Exploring the dual effect of novel 1,4-diarylpyranopyrazoles as antiviral and anti-inflammatory for the management of SARS-CoV-2 and associated inflammatory symptoms.

COVID-19 and associated substantial inflammations continue to threaten humankind triggering death worldwide. So, the development of new effective antiviral and anti-inflammatory medications is a major scientific goal. Pyranopyrazoles have occupied a crucial position in medicinal chemistry because of their biological importance. Here, we report the design and synthesis of a series of sixteen pyranopyrazole derivatives substituted with two aryl groups at N-1 and C-4. The designed compounds are suggested to show dual activity to combat the emerging Coronaviruses and associated substantial inflammations. All compounds were evaluated for their in vitro antiviral activity and cytotoxicity against SARS-CoV infected Vero cells. As well, the in vitro assay of all derivatives against the SARS-CoV Mpro target was performed. Results revealed the potential of three pyranopyrazoles (22, 27, and 31) to potently inhibit the viral main protease with IC50 values of 2.01, 1.83, and 4.60 µM respectively compared with 12.85 and 82.17 µM for GC-376 and lopinavir. Additionally, in vivo anti-inflammatory testing for the most active compound 27 proved its ability to reduce levels of two cytokines (TNF-α and IL-6). Molecular docking and dynamics simulation revealed consistent results with the in vitro enzymatic assay and indicated the stability of the putative complex of 27 with SARS-CoV-2 Mpro. The assessment of metabolic stability and physicochemical properties of 27 have also been conducted. This investigation identified a set of metabolically stable pyranopyrazoles as effective anti-SARS-CoV-2 Mpro and suppressors of host cell cytokine release. We believe that the new compounds deserve further chemical optimization and evaluation for COVID-19 treatment.

Risk factors for complicated Mohs surgery in the South Sweden Mohs Cohort.

BACKGROUND: Mohs micrographic surgery (MMS) is a precise, tissue-sparing surgical technique that offers superior cure rates compared to traditional surgical excision. However, the degree of difficulty of MMS depends on many variables, and consequently, the number of surgical stages required for each case is quite unpredictable. OBJECTIVES: To identify risk factors for complicated MMS, defined as MMS requiring ≥3 stages. METHODS: In a cohort study design, data were prospectively collected from 612 patients that underwent MMS for basal cell carcinoma (BCC) at the Department of Dermatology, Skåne University Hospital, Lund, between 2009 and 2020. Univariate and multivariate logistic regression were used to estimate the risk of MMS requiring ≥3 stages. Due to the risk of multicollinearity between recurrent or incompletely excised BCC and previous treatments, a partially and a fully adjusted multivariate logistic regression model were constructed. RESULTS: In fully adjusted multivariate analyses, age (odds ratio (OR) 1.02; confidence interval (CI) 95% 1.00-1.04), previous cryotherapy (OR 2.3; CI 95% 1.1-4.8), and >1 previous surgery (OR 3.4; CI 95% 1.5-7.7) were significantly associated with risk of complicated MMS. Recurrent BCC was associated with the risk of complicated MMS in partially adjusted multivariate analyses, but not in the fully adjusted analyses. In this highly selected cohort, histopathological subtype, and tumour localization were not associated with the risk of complicated MMS. CONCLUSIONS: Older age and tumours previously treated with cryotherapy or multiple prior surgeries increased the risk of MMS requiring ≥3 stages. Whether recurrent BCC is an independent risk factor for complicated MMS needs further evaluation. Knowledge of these risk factors may ameliorate the planning of Mohs surgeries.

Design and Synthesis of Benzene Homologues Tethered with 1,2,4-Triazole and 1,3,4-Thiadiazole Motifs Revealing Dual MCF-7/HepG2 Cytotoxic Activity with Prominent Selectivity via Histone Demethylase LSD1 Inhibitory Effect.

