High Level Of Efficacy Research Articles

Typhoid fever control in the 21st century: where are we now?

Momentum for achieving widespread control of typhoid fever has been growing over the past decade. Typhoid conjugate vaccines represent a potentially effective tool to reduce the burden of disease in the foreseeable future and new data have recently emerged to better frame their use-case. We describe how antibiotic resistance continues to pose a major challenge in the treatment of typhoid fever, as exemplified by the emergence of azithromycin resistance and the spread of Salmonella Typhi strains resistant to third-generation cephalosporins. We review efficacy and effectiveness data for TCVs, which have been shown to have high-level efficacy (≥80%) against typhoid fever in diverse field settings. Data from randomized controlled trials and observational studies of TCVs are reviewed herein. Finally, we review data from multicountry blood culture surveillance studies that have provided granular insights into typhoid fever epidemiology. These data are becoming increasingly important as countries decide how best to introduce TCVs into routine immunization schedules and determine the optimal delivery strategy. Continued advocacy is needed to address the ongoing challenge of typhoid fever to improve child health and tackle the rising challenge of antimicrobial resistance.

Safety and immunogenicity following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a secondary analysis of a randomised, placebo-controlled, phase 2 trial

BackgroundEmerging SARS-CoV-2 variants and evidence of waning vaccine efficacy present substantial obstacles towards controlling the COVID-19 pandemic. Booster doses of SARS-CoV-2 vaccines might address these concerns by amplifying and broadening the immune responses seen with initial vaccination regimens. We aimed to assess the immunogenicity and safety of a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373).MethodsThis secondary analysis of a phase 2, randomised study assessed a single booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-M adjuvant (NVX-CoV2373) in healthy adults aged 18–84 years, recruited from 17 clinical centres in the USA and Australia. Eligible participants had a BMI of 17–35 kg/m2 and, for women, were heterosexually inactive or using contraception. Participants who had a history of SARS-CoV or SARS-CoV-2, confirmed diagnosis of COVID-19, serious chronic medical conditions, or were pregnant or breastfeeding were excluded. Approximately 6 months following their primary two-dose vaccination series (administered day 0 and day 21), participants who received placebo for their primary vaccination series received a placebo booster (group A) and participants who received NVX-CoV2373 for their primary vaccination series (group B) were randomly assigned (1:1) again, via centralised interactive response technology system, to receive either placebo (group B1) or a single booster dose of NVX-CoV2373 (5 μg SARS-CoV-2 rS with 50 μg Matrix-M adjuvant; group B2) via intramuscular injection; randomisation was stratified by age and study site. Vaccinations were administered by designated site personnel who were masked to treatment assignment, and participants and other site staff were also masked. Administration personnel also assessed the outcome. The primary endpoints are safety (unsolicited adverse events) and reactogenicity (solicited local and systemic) events and immunogenicity (serum IgG antibody concentrations for the SARS-CoV-2 rS protein antigen) assessed 14 days after the primary vaccination series (day 35) and 28 days following booster (day 217). Safety was analysed in all participants in groups A, B1, and B2, according to the treatment received; immunogenicity was analysed in the per-protocol population (ie, participants in groups A, B1, and B2) who received all assigned doses and who did not test SARS-CoV-2-positive or received an authorised vaccine, analysed according to treatment assignment). This trial is registered with ClinicalTrials.gov, NCT04368988.Findings1610 participants were screened from Aug 24, 2020, to Sept 25, 2020. 1282 participants were enrolled, of whom 173 were assigned again to placebo (group A), 106 were re-randomised to NVX-CoV2373–placebo (group B1), and 104 were re-randomised to NVX-CoV2373–NVX-CoV2373 (group B2); after accounting for exclusions and incorrect administration, 172 participants in group A, 102 in group B1, and 105 in group B2 were analysed for safety. Following the active booster, the proportion of participants with available data reporting local (80 [82%] of 97 participants had any adverse event; 13 [13%] had a grade ≥3 event) and systemic (75 [77%] of 98 participants had any adverse event; 15 [15%] had a grade ≥3 event) reactions was higher than after primary vaccination (175 [70%] of 250 participants had any local adverse event, 13 [5%] had a grade ≥3 event; 132 [53%] of 250 had any systemic adverse event, 14 [6%] had a grade ≥3 event). Local and systemic events were transient in nature (median duration 1·0–2·5 days). In the per-protocol immunogenicity population at day 217 (167 participants in group A, 101 participants in group B1, 101 participants in group B2), IgG geometric mean titres (GMT) had increased by 4·7-fold and MN50 GMT by 4·1-fold for the ancestral SARS-CoV-2 strain compared with the day 35 titres.InterpretationAdministration of a booster dose of NVX-CoV2373 resulted in an incremental increase in reactogenicity. For both the prototype strain and all variants evaluated, immune responses following the booster were similar to or higher than those associated with high levels of efficacy in phase 3 studies of the vaccine. These data support the use of NVX-CoV2373 in booster programmes.FundingNovavax and the Coalition for Epidemic Preparedness Innovations.

