Application of parallel artificial membrane permeability assay technique and chemometric modeling for blood-brain barrier permeability prediction of protein kinase inhibitors.

Aim: This study aims to investigate the passive diffusion of protein kinase inhibitors through the blood-brain barrier (BBB) and to develop a model for their permeability prediction. Materials & methods: We used the parallel artificial membrane permeability assay to obtain logPe values of each of 34 compounds and calculated descriptors for these structures to perform quantitative structure-property relationship modeling, creating different regression models. Results: The logPe values have been calculated for all 34 compounds. Support vector machine regression was considered the most reliable, and CATS2D_09_DA, CATS2D_04_AA, B04[N-S] and F07[C-N] descriptors were identified as the most influential to passive BBB permeability. Conclusion: The quantitative structure-property relationship-support vector machine regression model that has been generated can serve as an efficient method for preliminary screening of BBB permeability of new analogs.

Comprehensive Evaluation of Quality of Life following Upper Eyelid Blepharoplasty: A Prospective Analysis.

Background and Objectives: Upper eyelid blepharoplasty is a surgical procedure that addresses both aesthetic and functional concerns, offering transformative potential for patients' overall well-being. This study systematically evaluates the comprehensive impact of upper eyelid blepharoplasty on patients' quality of life, employing rigorous methodologies and standardized assessment protocols. Materials and Methods: A prospective, randomized controlled trial was conducted, involving 348 patients aged 49 to 87 years. Patients were randomly assigned to receive either continuous or intradermal sutures following upper eyelid surgery. Validated FACE-Q questionnaires were used to assess various outcomes, including early-life impact, expectations, satisfaction with eyes, overall face satisfaction, satisfaction with the outcome, psychological function, social function, and adverse effects. Results: Results indicate significant improvements in multiple domains of patient-reported outcomes following upper eyelid blepharoplasty, including satisfaction with eyes, overall face satisfaction, satisfaction with the outcome, psychological function, and social function. Notably, no significant differences were observed between suturing techniques regarding patient satisfaction and well-being. Adverse effects were minimal and improved over time. Conclusions: The study underscores the transformative nature of upper eyelid blepharoplasty in enhancing patients' quality of life, addressing both cosmetic and functional concerns. Utilizing standardized assessment tools like the FACE-Q questionnaire facilitates a comprehensive understanding of treatment outcomes and enables patient-centered care. Overall, this research contributes to the growing evidence supporting the positive impact of upper eyelid blepharoplasty on patients' well-being, emphasizing the importance of continued research and standardized assessment protocols in advancing patient care in cosmetic surgery.

Trend of suicide by self-immolation in a 13-year timeline: was the COVID-19 pandemic a potentially important stressor?

Introduction: Self-immolation is an uncommon way of attempting and committing a suicide, with a fatality rate of 80%. The risk factors in self-immolation victims vary depending on demographic characteristics, socio-economic and cultural factors as well as religious beliefs. Whether the COVID-19 pandemic was a potentially important stressor for self-immolation is still unknown, with insufficient studies examining this issue. Therefore, in this study, we aimed to examine the trend of self-immolation in a 13-year timeline, and the potential association of COVID-19 pandemic with the increase in the incidence and severity of self-immolation injuries in Serbia in 2021. Materials and methods: The study included hospitalized patients due to intentional burns caused by self-immolation in the period from January 1, 2008 to December 31, 2021. Joinpoint regression analysis was used for the analysis of continuous linear trends of self-immolation cases with change points. Results: While a rising trend was observed in the 2008-2013 time segment, followed by a decline in the upcoming 2013-2016 time segment, a significant increase reached its maximum during COVID-19 pandemic (2021), with annual percent change of 37.1% (p = 0.001). A significant increase in the median number of cases per year was observed during 2021 compared to the previous periods (7.5 vs. 2). Frequency of patients with a psychiatric diagnosis vs. those without a psychiatric diagnosis was significantly higher during than before the COVID-19 period (66.7 vs. 36.1%, p = 0.046). Conclusion: In our study, a significant increase in the frequency of suicide attempts by self-immolation during COVID-19 pandemic was noticed. There was also an increased frequency of pre-existing psychiatric illness among patients during the pandemic period. With limited high-quality data available, the study adds to a rising body of evidence for assessment of outcomes of the pandemic on mental health and recognition of stressors for self-immolation.

