Context:Head and neck space infections source, age, gender, tooth involved, fascial spaces involved, microbiological study of aerobic flora, and antibiotic susceptibilities.Aims:The aim of the present study is to identify causative aerobic microorganisms responsible for deep fascial spaces of head and neck infections and evaluate the resistance of antibiotics used in the treatment of such.Settings and Design:Prospective study in 100 patients.Materials and Methods:This prospective study was conducted on 100 patients who reported in the outpatient department and fulfilled the inclusion criteria to study aerobic microbiology and antibiotic sensitivity in head and neck space infection of odontogenic origin. Pus sample was obtained either by aspiration or by swab stick from the involved spaces, and culture and sensitivity tests were performed.Statistical Analysis Used:Chi-square test and level of significance.Results:Result showed aerobic Gram-positive isolates were 73% and aerobic Gram-negative isolates were 18%. Nine percent cases showed no growth. Streptococcus viridans was the highest isolate in 47% cases among Gram-positive bacteria, and in Gram-negative, Klebsiella pneumoniae was the highest isolate of total cases 11%. Amoxicillin showed resistance (48.4%) as compared to other antibiotics such as ceftriaxone, carbenicillin, amikacin, and imipenem had significantly higher sensitivity.Conclusions:Amoxicillin with clavulanic acid showed (64.8%) efficacy for all organisms isolated, whereas ceftriaxone showed (82.4%) efficacy and could be used in odontogenic infections for both Gram-positive and Gram-negative microorganisms. Substitution of third generation cephalosporin for amoxicillin in the empirical management of deep fascial space infections can also be used. Carbenicillin, amikacin, and imipenem showed (93.4%) sensitivity against all microorganisms and should be reserved for more severe infection. Newer and broad-spectrum antibiotics are more effective in vitro than older narrow spectrum antibiotics.

Context:Evaluation of Maxillofacial fractures in hilly region of Garhwal Himalyas and its relation with age, gender, anatomical location, seasonal variation and treatment provided.Aims:The aim of the present study is to analyze the pattern of maxillofacial fractures in the Garhwal Himalayan region of India and to compare the results with similar studies in India and the rest of the world.Settings and Design:This was a prospective study conducted on 102 patients with 128 facial fractures.Materials and Methods:This study was conducted on 102 patients who were admitted for the treatment of maxillofacial fractures in the Department of Dentistry at Government Medical College, Srinagar, Uttarakhand, India.Statistical Analysis Used:All analyses were performed using Chi-square test and level of significance.Results:Peak incidence was noted in the second to fourth decades of life. Male: female ratio was 4:1. Road traffic accident was the main etiology (42.2%), followed by fall (37.2%) and assault (11.8%). Among other etiology of injury, distinguishing feature was bear bite, which was only seen in winters causing 5.9% of total injury. Fall was reported high in females whereas road traffic accident in males. Mandible was fractured in 73.5% of patients while mid-face in 26.5% of patients. Open reduction with internal fixation was the choice of treatment in 60.8% of cases. Nearly 79.4% of patients were treated under local anesthesia. The mean duration of hospitalization was (standard deviation 5.2 days) 5.3 days.Conclusions:Road traffic accidents still remain the main cause of maxillofacial fractures in developing countries such as India. In hilly area, road traffic accident can be minimized by better wide roads with guide walls/parapet, strict law enforcement for overspeed, overload, and to use seat belts while driving, and use of helmet while riding two-wheeler. Open reduction internal fixation remains the first choice of treatment in facial fractures due to early return of function with minimal morbidity and better nutritional status in patients compared to closed reduction.