A SOX2-engineered epigenetic silencer factor represses the glioblastoma genetic program and restrains tumor development.

Current therapies remain unsatisfactory in preventing the recurrence of glioblastoma multiforme (GBM), which leads to poor patient survival. By rational engineering of the transcription factor SOX2, a key promoter of GBM malignancy, together with the Kruppel-associated box and DNA methyltransferase3A/L catalytic domains, we generated a synthetic repressor named SOX2 epigenetic silencer (SES), which induces the transcriptional silencing of its original targets. By doing so, SES kills both glioma cell lines and patient-derived cancer stem cells in vitro and in vivo. SES expression, through local viral delivery in mouse xenografts, induces strong regression of human tumors and survival rescue. Conversely, SES is not harmful to neurons and glia, also thanks to a minimal promoter that restricts its expression in mitotically active cells, rarely present in the brain parenchyma. Collectively, SES produces a significant silencing of a large fraction of the SOX2 transcriptional network, achieving high levels of efficacy in repressing aggressive brain tumors.

How to Implement the 3-Phase FODMAP Diet Into Gastroenterological Practice.

Background/AimsThe 3-phase fermentable oligo-, di-, mono-saccharides, and polyols (FODMAP) diet has shown a high level of efficacy in irritable bowel syndrome, largely based on dietitian delivered education. However, access to dietitians can be limited, and challenges exist when applying the diet to a wide range of cultures, such as limited FODMAP analysis of local foods. This review aims to discuss ways to optimally use the FODMAP diet in practice in a wide range of cultures, directed at gastroenterologists from a dietitian’s perspective.MethodsRecent literature was analysed via search databases including Medline, CINAHL, PubMed and Scopus.ResultsThe dietetic process involves detailed assessment and follow-up through the 3 stages of the FODMAP diet (restriction, re-introduction, and long-term maintenance). Emerging evidence suggests the diet can be delivered by other health professionals such as the gastroenterologist or nurse, but training on how to do so successfully would be needed. Self-guided approaches through use of technology or specialised food delivery services may be an alternative when dietitians are not available, but efficacy data is limited. Regardless of delivery mode, nutritional and psychological risks of the diet must be mitigated. Additionally, culturally appropriate education must be provided, with accommodations necessary when the FODMAP content of local foods are unknown.ConclusionWhile the diet has shown improved irritable bowel syndrome outcomes across studies, it is important to acknowledge the essential role of dietitians in implementing, tailoring, and managing the diet to achieve the best outcome for each individual.

Open-Label Study to Evaluate the Efficacy of a Topical Anhydrous Formulation with 15% Pure Ascorbic Acid and Ginger as a Potent Antioxidant