Sinonasal Hamartoma and Chronic Laryngeal Edema Causing Severe Dyspnea.

Background: Sinonasal hamartomas, according to the 5th edition of the World Health Organisation classification of head and neck tumours are divided into respiratory epithelial adenomatoid hamartoma (REAH), seromucinous hamartoma and chondromesenchymal hamartoma. Seromucinous hamartoma are benign proliferations of small eosinophilic glands surrounded by fibrous stroma and cuboidal cells. Hamartomas of the nasal cavity and paranasal sinuses are rare entities, clinically presenting as sinonasal polyposis. Case Presentation: A 79- year-old female patient was referred to our emergency room due to severe dyspnea. Anterior rhinoscopy revealed unilateral greyish polypoid mass obstructing the middle, inferior and common nasal meatus. Systemic corticosteroids and oxygen therapy were administered under observation. Computerized tomographic imaging of the paranasal sinuses with contrast on all three planes showed an opacified polypoid mass in all meatus and the maxillary, anterior ethmoidal and sphenoidal sinus posteriorly extending to the choanae. On the coronal plane a widening of the olfactory clefts about 12 mm was described. FESS visualized that the polypoid mass originated from the posterior septum and extended to all meatus anteriorly and to the choanae posteriorly. The polypoid lesion was endoscopically completely excised. Histopathological analysis revealed a seromucinous hamartoma. Conclusion: Seromucinous hamartoma are rare benign tumors of the sinonasal region with potential of malignant alteration. Unfortunately, they share symptoms and clinical appearance with other benign conditions of the sinonasal region. Therefore, it is even more important to consider them as a differential diagnose.

The Role of Ketamine as a Component of Multimodal Analgesia in Burns: A Retrospective Observational Study.

Background: Burn wound dressing and debridement are excruciatingly painful procedures that call for appropriate analgesia-typically multimodal. Better post-procedural pain management, less opioid use, and consequently fewer side effects, which could prolong recovery and increase morbidity, are all benefits of this type of analgesia. Intravenously administered ketamine can be effective as monotherapy or in combination with opioids, especially with procedural sedation such as in burn wound dressing. Methods: This observational study investigated the effect of ketamine administered in subanesthetic doses combined with opioids during burn wound dressing. The study was conducted from October 2018 to October 2021. A total of 165 patients met the inclusion criteria. A total of 82 patients were in the ketamine group, while 83 patients were dressed without ketamine. The main outcome was the effect of ketamine on intraprocedural opioid consumption. The secondary outcome included the effect of ketamine on postprocedural pain control. Results: Patients dressed with ketamine were significantly older (p = 0.001), while the mean doses of intraoperatively administered propofol and fentanyl were significantly lower than in patients dressed without ketamine (150 vs. 220 mg, p < 0.001; and 0.075 vs. 0.150 mg, p < 0.001; respectively). Conclusions: Ketamine was an independent predictor of lower intraoperative fentanyl consumption, according to the multivariate regression analysis (p = 0.015). Contrarily, both groups of patients required postoperative tramadol treatment, while intraoperative ketamine administration had no beneficial effects on postoperative pain management.

Detecting thyrotropin receptor mRNA from peripheral blood of patients with differentiated thyroid cancer rules out non-aggressive cases.