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Background: Vaso-occlusive crises (VOCs) are the hallmark of SCD. VOCs and silent vaso-occlusion can lead to complications (eg acute chest syndrome, hepatic/renal dysfunction, chronic pain, multi-organ failure) and premature death. Crizanlizumab, an anti-P-selectin monoclonal antibody (mAb), is authorized in >40 countries to prevent/reduce VOCs in SCD pts aged ≥16 yrs. IRRs are defined as any signs/symptoms (S/S) experienced by pts during/within 24 hrs of infusion of a pharmacologic/biologic agent. IRRs are quite common with mAbs (frequency 1.6‒99%; Rombouts et al Anticancer Res 2020). S/S of IRRs vary; pain events, such as headache, back pain, myalgia, chest pain and joint pain, have been described as S/S of IRRs. Although pain events are known adverse drug reactions in the crizanlizumab label (eg arthralgia, myalgia, pain at various locations), due to data limitations and confounding manifestations of SCD, pain events occurring during/within 24 hrs of crizanlizumab infusion in SUSTAIN were not identified as potential IRRs (Ataga et al N Engl J Med 2017). For pts receiving crizanlizumab, IRR-related pain events may differ in location, severity and/or nature from a pt's usual SCD/VOC pain. Aim: To review data on IRRs presenting as pain events in SCD pts treated with crizanlizumab via reports received by Novartis since approval in Nov 2019. Methods: Data sources included PM reports from providers (spontaneous) and reports from the managed access/pt orientation program. To obtain the reports (which could include ≥1 event), a cumulative custom search of the Novartis safety database was performed up to Jun 2021, using ~111 MedDRA terms associated with potential S/S of IRRs presenting as pain events. IRRs must have occurred during/within 24 hrs of the most recent crizanlizumab infusion, and pain could differ from a pt's usual SCD/VOC, with/without other S/S. IRR incidence was measured by the reporting rate (RR). Reports were not gathered via a uniform data collection system, so there are limitations, including potential underreporting, incompletely documented cases, or bias towards reporting severe events. Results: IRRs presenting as pain events were experienced by 28 pts (Table 1); the most common S/S were back pain, pain in extremity, arthralgia, musculoskeletal chest pain and headache. RR was 1.67 cases per 100 pt-yrs (95% CI 1.11‒2.42). Most pts (n=24) initially experienced IRR at the 1st or 2nd infusion, and the majority recovered within 3 days. IRR recurred on subsequent infusion(s) in 6 pts. Of the 28 pts, 20 (71%) were hospitalized for further treatment, including analgesics, antihistamines, IV fluids and/or steroids. Nine pts (32%) reported SCD complications after IRR (Table 2). Crizanlizumab was discontinued in 23 pts (82%) after their most recent IRR occurrence, including all pts who experienced secondary SCD complications. Discussion: Comprehensive investigation identified 28 pts with reported IRRs presenting as pain events that had a potential causal relationship with crizanlizumab infusion based on temporality. All pts recovered or are recovering, except 1 who had SCD complications and refused blood transfusions for personal reasons. Most pts had initial IRR at the 1st or 2nd infusion and discontinued crizanlizumab after initial IRR; 6 experienced recurrent IRRs on subsequent infusion(s). Resolution time was prolonged for pts who reported known SCD complications following IRR. Causal association of complications following IRR was confounded by the underlying disease and use of steroids to treat IRRs. Systemic corticosteroid exposure in SCD pts has been associated with pain and other complications, from severe VOCs to hemorrhagic stroke and death. No data are available regarding whether the 28 pts had an active VOC or other SCD complications prior to receiving crizanlizumab. Conclusions: Although rare, based on review of PM data, healthcare professionals should be aware of the possibility of IRRs presenting as pain events during or after any crizanlizumab infusion. Crizanlizumab labels have been/are being updated by Novartis to provide information on monitoring for S/S of IRRs presenting as pain events, and guidance on management/prevention of subsequent IRRs, including a statement recommending caution when using corticosteroids in SCD pts. Given the limited data regarding IRRs and predictability of complications, Novartis is committed to further understanding these events. Figure 1 Figure 1. Disclosures Kanter: Fulcrum Therapeutics, Inc.: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Forma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beam: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Graphite Bio: Consultancy; GuidePoint Global: Honoraria; Fulcrum Tx: Consultancy. Shah: Johnson & Johnson: Current equity holder in publicly-traded company; Novartis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Joshi: Novartis Healthcare Private Limited: Current Employment. Mehta: Novartis Healthcare Pvt. Ltd.: Current Employment. Levine: Biontech: Current equity holder in publicly-traded company; Novartis: Current Employment, Current equity holder in publicly-traded company. Arunagiri: Novartis Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Paulose: Novartis Pharmaceuticals Corporation: Current Employment. Donohue: Novartis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Scalera: Novartis Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Manwani: Novartis: Consultancy.