Vitamin C is one of the naturally occurring antioxidants capable of reducing or preventing skin photoaging. Achieving a stable formulation with the optimal dose of ascorbic acid to ensure a biologically significant antioxidant effect is a challenge when developing cosmetic formulations. The objective of this study was to develop a stable formula in a non-aqueous media with 15% pure vitamin C supplemented with ginger and to study its efficacy, skin tolerance, and cosmetic assessment in 33 women. Vitamin C stability over time was determined via a high-performance liquid chromatography (HPLC) technique versus an aqueous option. Reactive oxygen species (ROS) determination was quantified to provide antioxidant effect. A 56-day in vivo study was performed to evaluate skin luminosity and hyperpigmentation reduction. Skin acceptability was verified by a dermatologist. The HPLC studies demonstrated a high stability of the anhydrous formula compared to an aqueous option. The in vitro studies showed a reduction in ROS of 93% (p-value < 0.0001). In vivo, luminosity increased by 17% (p-value < 0.0001) and skin tone became 10% more uniform (p-value < 0.007). Moreover, very good skin tolerance was determined as the dermatologist did not determine any clinical signs, and the subjects did not report any feelings of discomfort. We were able to develop an anhydrous formula of pure vitamin C that combines very good stability, consumer acceptance, and skin tolerance with a high level of efficacy.

READINESS AND EFFICACY OF MATHEMATICS TEACHERS ON BLENDED LEARNING IN THE NEW NORMAL

The study aimed to determine the levels of readiness and efficacy for blended learning and its relationship. Specifically, it ought to answer the following questions: 1. What is the level of readiness of Mathematics teachers on blended teaching in the new normal in terms of foundations, planning, instructional methods and strategies, evaluation and assessment, and management? 2. What is the level of efficacy of Mathematics teachers on blended teaching in the new normal in terms of: student engagement; instructional strategies; and classroom management? 3. Is there a significant relationship between the readiness and efficacy of Mathematics teachers on blended teaching in the new normal? The results for readiness indicated a high degree of preparedness for blended learning, which can verbally be interpreted into "High Level of Readiness." The results showed a high level of efficacy for blended learning, which is interpreted verbally as "Extremely Efficient." Furthermore, the results have shown significant relationship between the readiness and efficacy of secondary Mathematics teachers on blended learning. Therefore, the hypothesis stating that there is no significant relationship between the readiness and efficacy of secondary Mathematics teachers for blended learning was rejected. Based on the findings and conclusions of the study, it is recommended that the results be used as evidence and guide in the implementation and conduct of evaluations, trainings and interventions between and among the stakeholders of education in ensuring the continuity of learning amidst the current situation.

Career decision self-efficacy of Indonesian students

Early adulthood is one of the crucial moments of an individual’s life since it marks a person’s thinking seriously regarding the future, especially in careers. An individual will firstly make a series of career decisions before choosing a career. Self-efficacy is the best predictor of students’ academic and social integration. This study used a quantitative method with a descriptive analysis approach to describe and identify the status of career decision-making self-efficacy students in preparing for career decisions. Participants of the current study were 196 students from different backgrounds such as genders, choice of majors, domiciles, and types of accommodation. Participants were selected using a simple random sampling technique. The instrument used is Career Decision Self Efficacy. The findings revealed that 70.9 % of the students are in a high level of Career Decision Self Efficacy (M= 98.9), and there were no differences in Career Decision Self Efficacy among students reviewed based on genders, and choice of majors, domiciles, and types of accommodations.

Camrelizumab plus low-dose apatinib and SOX in the first-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma: A single-arm, dose-escalation and expansion study.