In this study, an efficient multistep synthesis of novel aromatic tricyclic hybrids incorporating different biological active moieties, such as 1,3,4-thiadiazole and 1,2,4-triazole, was reported. These target scaffolds are characterized by having terminal lipophilic or hydrophilic parts, and their structures are confirmed by different spectroscopic methods. Further, the cytotoxic activities of the newly synthesized compounds were evaluated using in vitro MTT cytotoxicity screening assay against three different cell lines, including HepG-2, MCF-7, and HCT-116, compared with the reference drug Taxol. The results showed variable performance against cancer cell lines, exhibiting MCF-7 and HepG-2 selectivities by active analogs. Among these derivatives, 1,2,4-triazoles 11 and 13 and 1,3,4-thiadiazole 18 were found to be the most potent compounds against MCF-7 and HepG-2 cancer cells. Moreover, structure-activity relationship (SAR) studies led to the identification of some potent LSD1 inhibitors. The tested compounds showed good LSD1 inhibitory activities, with an IC50 range of 0.04-1.5 µM. Compounds 27, 23, and 22 were found to be the most active analogs with IC50 values of 0.046, 0.065, and 0.074 µM, respectively. In addition, they exhibited prominent selectivity against a MAO target with apparent cancer cell apoptosis, resulting in DNA fragmentation. This research provides some new aromatic-centered 1,2,4-triazole-3-thione and 1,3,4-thiadiazole analogs as highly effective anticancer agents with good LSD1 target selectivity.

Swimming through the sands of the Sahara and Arabian deserts: Phylogeny of sandfish skinks (Scincidae, Scincus) reveals a recent and rapid diversification.

Large parts of the Sahara Desert and Arabia are covered by sand seas and sand dunes, which are inhabited by specialized animal communities. For example, many lizards have developed adaptations to life in loose sand, including sand-swimming behavior. The best-known sand swimmers of the Saharo-Arabia are the sandfish skinks (genus Scincus). Although there are currently only four Scincus species recognized, their phylogenetic relationships have not yet been addressed in detail. We use eight genetic markers (three mitochondrial, five nuclear) and a complete sampling of species to infer the relationships within the genus. We employ multiple phylogenetic approaches to reconstruct the evolutionary history of these skinks and to assess the level of reticulation at the onset of their radiation. Our results indicate the presence of five strongly supported species-level lineages, four represented by the currently recognized species and the fifth by S. scincus conirostris, which does not form a clade with S. scincus. Based on these results we elevate the Iranian and northern Arabian S. conirostris to the species level. The two Saharan species, S. albifasciatus and S. scincus, are sister in all analyses. Deeper relationships within the genus, however, remained largely unresolved despite the extensive genetic data set. This basal polytomy, together with the fact that we detected no sign of hybridization in the history of the genus, indicates that the diversification of the five Scincus species was rapid, burst-like, and not followed by secondary hybridization events. Divergence time estimations show a Middle Pliocene crown radiation of the genus (3.3 Mya). We hypothesize that the aridification of the Saharo-Arabia that began in the Late Miocene triggered the initial diversification of Scincus, and that the subsequent expansion of sand deserts enabled their dispersal over the large Saharan and Arabian range. We discuss the evolution of body form in sand swimming lizards and ponder how Scincus retained their fully limbed morphology despite being sand swimmers that are typically limbless.

Design of molecular hybrids of phthalimide-triazole agents with potent selective MCF-7/HepG2 cytotoxicity: Synthesis, EGFR inhibitory effect, and metabolic stability.

This study reports an efficient and convenient click chemistry synthesis of a novel series of phthalimide scaffold linked to 1,2,3 triazole ring and terminal lipophilic fragments. Structures of newly synthesized compounds were well characterized by different spectroscopic tools. In vitro MTT cytotoxicity assay was performed comparing the cytotoxic effects of newly synthesized compounds to staurosporine using three different types: human liver cancer cell line (HepG2), Michigan cancer foundation-7 (MCF-7) and human colorectal carcinoma cell line (HCT116). The initial screening showed excellent to moderate anticancer activity for these newly synthesized compounds with high degree of cell line selectivity with micromolar (µM) half maximal inhibitory concentration (IC50) values against tumor cells. The SAR analysis of these derivatives confirmed the role of molecular fragments including phthalimide, linker, triazole, and terminal tails in correlation to activity. In addition, enzymatic inhibitory assay against wild type EGFR was performed for the most active compounds to get more details about their mechanism of action. In order to further explore their binding affinities, molecular docking simulation was studied against EGFR site. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated. One of the most prominent analogs is (6f) with terminal disubstituted ring and amide linker showed selective MCF-7 cytotoxicity profile with IC50 0.22 µM and 79 nM to EGFR target. Extensive structure activity relationship (SAR) analyses were also carried out. The pharmacokinetic profile of (6f) was studied showing good metabolic stability and long duration behavior. This design offered a potent selective anticancer phthalimide-triazole leads for further optimization in cancer drug discovery.