BACKGROUND: Early diagnosis of thyroid cancer is hampered by the inability of fine-needle aspiration biopsy (FNAB) to accurately classify ∼30% of cases while preoperative cancer staging detects lymph nodal involvement in only half of cases. Liquid biopsy may present an accurate, non-invasive alternative for preoperative thyroid nodule assessment. Thyrotropin receptor (TSHR) mRNA, a surrogate marker for circulating cancer cells (CTC), may be an option for early detection of malignancy from peripheral blood, but requires methodological improvements. We aimed to investigate if TSHR mRNA can be detected in low sample volumes by employing an ultrasensitive method - droplet digital PCR (ddPCR). METHODS: Less than 5 mL of blood was collected from 47 patients with thyroid nodules (25 benign and 22 malignant). RNA was isolated from the fraction of mononuclear cells where CTCs segregate. Samples were analysed for the presence of TSHR mRNA by ddPCR. RESULTS: Thyrotropin receptor mRNA was detectable in 4 mL sample volumes, with the test having good specificity (80%) but modest diagnostic accuracy (68.1%). Combining TSHR mRNA with ultrasound features and FNAB diagnosis, the test reaches high rule-out performances (sensitivity = 90% and NPV = 88.2%). Strikingly, TSHR mRNA correctly classified all samples with thyroid capsule invasion, lymph node metastasis and extrathyroidal extension. If aggressiveness is defined using these parameters, TSHR mRNA test reaches 100% sensitivity and 100% NPV for detecting high-risk cases. CONCLUSIONS: Employing ddPCR for TSHR mRNA improves its measurement by enabling detection in sample volumes common for laboratory testing. The test displays high prognostic performance, showing potential in preoperative risk assessment.

Galectin-1 in Pancreatic Ductal Adenocarcinoma: Bridging Tumor Biology, Immune Evasion, and Therapeutic Opportunities.

Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most challenging malignancies to treat, with a complex interplay of molecular pathways contributing to its aggressive nature. Galectin-1 (Gal-1), a member of the galectin family, has emerged as a pivotal player in the PDAC microenvironment, influencing various aspects from tumor growth and angiogenesis to immune modulation. This review provides a comprehensive overview of the multifaceted role of Galectin-1 in PDAC. We delve into its contributions to tumor stroma remodeling, angiogenesis, metabolic reprogramming, and potential implications for therapeutic interventions. The challenges associated with targeting Gal-1 are discussed, given its pleiotropic functions and complexities in different cellular conditions. Additionally, the promising prospects of Gal-1 inhibition, including the utilization of nanotechnology and theranostics, are highlighted. By integrating recent findings and shedding light on the intricacies of Gal-1's involvement in PDAC, this review aims to provide insights that could guide future research and therapeutic strategies.

Primary Melanoma Histopathologic Predictors of Sentinel Lymph Node Positivity: A Proposed Scoring System for Risk Assessment and Patient Selection in a Clinical Setting.

Background and Objectives: The careful selection of adequate SLNB candidates not only aims at reducing the surgical risk while identifying SLN metastasis, but also plays a crucial role in identifying the patients eligible for adjuvant therapy. Objectives: The purpose of our study was to investigate the clinical and histologic aspects of primary melanomas that correlate with the likelihood of a positive SLNB result. Materials and Methods: A total of 101 primary melanoma patients who underwent sentinel lymph node biopsies were included in the study. General patient demographics were obtained as well as localization and melanoma-specific characteristics of primary melanoma from histologic reports in addition to data derived from SLNB melanoma histopathology reports. Results: The patients with positive SLN results had a statistically significant increased Breslow thickness (3.8 mm vs. 1.97 mm, p = 0.002), higher mitotic index rate (5/mm2 vs. 2/mm2, p = 0.009), as well as the presence of ulceration (68.4% vs. 31.6%, p = 0.007). Univariate regression analysis showed the Breslow thickness (p = 0.008), the mitotic index rate (p = 0.054), the presence of ulceration (p = 0.009), as well as the pT3-4 stage (p = 0.009) to be significant predictors of SLN positivity. The optimal cut-off values for Breslow thickness and the number of mitoses scores were determined based on ROC curve analysis. Using the Breslow thickness, mitotic index rate, presence of ulceration, and pT3-4 stage significant coefficients from the univariate regression model, a chance prediction score was developed. Conclusions: The newly developed and proposed scoring system can aid in patient selection for SLN biopsy by facilitating a more efficient risk assessment in the detection of lymph node metastases in melanoma patients.