e16053 Background: The combination of camrelizumab, an anti-PD-1 monoclonal antibody, and apatinib, a selective VEGFR-2 inhibitor, has shown synergistic antitumor effects in G/GEJ adenocarcinoma patients. We aimed to evaluate the safety and efficacy of camrelizumab combined with low-dose apatinib and SOX in the first-line treatment of advanced G/GEJ adenocarcinoma. Methods: In this study (ChiCTR2000034109), eligible patients were diagnosed as unresectable or potentially resectable G/GEJ adenocarcinoma, HER2-negative or unknown HER2 status, and treatment-naive with inhibitors of VEGFR or PD-1/PD-L1. In dose escalation phase, 9 patients (3 in each group) were given with camrelizumab (200 mg, d1), apatinib (250 mg, qod/qd), and SOX regimen (oxaliplatin, 100/130 mg/m2, d1; S-1, 40 mg, bid, d1-14) every 3 weeks. Afterwards, the optimal combination integrated with safety and efficacy would be applied in dose expansion phase for another 33 patients. After up to 6-8 cycles of quadruple therapy, patients with complete response (CR)/partial response (PR)/stable disease (SD) would continue camrelizumab plus apatinib therapy until disease progression, intolerable toxicities, physician/patient withdrawal, or up to 2 years of camrelizumab therapy. The safety and efficacy were assessed by investigators per CTCAE v5.0 and RECIST v1.1, respectively. The primary endpoints were maximum tolerated dose and objective response rate (ORR). Results: From Jun 12, 2020 to Jul 26, 2021, no patient reported any dose-limiting toxicity in the dose escalation phase, thus another 11 eligible patients had been enrolled to receive quadruple therapy with apatinib (250 mg, qd) and oxaliplatin (130 mg/m2, d1). The patients were characterized with a median age of 59 years (range, 46-57), 30% GEJ adenocarcinoma, 100% lymph node metastasis, and 45% liver metastases. As of Nov 30, 2021, with a median follow-up of 10.9 months (range, 4.2-17.6), safety and efficacy were assessed in 19 evaluable patients, with overall response of 18 PR and 1 SD. Confirmed ORR and DCR were 94.7% (95% CI, 71.9%-99.7%) and 100% (95% CI, 79.1%-100%), respectively. The median PFS, median DOR and estimated 1-year OS rate were 8.3 months (95% CI, 6.1-10.5), 6.7 months (95% CI, 5.9-7.5) and 59.0%, respectively, with the median OS not reached yet. Conversion surgery had been conducted in 2/19 (10.5%) patients, with one case of pathological CR and one clinical CR. Grade 3-4 treatment-related adverse events occurred in 45% of patients, with rash ranking the most frequent. No new safety signal was identified. Conclusions: Camrelizumab combined with low-dose apatinib and SOX showed high level of safety and efficacy in the first-line treatment of advanced G/GEJ adenocarcinoma. Clinical trial information: ChiCTR2000034109.

Immune checkpoint inhibitors (ICIs) plus CAPOX in the treatment of unresectable advanced or recurrent biliary tract carcinoma (BTC): A retrospective study.

e16144 Background: Patients with advanced or unresectable BTC have limited treatment options and poor prognosis. The combination of ICIs with chemotherapy has demonstrated promising antitumor activity with manageable safety in the first- or second-line in treatment of patients with advanced or unresectable BTC, but only a subset of patients with BTC derive benefit. The standard systemic treatment for BTC has been gemcitabine (800-1250 mg/m2, i.v., d1 and d8, q3w) in combination with oxaliplatin/cisplatin. The regimen is associated with high frequency of intravenous injection or more hospital days. All above highlights the need for new combinations. Therefore, we conducted a retrospective trial to evaluate ICIs combined with CAPOX (more convenient dosing regimen) in patients with advanced or recurrent BTC who were treatment-naive or failed to previous treatment. Methods: In this study, eligible patients were diagnosed as unresectable advanced or recurrent BTC, therapy-naive or failed to previous treatment with chemotherapy, inhibitors of VEGFR or PD-1/PD-L1. In therapy phase, 28 patients were given with ICIs (dosage and mode of administration according to instructions, d1), oxaliplatin (130 mg/m2, i.v., d1), and capecitabine (1000mg/m2, po, bid, d1-14) every 3 weeks, until disease progression, intolerable toxicities, or physician/patient withdrawal. The safety and efficacy were assessed by investigators per CTCAE v5.0 and RECIST v1.1, respectively. The primary endpoint was progression-free survival (PFS), the secondly endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and adverse events (AEs). Results: From Dec 24, 2019 to Aug 6, 2021, 28 patients had been enrolled to receive therapy. The patients were characterized with a median age of 58 years (range 53-79), 75% intrahepatic cholangiocarcinoma (ICC) and 25% gallbladder cancer (GBC), 25% lymph node metastasis, 25% liver metastases, 54% with history of surgery, and 57% with therapy-native. As of Jan 23, 2022, with a median follow-up of 9.0 months (range, 2.1-23.4), safety and efficacy were assessed in 26 evaluable patients, with response of 12 PR and 6 SD. Confirmed ORR and disease control rate (DCR) were 46.2% (95% CI, 27.1%-66.2%) and 69.2% (95% CI, 48.1%-84.9%), respectively. The median PFS, median OS and median DOR were 6.1 months (95% CI, 4.9-7.3), 16.5 months (95% CI, 5.0-28.0) and 5.0 months (95% CI, 2.0-8.0), respectively. Grade 3-4 treatment-related adverse events occurred in 32.1% of patients, with thrombocytopenia and bone marrow depression ranking the most frequent. No new safety signal was identified. Conclusions: In this study, ICIs combined with CAPOX not only showed high level of safety and efficacy, but also provided convenience in the treatment of unresectable advanced or recurrent BTC.

COVID-19 vaccine effectiveness in patients with cancer: remaining vulnerabilities and uncertainties.

Patients with cancer are at an increased risk of serious complications and death from COVID-19, which is heightened by being aged 40 years or older, major medical comorbidities, poor performance status, the presence of haematological malignancies, and the receipt of immunosuppressive cancer therapies.1–3 Early pivotal randomised trials of COVID-19 vaccines showed their high level of safety and efficacy, but excluded individuals on immunosuppressive therapies, which includes most patients with cancer, leaving uncertainty about vaccine efficacy and safety in this setting.

Assessing an O-antigen deficient, live attenuated Salmonella Gallinarium strain that is DIVA compatible, environmentally safe, and protects chickens against fowl typhoid

The objective of the present study was to create a highly attenuated, safe Salmonella Gallinarium (SG) vaccine strain for chicken vaccination against fowl typhoid (FT) diseases. The SG vaccine strain (SGVS) consists of three virulence-related gene deletions, namely, lon, cpxR, and rfaL. The parent strain (SGPS) with Δlon ΔcpxR genotype was utilized as the host strain for in-frame rfaL gene deletion by lambda red recombination. The SGVS was highly attenuated with improved environmental safety by zero fecal contamination beyond seven days for both oral and intramuscular immunization routes. Upon inoculation into 1-month-old young chicken, no vaccine-induced adverse behaviors were observed and did not cause a chronic state of infection as the SG wild-type strain did. Immunization of chicken elicited both humoral and cell-mediated immune responses demarcated by, IgY antibody assessment, T-cell responses in peripheral blood mononuclear cells, and the induction of immunomodulatory cytokines, IFN-γ, IL-2, IL-12, and IL-4 to resemble both Th1 and Th2 type of immune responses. The immunological assessment revealed a high level of efficacy of the SGVS when inoculated via the IM route than the oral route. The strain was less cytotoxic with reduced cytotoxicity on chicken macrophages and was DIVA capable with minimum reactivity of immunized serum with purified SG lipopolysaccharides. The challenge study could generate 70% protection in chicken for SGVS, whereas no birds were protected in the PBS challenged group. The protection levels were evident in histopathological assessment of spleen and liver specimens and also the external appearance of the spleen with reduced lesions on immunized groups. Further experiments may be warranted to dose and route optimization for further increase in the protection level derived by present SGVS.

Role of Efficacy as a Determinant of Locomotor Activation by Mu Opioid Receptor Ligands in Female and Male Mice.

Mu opioid receptor (MOR) agonists produce locomotor hyperactivity in mice as one sign of opioid-induced motor disruption. The goal of this study was to evaluate the degree of MOR efficacy required to produce this hyperactivity. Full dose-effect curves were determined for locomotor activation produced in male and female Institute of Cancer Research (ICR) mice by (1) eight different single-molecule opioids with high to low MOR efficacy and (2) a series of fixed-proportion fentanyl/naltrexone mixtures with high to low fentanyl proportions. Data from the mixtures were used to quantify the efficacy requirement for MOR agonist-induced hyperactivity relative to efficacy requirements determined previously for other MOR agonist effects. Specifically, efficacy requirement was quantified as the EP50 value, which is the "Effective Proportion" of fentanyl in a fentanyl/naltrexone mixture that produces a maximal effect equal to 50% of the maximal effect of fentanyl alone. Maximal hyperactivity produced by each drug and mixture in the present study correlated with previously published data for maximal stimulation of GTPɣS binding in MOR-expressing Chinese hamster ovary cells as an in vitro measure of relative efficacy. Additionally, the EP50 value for hyperactivity induced by fentanyl/naltrexone mixtures indicated that opioid-induced hyperactivity in mice has a relatively high efficacy requirement in comparison with some other MOR agonist effects, and in particular is higher than the efficacy requirement for thermal antinociception in mice or fentanyl discrimination in rats. Taken together, these data show that MOR agonist-induced hyperactivity in mice is efficacy dependent and requires relatively high levels of MOR agonist efficacy for its full expression. SIGNIFICANCE STATEMENT: Mu opioid receptor (MOR) agonist-induced hyperlocomotion in mice is dependent on the MOR efficacy of the agonist and requires a relatively high degree of efficacy for its full expression.