Variability in the diagnosis of surgical-site infections after full-thickness skin grafting: an international survey.

BACKGROUND: Diagnosis of a surgical-site infection (SSI) in dermatological surgery can be based entirely on a subjective assessment, according to the fourth criterion of the most common definition of an SSI, which was established by the US Centers for Disease Control and Prevention. OBJECTIVES: To investigate the interobserver agreement between dermatologists in their diagnosis of SSI of dermatosurgical wounds. METHODS: An international electronic photographic survey with eight photographs of wounds 1 week after full-thickness skin grafting (FTSG) was sent to dermatologists. All wounds were assessed in terms of visual criteria beforehand. Data collected from respondents included physician characteristics and experience, and SSI assessments of all wounds. RESULTS: In total, 393 dermatologists from 27 countries enrolled. Most respondents were from the U.S.A. (25%), followed by Sweden (24%) and the U.K. (13%). There was only a slight interobserver agreement on SSI suspicion (κ = 0·19). SSI suspicion was lower for male physicians (P = 0·03), board-certified dermatologists (P = 0·001), physicians regularly assessing surgical wounds (P = 0·03) and physicians performing FTSG (P < 0·001). Swedish physicians diagnosed more SSIs than U.S. physicians (P = 0·002). Erythema was more common in cases with higher SSI suspicion. CONCLUSIONS: This study reveals broad inter-rater variability in the diagnosis of SSI, illustrating the need for novel objective diagnostic methods that can better capture the variables that constitute an SSI.

Design, synthesis, molecular docking of new lipophilic acetamide derivatives affording potential anticancer and antimicrobial agents.

Fifteen new substituted N-2-(2-oxo-3-phenylquinoxalin-1(2H)-yl) acetamides 5a-f, 6a-f, and 8a-c were synthesized by reacting ethyl 2-(2-oxo-3-phenylquinoxalin-1(2H)-yl)acetate with various primary amines including benzylamines, sulfonamides, and amino acids. The in vitro antimicrobial screening of the target compounds was screened to assess their antibacterial and antifungal activity. As a result, seven compounds namely; 5a, 5c, 5d, 6a, 6c, 8b and 8c showed a promising broad spectrum antibacterial activity against both Gram-positive and Gram-negative strains. Among these, the analogs 5c and 6d were nearly as equiactive as ciprofloxacin drug. Meanwhile, four compounds namely; 5c, 6a, 6f and 8c exhibited appreciable antifungal activity with MIC values range 33-40 mg/mL comparable with clotrimazole (MIC 25 mg/mL). In addition, the anticancer effects of the synthesized compounds were evaluated against three cancer lines. The data obtained revealed the benzylamines and sulpha derivatives were the most active compounds especially 5f and 6f ones. Further EGFR enzymatic investigation was carried out for these most active compounds 5f and 6f resulting in inhibitory activity by 1.89 and 2.05 µM respectively. Docking simulation was performed as a trial to study the mechanisms and binding modes of these compounds toward the enzyme target, EGFR protein kinase enzyme. The results revealed good compounds placement in the active sites and stable interactions similar to the co-crystallized reference ligand. Collectively, the analogs 5f and 6f could be further utilized and optimized as good cytotoxic agents.

l-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents.

OBJECTIVE: High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have a role in appetite regulation and satiety. We investigated the effects of l-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. METHODS: We investigated the effects of the aromatic amino-acid and calcium-sensing receptor (CaSR) agonist l-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal (GI) hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo. We also examined the effect of oral l-Phe administration on glucose tolerance in rats. RESULTS: Oral administration of l-Phe acutely reduced food intake in rats and mice, and chronically reduced food intake and body weight in diet-induced obese mice. Ileal l-Phe also reduced food intake in rats. l-Phe stimulated GLP-1 and PYY release, and reduced plasma ghrelin, and also stimulated insulin release and improved glucose tolerance in rats. Pharmacological blockade of the CaSR attenuated the anorectic effect of intra-ileal l-Phe in rats, and l-Phe-induced GLP-1 release from STC-1 and primary L cells was attenuated by CaSR blockade. CONCLUSIONS: l-Phe reduced food intake, stimulated GLP-1 and PYY release, and reduced plasma ghrelin in rodents. Our data provide evidence that the anorectic effects of l-Phe are mediated via the CaSR, and suggest that l-Phe and the CaSR system in the GI tract may have therapeutic utility in the treatment of obesity and diabetes. Further work is required to determine the physiological role of the CaSR in protein sensing in the gut, and the role of this system in humans.