Mathematical model of aging in COVID-19.

Background: The aim was examination of the intimamedia thickness of carotid arteries in COVID-19 infection. Methods: In 50 patients, the thickness of the intimomedial complex (IMT) in the common carotid arteries was measured. The values were compared with the control group in 2006-9. The condition of the lungs was assessed by ultrasound score (It score) (0-42) as mild (0-14) or mediumsevere (15-28) Covid. IMT thickening risk factors and the value of fibrinogen, IL-6 and CRP were recorded. Two IMT prediction models were formed. The socio-epidemiological model predicts the development of IMT based on epidemiological factors. Apart from these factors, the second model also includes the values of the mentioned biomarkers. Results: It score 20±6, IMT values right: median 0.99 mm, p25=0.89, p75=1.14; left: 1±0.22 mm. Control: IMTright: median 0.7 mm, p25=0.68 mm; p75=0-9 mm; left: median=0.75 mm, p25=0.6 mm, p75=1.0 mm. The group/control difference is highly significant. Epide mio - logical model: logit (IMT)= 4.463+(2.021+value for GEN)+(0.055x AGE value)+(-3.419x RF value)+(-4.447x SM value)+(5.115x HTA value)+(3.56x DM value)+ (22.389x LIP value)+(24.206x CVD value)+(1.449x other value)+(-0.138x It score value)+(0.19xBMI value). Epidemiological-inflammatory model: logit (IMT)=5.204+ (2.545x GEN value)+(0.076x AGE value)+(-6.132x RF value)+(-7.583x SM value)+(8.744x HTA value)+(6.838x DM value)+(25.446x LIP value)+(28.825x CVD value)+ (2.487x other value)+(-0.218xIt score value)+(0.649x BMI value) +(-0.194x fibrinogen value)+(0.894x IL-6 value)+(0.659x CRP value). Values for both models Exp(B)=4.882; P of sample=0.83; logit=-0.19; OR= 23.84; model accuracy for the first model 87% and for the second 88%; Omnibus test of the first model c2=34.324; p=0.000; reliability coefficient -2LogLH=56.854; Omnibus test of the second model c2=39.774; p=0.000; and -2LogLH=51.403. Conclusions: The ageing of blood vessels in COVID-19 can be predicted.

Gray-Level Co-occurrence Matrix Analysis of Nuclear Textural Patterns in Laryngeal Squamous Cell Carcinoma: Focus on Artificial Intelligence Methods.

Gray-level co-occurrence matrix (GLCM) and discrete wavelet transform (DWT) analyses are two contemporary computational methods that can identify discrete changes in cell and tissue textural features. Previous research has indicated that these methods may be applicable in the pathology for identification and classification of various types of cancers. In this study, we present findings that squamous epithelial cells in laryngeal carcinoma, which appear morphologically intact during conventional pathohistological evaluation, have distinct nuclear GLCM and DWT features. The average values of nuclear GLCM indicators of these cells, such as angular second moment, inverse difference moment, and textural contrast, substantially differ when compared to those in noncancerous tissue. In this work, we also propose machine learning models based on random forests and support vector machine that can be successfully trained to separate the cells using GLCM and DWT quantifiers as input data. We show that, based on a limited cell sample, these models have relatively good classification accuracy and discriminatory power, which makes them suitable candidates for future development of AI-based sensors potentially applicable in laryngeal carcinoma diagnostic protocols.

Reconstruction of Moderately and Severely Atrophic Scalp-A Multicentric Experience in Surgical Treatment of Patients Irradiated for Tinea Capitis in Childhood and Surgical Algorithm.

Background and Objectives: Before the introduction of griseofluvin, the use of X-ray radiation was the treatment of choice for tinea capitis. More than half a century later various types of tumors have been found to be associated with childhood irradiation due to tinea capitis, most commonly cancers of the head and neck, as well as brain tumors. The often unusually aggressive and recurrent nature of these tumors necessitates the need for repeated surgeries, while the atrophic skin with an impaired vascular supply due to radiation often poses an additional challenge for defect reconstruction. We present our experience in the surgical treatment of such patients. Materials and Methods: This is a retrospective cohort study. In this study, 37 patients treated for acquired defects of the scalp with a history of irradiation therapy due to tinea capitis in childhood were included in this study, 24 male and 13 female patients. The mean age at the first appointment was 60.6 ± 7.8, with the youngest included patient being 46 and the oldest being 75 years old. Patients' characteristics, surgical treatment, and complications were analyzed and a reconstructive algorithm was developed. Results: Local flaps were used for reconstruction in 34 patients, direct sutures were used in 10 patients and 20 patients received split-thickness skin grafts for coverage of both primary and secondary defects for reconstruction of flap donor sites. One regional flap and one dermal substitute covered by an autologous skin graft were also used for reconstruction. Complications occurred in 43.2% of patients and were significantly associated with the presence of comorbidities (p = 0.001), aseptic bone necrosis (p = 0.001), as well as skin atrophy in frontal, occipital, and parietal region (p = 0.001, p = 0.042 and p = 0.001, respectively). A significant correlation between major complications and moderate skin atrophy was found only in the parietal region (p = 0.026). Conclusions: Unfortunately, many protocols developed for scalp reconstruction are not applicable in the setting of severe or diffuse scalp skin atrophy associated with high tumor recurrence rate and radiation-induced vascular impairment, such as in tinea capitis patients in Serbia. An algorithm has been developed based on the authors' experience in managing these patients.

Ramsay Hunt Syndrome with Pharyngolaryngeal Involvement Mimicking Acute Stroke: A Case Report.

Ramsay Hunt syndrome is a clinical manifestation of the reactivation of latent varicella zoster virus in the geniculate ganglion after acute infection. It is commonly associated with an acute peripheral facial nerve paralysis, auricular vesicular eruption and acute sensorineural hearing loss. However, in some rare cases the involvement of other cranial nerves, especially the glossopharyngeal and vagal is described. We present a 56-year-old male patient who was diagnosed with acute pharyngitis. Two days later, the patient developed dysarthria, hoarseness, and left side facial weakness. Considering a patient's history of cardiovascular events, the acute stroke was suspected. Magnetic resonance imaging ruled out an acute cerebrovascular accident. The patient's otalgia aggravated and he reported hearing loss. Clinical examination revealed facial paralysis affecting the left side of the face, erythematous rash on the left auricle, multiple vesicles present on patient's left tympanic membrane, ulcerous lesion on the left side of the soft palate and ipsilateral velopharyngeal palsy. Indirect laryngoscopy revealed ulcerous lesions in the left side of the epiglottis and left vocal cord paralysis. The patient was diagnosed with Ramsay Hunt syndrome with cranial polyneuropathy. Oral acyclovir and oral prednisolone were administered. Seven months after discharge, facial paralysis improved to lower grade and flexible laryngoscopy showed that the left vocal cord had resumed normal movement. Ramsay Hunt syndrome can be accompanied by involvement of other cranial nerves. Previous history of hypertensive crises and myocardial infarction may influence a diagnosis of Ramsay Hunt syndrome, especially when it has atypical presentation. However, this diagnosis should be considered in patients with unilateral multiple cranial nerve palsies.

COVID-19 and Cutaneous Squamous Cell Carcinoma-Impact of the Pandemic on Unequal Access to Healthcare.