Treatment of patients with cancer using PD‑1/PD‑L1 antibodies: Adverse effects and management strategies (Review).

In 2020, there were an estimated 19.3 million new cancer cases and close to 10 million cancer deaths worldwide. Cancer remains one of the leading causes of death. In recent years, with the continuous improvement of our understanding of tumor immunotherapy, immunotherapeutics, such as immune checkpoint inhibitors, have gradually become a hot spot for tumor treatment. Amongst these, programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) related inhibitors, such as nivolumab and pembrolizumab, atezolizumab, avelumab and durvalumab have been shown to exhibit a high level of efficacy in several types of tumors. It has been confirmed that these inhibitors play an important role in the anti-tumor process, significantly improving the survival rate of patients and delaying the progress of the underlying cancer. However, its method of therapeutic interference and potential for damaging the immune system has caused concern regarding its suitability. As these adverse effects are caused by an immune response to endogenous tissues, they are designated as immune-related adverse events (irAEs). In this review, the typical irAEs reported in recent years and the management strategies adopted are highlighted, to serve as a reference in assessing the clinical response to these adverse reactions.

COVID-19 and medical tourism intentions for Iran – a test of the risk perception attitude framework (RPAF)

Purpose This paper aims to examine whether medical tourism can be a frontrunner in terms of post-pandemic recovery for the industry Design/methodology/approach A mixed-method analysis of 17 interviews and 210 questionnaires involving medical tourists to Iran was applied. Findings Medical tourists perceived the risks posed by COVID-19 as a temporal one, and attitudes toward post pandemic visitation intentions remained strong. In addition, these tourists can mostly be classified into responsive individuals, who demonstrate not only high risk but also high efficacy levels to negotiate the threats posed by the pandemic. No gender differences were located between male and female medical tourists in terms of post-COVID-19 travel intentions to Iran. Originality/value This research extends the application of the risk perception attitude framework to a medical tourism context. Furthermore, medical tourists are uncovered as another segment of crisis-resistant tourists.

Low-dose intrauterine contraception is an innovative approach to the prevention of unwanted pregnancy

Long-acting reversible contraception (LARC) is recognized as a highly effective and convenient method for preventing unwanted pregnancy. However, in real clinical practice, the level of implementation of LARC remains relatively low, which, presumably, may be related to misconceptions about their contraceptive efficacy and side effects among health professionals and patients. One method of long-acting reversible contraception is the intrauterine device. Hormone-containing intrauterine systems are recognized as one of the most affordable contraceptive methods, characterized by a very low failure rate (less than 1%), which does not depend on the patient’s compliance. A review of the literature focuses on the efficacy and safety of a low-dose levonorgestrelcontaining intrauterine system containing 19.5 mg of levonorgestrel (LNG-IUD 12). We present data on the advantages of this intrauterine system in comparison with its counterparts. Analysis of the literature has shown that adherence to low-dose contraception is observed among women of reproductive age. The smaller diameter of the guide tube is associated with a more successful and less painful insertion of the device into the uterine cavity. This may be an obvious advantage for young, nulliparous women. In addition, the LNG-IUD has a predominantly local progestogenic effect on the endometrium, so there is a relatively low development of systemic effects. Despite its lower levonorgestrel content, the LNG IUD 12 (Kyleena LNG 19.5 mg, levonorge strel-releasing intrauterine system with an average LNG release of 12 µg/24 h in vivo over the first year of use) has a high level of contraceptive efficacy. Thus, LNG-IUD 12 is associated with a favorable efficacy and safety profile regardless of a woman’s age or parity, which has been confirmed by the results of clinical trials.