Karydakis Flap With Compressing Tie-over Interrupted Sutures Without Drain versus Standard Karydakis for Treatment of Sacrococcygeal Pilonidal Sinus Disease.

BACKGROUND: Sacroccygeal pilonidal sinus disease is a worldwide health problem, affecting young adults, mainly males, with a tendency for recurrence. Various modalities have been used for treating this condition. The Karydakis procedure is one of most commonly used asymmetric flaps for treating this condition. OBJECTIVE: The study aimed to evaluate the Karydakis procedure with tie-over compressing sutures instead of the routine use of a drain in the treatment pilonidal sinus. DESIGN: This prospective randomized controlled clinical study was conducted between January 2010 and January 2015. SETTINGS: The study was conducted at Minia University Hospital. PATIENTS: The study included 154 patients. Patients were randomly assigned into 2 equal groups. INTERVENTIONS: The patients in group 1 were operated on by the standard Karydakis procedure, and the patients in group 2 were operated on by the Karydakis procedure with tie-over compressing sutures without a drain. MAIN OUTCOMES AND MEASURES: The primary outcomes measured were the incidence of seroma formation, wound complications, length of hospital stay, off-work time, and recurrence rate. RESULTS: All patients were discharged on the same day of surgery in group 2 compared with a mean hospital stay of 4.9 ± 2.4 days in group 1. No patients developed seroma in group 2 compared with 7.8% in group 1. In group 2, 1.3% of patients developed wound infection compared with 9.1% in group 1. The average time for return to work in group 2 was 10.2 ± 1.4 days compared with 12.6 ± 4 days in group 1. No recurrences were noted in group 2 compared with 2.6% in group 1. LIMITATIONS: The feedback about postoperative pain and patient satisfaction about the scar were not investigated. The extent of the disease in both groups was not investigated. The duration of follow-up too short to accurately weight recurrence rate. CONCLUSION: Karydakis flap with tie-over compressing interrupted sutures without a drain is safe, 1-day surgery with the lowest complications rate.

Synthesis, Modelling, and Anticonvulsant Studies of New Quinazolines Showing Three Highly Active Compounds with Low Toxicity and High Affinity to the GABA-A Receptor.

Some novel fluorinated quinazolines (5a-j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, ¹H nuclear magnetic resonance (NMR), 13C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test. The molecular docking was performed for all newly-synthesized compounds to assess their binding affinities to the GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticonvulsant activity for all newly-synthesized compounds. Compounds 5b, 5c, and 5d showed the highest binding affinities toward the GABA-A receptor, along with the highest anticonvulsant activities in experimental mice. These compounds also showed low neurotoxicity and low toxicity in the median lethal dose test compared to the reference drugs. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and explain the possible mechanism for anticonvulsant action. The most active compounds might be used as leads for future modification and optimization.

Self Organizing Map-Based Classification of Cathepsin k and S Inhibitors with Different Selectivity Profiles Using Different Structural Molecular Fingerprints: Design and Application for Discovery of Novel Hits.

The main step in a successful drug discovery pipeline is the identification of small potent compounds that selectively bind to the target of interest with high affinity. However, there is still a shortage of efficient and accurate computational methods with powerful capability to study and hence predict compound selectivity properties. In this work, we propose an affordable machine learning method to perform compound selectivity classification and prediction. For this purpose, we have collected compounds with reported activity and built a selectivity database formed of 153 cathepsin K and S inhibitors that are considered of medicinal interest. This database has three compound sets, two K/S and S/K selective ones and one non-selective KS one. We have subjected this database to the selectivity classification tool 'Emergent Self-Organizing Maps' for exploring its capability to differentiate selective cathepsin inhibitors for one target over the other. The method exhibited good clustering performance for selective ligands with high accuracy (up to 100 %). Among the possibilites, BAPs and MACCS molecular structural fingerprints were used for such a classification. The results exhibited the ability of the method for structure-selectivity relationship interpretation and selectivity markers were identified for the design of further novel inhibitors with high activity and target selectivity.