Most skin tumors are not fatal, but if not treated in a timely manner, they can lead to significant morbidity. Due to the COVID-19 pandemic and in order to create more capacities for the treatment of COVID-19-positive patients as well as to contain the spread of the virus, the healthcare system was reorganized worldwide, leading to decreased access to preventive screening programs. The aim of this study was to evaluate the impact of the pandemic on healthcare accessibility to cutaneous squamous cell carcinoma patients in Serbia. This retrospective study was conducted at the Clinic for Burns, Plastic, and Reconstructive Surgery, University Clinical Center of Serbia in Belgrade. Patient demographics and pathohistological findings of tumors of patients living in and outside the capital in the period before, during, and after the pandemic were compared. The two groups did not show any differences regarding the largest tumor diameter prior and during the pandemic; however, this difference became extremely noticeable after the pandemic (15 mm vs. 27 mm; p < 0.001). While cSCCs are commonly slow-growing tumors, the impact of the COVID-19 pandemic is not negligible. This study found a population at a significant risk of cSCC metastasis, with additional evidence likely to emerge in the upcoming years.

Indirect laryngeal surgery of vocal fold polyps: a dying or evolving art?

Objective: Vocal fold polyps (VFPs) are the most common benign laryngeal lesions that require surgery and are routinely managed by microlaryngoscopy (MLS) under general anaesthesia. Prior to introduction of MLS, VFPs were removed using indirect laryngoscopic surgery (ILS) in local anaesthesia, a procedure that required substantial surgical skill to operate with an unmagnified mirror view of the larynx. With the adoption of wireless endoscopy equipment and personal computers, we tried to simplify this technique so that it can be easily performed in the office. This study aimed to assess the effectiveness of ILS by comparing voice outcomes with MLS. Materials and methods: ILS and MLS were performed in six patients each. Treatment outcomes were measured using a voice self-assessment and objective acoustic analysis. The total cost of both procedures was calculated. Results: Both techniques allowed successful removal of VFPs in all patients, without significant intergroup differences in voice outcomes. The cost of ILS was significantly lower. Conclusions: Despite the pilot nature of the study and the small sample size, our data indicate the potential value of this technique which, considering its simplicity and economic value could be used as an alternative to MLS in carefully selected patients.

Electrochemical and theoretical study on interaction between erlotinib and DNA.

A comprehensive investigation of tyrosine kinase inhibitor erlotinib (ERL) electrochemical behavior and interaction with DNA was performed with the aim to clarify its redox mechanism and to determine the mode of binding. Irreversible oxidation and reduction processes of ERL on glassy carbon electrode were investigated using three voltammetric techniques CV, DPV, SWV in pH range between 2.0 and 9.0. Oxidation was established as an adsorption-controlled process, while the reduction manifested diffusion-adsorption mixed controlled process in acidic medium and adsorption became predominant in the neutral solutions. According to the determined number of transferred electrons and protons, oxidation and reduction mechanism of ERL are proposed. To follow the interaction between ERL and DNA, the multilayer ct-DNA electrochemical biosensor was incubated in ERL solutions concentrations ranged from 2 × 10-7 M to 5 × 10-5 M (pH 4.6) for 30 min. SWV measurements have shown the decrease in deoxyadenosine peak current as a consequence of ERL increased concentration and binding to ct-DNA. The calculated value of binding constant was K = 8.25 × 104 M-1. Molecular docking showed that ERL forms hydrophobic interactions when docked into minor groove, as well as when intercalated, and molecular dynamics analysis predicted the stability of obtained complexes. These results together with voltammetric studies imply that the intercalation could be more dominant way ERL binding to DNA compared to minor groove binding.

Effects of successful parathyroidectomy on neuropsychological and cognitive status in patients with asymptomatic primary hyperparathyroidism.