Background: Crizanlizumab, a humanized monoclonal antibody that binds P-selectin and blocks interaction with its ligands (including leukocyte PSGL-1), is under investigation for preventing vaso-occlusive crises (VOCs) in individuals with sickle cell disease (SCD). Crizanlizumab 5.0 mg/kg was shown to significantly reduce the median annual rate of VOCs by 45.3% versus placebo (Hodges-Lehmann median absolute difference of -1.01 vs placebo, 95% CI [-2.00, 0.00]; P=0.01) (Ataga et al. N Engl J Med 2017). Aims: This pooled analysis evaluated key safety endpoints in patients treated with the recommended dose of crizanlizumab (5.0 mg/kg monthly, following 2 loading doses in the first month). Methods: Data were pooled from 2 Phase II studies of SCD patients (any genotype) with a history of VOCs leading to a healthcare visit. SUSTAIN (NCT01895361) was a randomized, placebo-controlled study in patients aged 16-65 years who had experienced 2-10 VOCs in the previous 12 months. SOLACE-adults (A2202) is an ongoing, open-label PK/PD study (NCT03264989) in patients aged 16-70 years who had experienced at least 1 VOC in the previous 12 months; data cut-off for this analysis was 1 March 2019. Adverse events (AEs) were evaluated based on MedDRA v21.1. AE severity in SOLACE was assessed based on CTCAE v5; in SUSTAIN, severity was collected as mild/moderate/severe but then recategorized for this analysis to a 5-point scale similar to CTCAE grading. AEs of special interest (ie known class effects; AEs identified preclinically or in previous studies; or potentially relevant based on the mechanism of action of crizanlizumab) were also evaluated and included infections, infusion-related reactions (IRRs) and hemostatic effects. As monoclonal antibodies can induce an immune response, anti-drug antibodies (ADAs) were also measured. Results: In total, 111 patients (SUSTAIN, n=66; SOLACE, n=45) received crizanlizumab 5.0 mg/kg: 59 females (53.2%) and 52 males (46.8%). Median age was 29 years (range 16-65). The most common SCD genotypes were HbSS (n=73; 65.8%) and HbSC (n=19; 17.1%), and 75 patients (67.6%) were receiving hydroxyurea (HU). Most patients (n=67; 60.4%) had 1-4 VOCs in the previous 12 months. Median duration of exposure to crizanlizumab was 46 weeks (range 4-58). At least 1 AE was reported in 94 patients (84.7%), the most common (≥15%) being headache (n=22; 19.8%), nausea (n=18; 16.2%) and back pain (n=17; 15.3%). AEs were mild/moderate (grade 1 or 2) and resolved spontaneously in most patients; 23 patients (20.7%) had a grade 3 AE and 1 (0.9%) had a grade 4 AE (neoplasm). At least 1 serious AE was reported in 24 patients (21.6%); serious AEs with a suspected relationship to crizanlizumab were reported in 6 patients (5.4%). Twenty-eight patients (25.2%) discontinued treatment prematurely (n=23 in SUSTAIN, n=5 to date in SOLACE): discontinuations due to AEs (bradycardia and breast cancer) occurred in 2 patients (1.8%); neither was considered related to crizanlizumab. There were 2 on-treatment deaths in SUSTAIN, but neither were considered related to crizanlizumab. Infection events were reported in 51 patients (45.9%), the most common (≥5%) being upper respiratory tract infection (n=13, 11.7%) and urinary tract infection (n=11, 9.9%). There were no grade 4 infections and none led to discontinuation. Data suggest no increased risk or severity of infection in studies with crizanlizumab. Two patients (1.8%) experienced IRRs; the events were not serious and did not lead to discontinuation. Bleeding events were rare, with most observed hemostatic AEs being abnormal laboratory parameters occurring only once. Treatment-induced ADAs were transiently detected in 1 patient (0.9%) and spontaneously resolved. There were no clinically relevant laboratory (hematology, biochemistry, liver) or ECG abnormalities, or vital sign changes, and no notable differences in the AE incidence rates by gender, ethnicity or HU use. Conclusions: This pooled analysis shows that crizanlizumab 5.0 mg/kg was well tolerated, with a favorable safety profile, in patients with SCD and a history of VOCs. Most AEs were mild/moderate, and discontinuations due to AEs were infrequent. The immunogenic potential of crizanlizumab appears low and there is currently no evidence for an increased risk of infection or bleeding. SOLACE-adults and SOLACE-kids (6 months to <18 years) are ongoing, and the randomized Phase III STAND trial is recruiting. Disclosures Kanter: bluebird bio, Inc.: Consultancy; SCDAA: Membership on an entity's Board of Directors or advisory committees; NHLBI: Membership on an entity's Board of Directors or advisory committees; Rockpointe: Honoraria; Peerview: Honoraria; Jeffries: Consultancy; Medscape: Honoraria; GLG: Consultancy; Cowen: Consultancy; Guidepoint Global: Consultancy; Sangamo: Consultancy, Honoraria; Modus: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Imara: Consultancy. Liles:Novartis: Other: PI on clinical trial Sickle cell ; Shire: Other: PI on clinical trial Sickle cell ; Imara: Other: PI on Clinical trial- Sickle cell . Brown:Novartis, Inc: Research Funding. Kutlar:Bluebird Bio: Other: DSMB Member; Micelle Biopharma: Other: DSMB Chair; Novartis: Consultancy; Global Blood Therapeutics, Inc. (GBT): Research Funding; Novo Nordisk: Research Funding. Elliott:Novartis: Employment, Equity Ownership. Shah:Novartis Pharmaceuticals: Employment, Other: Shareholder. Lincy:NOVARTIS PHARMA AG: Employment. Poggio:Novartis: Employment. Ataga:Advisory Board: Global Blood Therapeutics, Novartis: Membership on an entity's Board of Directors or advisory committees, Other: VINDICO WILL FORWARD DISCLOSURES ONCE RECEIVED AND SIGNED NOT RECEIVED TO DATE; VINDICO WILL FORWARD DISCLOSURES ONCE RECEIVED AND SIGNED NOT RECEIVED TO DATE: Other: VINDICO WILL FORWARD DISCLOSURES ONCE RECEIVED AND SIGNED NOT RECEIVED TO DATE; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Emmaus Life Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees.