn's disease after Copaxone was stopped. Experimental studies have shown that Copaxone has immunomodulating property to deviate the immune response from Th1-dominated to a Th2-mediated inflammation. This could favor the potential benefit of Copaxone in maintenance of remission for Crohn's disease. Conclusion: Copaxone, supported by animal models, could have a role in treatment of Crohn's disease. However randomized clinical trials are needed.