PURPOSE: Besides typical clinical symptoms, primary hyperparathyroidism (pHPT) is associated with impaired quality of life and cognitive status. The aim of this study was to evaluate the quality of life and cognitive impairment in patients with pHPT, before and after parathyroidectomy. METHODS: We conducted a panel study, which included asymptomatic pHPT patients scheduled for parathyroidectomy. Besides demographic and clinical data, patients' quality of life and cognitive capacity were recorded before, 1 month, and 6 months following parathyroidectomy using the Short Form 36 questionnaire (RAND-36), Beck Depression Inventory (BDI), Depression Anxiety Stress Scales (DASS), Mini-Mental State Examination (MMSE), and Symptom Check List 90-revised version (SCL90R). RESULTS: During a 2-year follow-up, 101 patients entered the study (88 women), with an average age of 60.7 years. The Global score of RAND-36 test ameliorated by almost 50% 6 months after parathyroidectomy. The most sustained subscores of the RAND-36 test were role functioning/physical and health change, with an improvement of more than 125%. According to the BDI, DASS depression subscore, and SCL90R depression subscore, the extent of depressive symptoms reduction was approximately 60% 6 months postoperatively. The level of anxiety was reduced by 62.4%, measured by both the DASS and SCL90R anxiety subscores. The stress level was almost halved according to the DASS stress subscore (from 10.7 to 5.6 points). The results of the MMSE test showed a significant improvement postoperatively, for 1.2 points (4.4%). A worse preoperative score of each tool was related to the higher magnitude of improvement 6 months after parathyroidectomy. CONCLUSION: A considerable number of pHPT patients, even without other typical symptoms, show signs of impaired quality of life and neurocognitive status preoperatively. After a successful parathyroidectomy, there is an improvement in quality of life, declined levels of depression, anxiety, and stress, as well as amelioration of cognitive status. Patients with more impaired quality of life and pronounced neurocognitive symptoms may expect more benefits from the surgery.

Buffered Versus Nonbuffered Local Anesthetics and Local Pain Scores in Upper Eyelid Blepharoplasty: Randomized Controlled Trial.

PURPOSE: This split-face study aimed to see whether different types of local anesthetics or their buffered/nonbuffered combinations produce lower pain scores in upper eyelid blepharoplasty. METHODS: The study involved 288 patients, randomly divided into 9 groups: 1) 2% lidocaine with epinephrine-Lid + Epi; 2) 2% lidocaine with epinephrine and 0.5% bupivacaine (1:1)-Lid + Epi + Bupi; 3) 2% lidocaine with 0.5% bupivacaine (1:1)-Lid + Bupi; 4) 0.5% bupivacaine-Bupi; 5) 2% lidocaine-Lid; 6) 4% articaine hydrochloride with epinephrine-Art + Epi; 7) buffered 2% lidocaine/epinephrine with sodium bicarbonate (SB) in a 3:1 ratio-Lid + Epi + SB; 8) buffered 2% lidocaine with SB in a 3:1 ratio-Lid + SB; 9) buffered 4% articaine hydrochloride/epinephrine with SB in a 3:1 ratio-Art + Epi + SB. Following the injection of the first eyelid and a 5-minute period of soft pressure on the injection site, patients were asked to rate their pain level on the Wong-Baker Face Pain Rating Visual Analogue Scale. Rating of the pain level was repeated 15 and 30 minutes following anesthetic administration. RESULTS: The lowest pain scores at the first time point were observed in Lid + SB when compared with all of the other groups ( p < 0.05). At the final time point, significantly lower scores were also observed in Lid + SB, Lid + Epi + SB, and Art + Epi + SB when compared with the Lid + Epi group ( p < 0.05). CONCLUSION: These findings could help surgeons select an appropriate combination of local anesthetics, particularly in patients with lower pain threshold and tolerance because buffered combinations of local anesthetics produce significantly lower pain scores compared with nonbuffered solutions.

Emergency Tracheostomy Due to a Myasthenic Crisis in a Post-COVID Patient: Report of a Case.