Trigeminal neuropathy after tozinameran vaccination against COVID-19 in postmicrovascular decompression for trigeminal neuralgia: illustrative case.

BACKGROUNDVaccines against coronavirus disease 2019 have a high level of efficacy and safety across all populations. However, numerous case series have been published on neurological disorders, including Bell’s palsy, Guillain-Barre syndrome, transverse myelitis, and multiple sclerosis. The authors presented a case of trigeminal neuropathy after coronavirus vaccination in a patient who had undergone microvascular decompression (MVD) for trigeminal neuralgia (TN).OBSERVATIONSA 77-year-old woman presented with acute trigeminal neuropathy after receiving a Pfizer-BioNtech vaccination (tozinameran) against severe acute respiratory syndrome coronavirus 2. The patient had undergone MVD for TN and the facial pain completely disappeared. One month later, she received the first injection of the tozinameran vaccine. Twelve hours after vaccination, she presented with numbness and pain induced by touching any place on the entire right face. No eruption was observed on her face. The serum herpes zoster virus antibodies were confirmed within the normal range. Magnetic resonance imaging revealed no abnormalities. The authors suspected a right trigeminal neuropathy after vaccination. Administration of carbamazepine and pregabalin improved TN but facial numbness persisted, especially in the mandibular division.LESSONSThe coronavirus is a possible etiology of secondary trigeminal neuropathy in the case of MVD for TN.

B7-H3 Specific CAR T Cells for the Naturally Occurring, Spontaneous Canine Sarcoma Model.

One obstacle for human solid tumor immunotherapy research is the lack of clinically relevant animal models. In this study, we sought to establish a chimeric antigen receptor (CAR) T-cell treatment model for naturally occurring canine sarcomas as a model for human CAR T-cell therapy. Canine CARs specific for B7-H3 were constructed using a single-chain variable fragment derived from the human B7-H3-specific antibody MGA271, which we confirmed to be cross-reactive with canine B7-H3. After refining activation, transduction, and expansion methods, we confirmed target killing in a tumor spheroid three-dimensional assay. We designed a B7-H3 canine CAR T-cell and achieved consistently high levels of transduction efficacy, expansion, and in vitro tumor killing. Safety of the CAR T cells were confirmed in two purposely bred healthy canine subjects following lymphodepletion by cyclophosphamide and fludarabine. Immune response, clinical parameters, and manifestation were closely monitored after treatments and were shown to resemble that of humans. No severe adverse events were observed. In summary, we demonstrated that similar to human cancers, B7-H3 can serve as a target for canine solid tumors. We successfully generated highly functional canine B7-H3-specific CAR T-cell products using a production protocol that closely models human CAR T-cell production procedure. The treatment regimen that we designed was confirmed to be safe in vivo. Our research provides a promising direction to establish in vitro and in vivo models for immunotherapy for canine and human solid tumor treatment.

BYL719 (alpelisib) for the treatment of PIK3CA-mutated, recurrent/advanced cervical cancer.

Advanced/recurrent cervical cancer has limited therapeutic options, with a median progression-free survival after the failure of systemic treatments ranging between 3.5 and 4.5 months. Here, we reported our preliminary experience in the use of BYL719 (alpelisib) in advanced/recurrent cervical cancer after failure of at least 2 lines of treatment. The Istituto Nazionale dei Tumori di Milano approved this investigation. From April 2020 to September 2020, 17 consecutive patients with recurrent cervical cancer had Next Generation Sequencing (NGS). Of these, six patients harboring the PIK3CA mutation were included in the study. All patients had been treated with at least 2 previous lines of systemic treatment: 3 patients received >2 prior lines of treatment in the recurrent or metastatic setting; 60% had received prior bevacizumab in combination with chemotherapy. All patients started alpelisib at the daily dosage of 300 mg. Investigator-assessed confirmed objective response rate (ORR) was 33%. The disease control rate (DCR) was 100%. According to RECIST 1.1, two patients had a partial response (PR), and four patients had stable disease (SD). No complete response was observed. The mean duration of response (DOR) was 11.5 (SD 3.75) months; five patients had PR lasting for >9 months. One patient stopped the treatment at 0.82 months due to the onset of a grade 2 adverse event (AE) (skin rash). Grade 3 treatment-related AEs included: lymphoedema (n = 1, 17%) and rash (n = 1, 17%). No treatment-related grade 4-5 AEs occurred. Our preliminary data highlighted a high level of efficacy in this setting of patients. Further trials are needed to assess the safety and effectiveness of alpelisib in PIK3CA-mutated recurrent/advanced cervical cancer.