Radiosensitizing activity of a novel Benzoxazine through the promotion of apoptosis and inhibition of DNA repair.

The DNA dependant protein kinase (DNA-PK) enzyme plays a major part in the repair of double stranded breaks induced by radiation and hence in the radio-resistance of tumour cells. Inhibitors of DNA-PK have been tested successfully in the past for their ability to sensitize cancer cells to the effects of radiation. Here we present a novel benzoxazine, 8-methyl-2-(morpholine-4yl)-7-(pyridine-3-methoxy)-4H-1,3-benzoxacine-4-one (LTU27) and analyse its ability to cause sensitization of lung cancer and colon cancer cells to radiation. There was a significant reduction in survival rate, increase in apoptosis and inhibition in autophosphorylation of DNA-PK and AKT1 after treating them concomitantly with both radiation and LTU27. The mechanism of action appears to be through inhibition of DNA-PK leading to delayed DNA repair and promotion of apoptosis.

Sensitivity, specificity, and accuracy of molecular profiling on circulating cell-free DNA in refractory or relapsed multiple myeloma patients, results of MM-EP1 study.

As a promising alternative to bone marrow aspiration (BMA), mutational profiling on blood-derived circulating cell-free tumor DNA (cfDNA) is a harmless and simple technique to monitor molecular response and treatment resistance of patients with refractory/relapsed multiple myeloma (R/R MM). We evaluated the sensitivity and specificity of cfDNA compared to BMA CD138 positive myeloma plasma cells (PCs) in a series of 45 R/R MM patients using the 29-gene targeted panel (AmpliSeq) NGS. KRAS, NRAS, FAM46C, DIS3, and TP53 were the most frequently mutated genes. The average sensitivity and specificity of cfDNA detection were 65% and 97%, respectively. The concordance per gene between the two samples was good to excellent according to Cohen's κ coefficients interpretation. An increased number of mutations detected in cfDNA were associated with a decreased overall survival. In conclusion, we demonstrated cfDNA NGS analysis feasibility and accuracy in R/R MM patients who may benefit from early phase clinical trial.

The Prevalence of Depression in Patients With Epilepsy in the Kingdom of Saudi Arabia.

Objective Among patients with epilepsy (PWE), the prevalence of depression ranges from 30% to 50%, with a 5-25% prevalence of suicide. Depression and epilepsy affect daily tasks such as driving, employment, and physical activity. Depression is the most common comorbidity among patients with epilepsy. Because both conditions involve pathophysiological changes, treating mood disorders helps treat epilepsy and vice versa. Studies about epilepsy and depression in Saudi Arabia are scarce, and no study has been conducted on this topic at King Fahad Medical City (KFMC); hence, we aimed to determine the prevalence of depression among PWE who were followed up at KFMC. Methods This retrospective hospital-based study was conducted at KFMC in Riyadh, Saudi Arabia. This investigation spanned a period of 10 years, from 2008 to 2018. The study included patients with PWE who were diagnosed with depression. Results According to a study of individuals aged 18 to 69, 73.7% of patients had been diagnosed with chronic depression (i.e., for more than a year); most of these patients had completed elementary school. Higher rates of depression were also observed among elementary school pupils, divorced women, and non-Riyadh residents. A correlation was observed between the severity of depression based on the Patient's Health Questionnaire( PHQ-9) score, which was used to screen for depression and diabetes mellitus (DM), the number of antidepressant medications (ADM) used, the duration of antidepressant use, suicidal ideation or attempts, and the duration of depression. Epilepsy was most prevalent in the temporal lobe, accounting for 22.6% of all cases, and it was managed in 78.2% of the patients. The duration of epilepsy was significantly associated with the severity of depression.

Symptomatic arteriovenous malformation of the thyroid/parathyroid gland: A case report.

Arteriovenous malformations (AVMs) are complex vascular lesions most commonly found in the brain and infrequently found in the head and neck. AVMs are characterized by a tangle of blood vessels called a nidus, which shunts blood from an artery directly to a draining vein. Various treatments are available, including surgical resection and endovascular embolization. Here, we report the case of a 32-year-old male patient who complained of painful pulsating left neck swelling with dysphagia for 1 year, which turned out to be an AVM alongside the left thyroid gland. The AVM was treated by embolization using Onyx in 2 sessions. The patient has been free of symptoms since the treatment.

Retraction: Cerebral Venous Infarct After Recovery From COVID-19 Pneumonia.

[This retracts the article DOI: 10.7759/cureus.19763.].

Reactivation of Herpes Zoster in a Young Patient With Multiple Sclerosis Under Dimethyl Fumarate Treatment and Normal Lymphocyte Subsets Count: A Case Report.

Herpes zoster (HZ) infection results from the reactivation of the varicella-zoster virus (VZV), which remains dormant in the dorsal root ganglia after an initial chickenpox infection. Although HZ appears more common in people with multiple sclerosis (MS) than expected in the general population, few studies have investigated this association, particularly with a normal absolute lymphocyte count (ALC). Additionally, no reported cases have discussed the clinical presentation of such patients. This report describes the case of a 26-year-old female with a known history of relapsing-remitting MS on dimethyl fumarate (DMF) treatment. She presented with a history of painful erythematous blisters, diagnosed as acute HZ infection with a normal ALC. This case provides evidence that warrants further research and attention to the management of patients with MS receiving DMF, particularly regarding infectious risks. It highlights the importance of pharmacovigilance and the potential benefits of VZV and HZ immunization in DMF recipients.

Innovative Reconstructive Management of Foot Macrodactyly in a Pediatric Patient: A Case Report.

Macrodactyly is a rare congenital anomaly characterized by disproportionate hypertrophy of one or more digits or the forefoot, involving some or all tissue types. It is nonhereditary and can present alone or alongside other deformities. Usually, macrodactyly is treated with amputation of the affected toe or finger to reduce the chance of recurrence. In this paper, we present the case of a child with macrodactyly who was treated successfully without amputation and instead with a reconstruction of the toe shape to resemble a near-natural-looking toe with intact functions. The patient was a one-year-old female who presented with macrodactyly of her right great toe, right second toe, and forefoot. She had no history of other congenital deformities or systemic diseases. A reconstruction surgery was performed, which involved debulking the right great toe, right second toe, and forefoot. Also, it included the creation of the first web space and the restoration of the nailbed of the second toe. Postoperative follow-up revealed minimal complications. Thus, a second reconstructive surgery was performed, which included debulking and further reconstruction of the foot to improve the result. Several techniques exist for the reduction of macrodactyly that can achieve optimal results. The choice of technique depends on the specifics of the case and the experience of the surgeon. We therefore hope our technique will be beneficial for the management of future cases of macrodactyly. One year of follow-up after the second operation revealed maintained function and no regrowth recurrence.

Infections occurring following IL6 blockade for the management of cytokine release syndrome in onco-hematology patients.

BACKGROUND: Cytokine release syndrome (CRS) is a common adverse event of CAR T cell or bispecific antibody (bsAb) therapy. Anti-IL6/IL6R drugs are used in the management of auto-immune diseases. Some reports showed increased risk of bacterial infection in this context. In onco-hematology, there are few data about the occurrence of infection after administration of an anti-IL6/IL6R for CRS. METHODS: We retrospectively reviewed all consecutive patients treated in Gustave Roussy Cancer Campus between 2018 and 2021, who received anti-IL6/IL6R for CRS due to bsAb in phase I clinical trials or adoptive cellular therapy (ACT). We constituted a control group including all the patients treated in the same clinical trials or standard of care ACT, naïve of anti-IL6/IL6R. RESULTS: Fifty-two patients have been included. In the anti-IL6/IL6R group (n = 26), five patients developed a grade 2 to 5 infection within a month after anti-IL6/IL6R treatment, including two grade 5 infections. In the control group (n = 26), only one patient had a grade 3 infection. The two patients who had grade 5 infections were treated for diffuse large B cell lymphoma (DLBCL), one with bsAb and the other with CAR T cell. Fifty percent (3/6) of DLBCL patients who received an anti-IL6/IL6R presented an infection, one of which was a grade 5. In solid tumor patients treated with bsAb and anti-IL6/IL6R, only one patient (/9, 11%) developed a grade 2 viral infection. CONCLUSION: It seems that the use of anti-IL6/IL6R in CRS secondary to bsAb administration in solid tumors patients does not significantly increase the risk of infection, as opposed to DLBCL patients where secondary infection might be a concern.