Myasthenia gravis is an autoimmune disorder caused by the production of antibodies that block either acetylcholine receptors or structural receptors of the neuromuscular junction. There is expanding evidence that novel coronavirus (2019-nCoV) disease can lead to the development of an autoimmune response. Myasthenic crisis, a life-threatening respiratory muscle weakness severe enough to necessitate intubation or tracheostomy, can be a potential complication of myasthenia gravis. In this report, we describe the case of a 57-year-old man with acute respiratory insufficiency requiring emergency tracheostomy. His health condition rapidly deteriorated 1 week after initiating systemic corticosteroid treatment for a suspected adult-onset asthma exacerbation. The patient had a history of COVID-19 infection and thymectomy, which were noted in his medical records. Serological testing and electrodiagnostic evaluation confirmed the diagnosis of myasthenia gravis. The patient was treated with plasma exchange, continuous neostigmine infusion, and prednisone. He was successfully decannulated and discharged with anticholinesterase inhibitors and long-term immunosuppression therapy. It is important to consider neurological disorders in the differential diagnosis for patients presenting with respiratory insufficiency, particularly during the COVID-19 pandemic.

Necrotizing Skin and Soft Tissue Infection after Gluteal Augmentation in a Perioperatively Asymptomatic COVID-19 Patient-Complications of the Post-Lockdown Era? A Case Report.

Introduction: Aesthetic surgery procedures are generally done in a relatively healthy population and carry a rather low risk compared to other surgical specialties. The incidence of complications in aesthetic surgery varies greatly depending on the type, wound cleanliness regarding the anatomical site, complexity of the surgery, patient's age, and comorbidities but is generally considered low. The overall incidence of surgical site infections (SSIs) in all aesthetic surgical procedures is around 1% in most of the literature while cases of necrotizing soft tissue infections are mostly found as individual reports. In contrast, treating COVID-19 patients is still challenging with many diverse outcomes. Surgical stress and general anesthesia are known mediators of cellular immunity impairment while studies regarding COVID-19 infection unquestionably have shown the deterioration of adaptive immunity by SARS-CoV-2. Adding COVID-19 to the modern surgical equation raises the question of immunocompetence in surgical patients. The main question of the modern post-lockdown world is: what could be expected in the postoperative period of perioperatively asymptomatic COVID-19 patients after aesthetic surgery? Case report: Here, we present a purulent, complicated, necrotizing skin and soft tissue infection (NSTI) after gluteal augmentation most likely triggered by SARS-CoV-2-induced immunosuppression followed by progressive COVID-19 pneumonia in an otherwise healthy, young patient. To the best of our knowledge, this is the first report of such adverse events in aesthetic surgery related to COVID-19. Conclusion: Aesthetic surgery in patients during the incubation period of COVID-19 or in asymptomatic patients could pose a significant risk for surgical complications, including severe systemic infections and implant loss as well as severe pulmonary and other COVID-19-associated complications.

Metformin promotes antitumor activity of NK cells via overexpression of miRNA-150 and miRNA-155.

OBJECTIVES: Metformin, an oral anti-diabetic drug, is known to possess a powerful antitumor effect by modulating the tumor-immune interaction. The precise influence of metformin on natural killer (NK) cells, a crucial innate immunity player, is not completely understood. In our study, analyses of the effect of metformin on the NK cell functional phenotype were performed, and the potential mechanisms underlying it were investigated. METHODS: BALB/C wild type mice were treated with metformin, and the functional phenotype of splenocytes and potential underlying mechanisms were investigated. RESULTS: Metformin significantly boosts NK cell cytotoxicity and the percentage of NKp46+, FasL+, and interferon (IFN)-γ+ NK cells while decreasing interleukin (IL)-10 producing NK cells. Our research also demonstrated that the simultaneous administration of metformin and 1-methyl-DL-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase (IDO), significantly increased the NK cells synthesis of IFN-γ, IL-17, perforin, and FasL and NKp46 expression. These findings imply that metformin potentiates NK cell cytotoxicity through mechanisms other than IDO blockade. Metformin administration strongly increased the expression of immunostimulatory microRNA (miRNA)-150 and miRNA-155, while decreasing the expression of immunosuppressive miRNA-146a. CONCLUSIONS: These findings suggest that metformin can directly potentiate NK cell activation and cytotoxicity. This research may contribute to dissecting key mechanisms of metformin exerting antitumor activity to advance the use of metformin as an antitumor agent.