Simultaneous Nail and Skin Clearance in Ixekizumab Head-to-Head Trials for Moderate-to-Severe Psoriasis and Psoriatic Arthritis.

IntroductionThe lifetime incidence of nail psoriasis in patients with psoriasis is 80–90%, with 23–27% of patients having nail psoriasis at any given time. Nail psoriasis is even more prevalent in patients with comorbid psoriatic arthritis. Complete psoriasis clearance, an achievable therapeutic goal, should ideally include the resolution of nail psoriasis. Here, we assessed simultaneous skin and nail clearance in patients with psoriasis across five head-to-head trials comparing ixekizumab with other biologics.MethodsData were assessed in patients with moderate-to-severe psoriasis (with or without psoriatic arthritis) with nail psoriasis at baseline from the IXORA-R, IXORA-S, UNCOVER-2, UNCOVER-3, and SPIRIT-H2H trials. Ixekizumab patients received IXEQ2W to week 12 and IXEQ4W beyond week 12. PASI 100 depicted complete skin clearance, and PGA-F 0 (IXORA-R) or NAPSI 0 (all other trials) depicted complete nail clearance. Treatment comparisons were evaluated using the Cochran-Mantel-Haenszel test. Non-responder imputation was used for missing data.ResultsIxekizumab achieved significantly greater simultaneous skin and nail complete clearance than etanercept (UNCOVER-2: p < 0.001 and UNCOVER-3: p < 0.001) at week 12, demonstrating an efficacious and rapid response. Across all five head-to-head trials, ixekizumab achieved a high rate of simultaneous skin and nail clearance (range: 28.6–45.9% of patients) by week 24 that was maintained up to week 52 (range: 40.5–51.4% of patients). Ixekizumab achieved numerically greater simultaneous complete clearance than guselkumab at week 24 (p = 0.079), but statistically significant greater simultaneous clearance compared to ustekinumab (p < 0.001) and adalimumab (p = 0.006) at week 24 and week 52 (p < 0.001 and p = 0.007, respectively).ConclusionIn five head-to-head trials, ixekizumab-treated patients had higher rates of simultaneous complete skin and nail clearance compared to etanercept, guselkumab, ustekinumab, and adalimumab, thereby reinforcing ixekizumab’s ability to achieve high levels of efficacy in multiple domains of psoriatic disease.Trial registrationNCT01474512, NCT01597245, NCT01646177, NCT03573323, NCT02561806, and NCT03151551.

Biochemical Profile and Antimicrobial Activity of an Herbal-Based Formula and Its Potential Application in Cosmetic Industry

Microbial infections, and especially microbial resistance, are critical and actual problems that require targeted and efficient therapeutic intervention. Natural-based solutions are a viable alternative, at least for complementary therapy, due to few or no side effects and high safety and efficacy levels. The aim of this study was to demonstrate the potential use of a patented formula based on Achillea millefolium, Origanum vulgare, and Lychnis coronaria species as an antibacterial ingredient, mainly for skin and mucosal infections, in order to support its pharmaco-cosmetic application. The chemical composition of the formula was analyzed by HPLC and spectrophotometric methods. Furthermore, antioxidant and antimicrobial activity were evaluated. To determine the formula’s safety for topical application, it was used on a reconstructed human epidermal model. The formula showed inhibitory activity on both Gram-positive and Gram-negative bacteria, respectively, moderate inhibition on B. cereus, Kocuria kristinae, P. aeurginosa, S. enterica Typhimurium, methicillin-resistant and methicillin-sensible S. aureus, as well as high inhibition on S. epidermidis, Serratia marescens, and Streptococcus pyogenes. The developed product was biochemically characterized for its content in polyphenols, triterpenes, and polyphenol carboxylic acids. The formula was proven to have a nonirritant effect on the human epidermis and important antioxidant activity.