Prolonged Treatment Duration Research Articles

Brucellosis of the Spine in Children-An Analysis of 5 Children From an Endemic Setting.

Brucellosis of the spine is quite common among adults in endemic regions. The incidence of brucellosis of the spine affecting children is very rare. This article describes the clinical characteristics, diagnosis, management and outcome of children with brucellosis of the spine. It also aims to create awareness among all health care professionals, especially spine surgeons, regarding this rare entity. This was a retrospective study of children aged less than 15 years who were diagnosed and treated for brucellosis of the spine. Confirmed cases of brucellosis in children who had completed a full course of a triple-drug regimen as per Centers for Disease Control and Prevention (CDC) guidelines were included. Outcome analysis included both clinical and radiological measures. Clinical measures included pain, neurological status, and return to school. Resolution of the abscess and sclerosis of the involved vertebra were taken as the radiological measure. A total of 5 children (4 boys and 1 girl) with an average age of 10 years, ranging from 6 to 14 years, fulfilled the inclusion criteria. The mean follow-up period was 32 months. All children presented with fever, back pain, and constitutional symptoms. Two of them had neurological deficits, and posttreatment, they improved to near normal neurological status. Only 1 child with an epidural abscess compressing the lumbar canal required surgical intervention. All the children were treated with a triple-drug regimen. Longer duration of treatment (14 months) was given for 2 children with history of relapse. All children were healed of the disease without any sequalae or relapse. Blood culture and standard agglutination tests are mandatory for the diagnosis of brucellosis. Children tolerated the triple-drug regimen well. Prolonged duration of treatment was required for children with relapse. Health education to all treating health care professionals and parents is of paramount importance for treatment and control of this endemic disease.

RNA Polymerase 1 Transcription Inhibitor CX-5461 in Patients with Advanced Hematologic Malignancies: Results of a Phase I First in Human Study

▪RNA polymerase I (Pol I) transcription of the ribosomal RNA (rRNA) genes, a rate-limiting step for growth and proliferation, is a highly regulated process downstream of many oncogenic pathways. Dysregulation of ribosome biogenesis is a feature of numerous cancers (Bywater Nat Rev 2013 ).CX-5461, a selective inhibitor of Pol I transcription (Senhwa Biosciences, San Diego, USA), has ~200-fold selectivity for inhibition of Pol I over Pol II (Drygin Can Res 2011 ). Inhibition of Pol I transcription by CX-5461 induces a p53 independent nucleolar stress response and a nucleolar specific DNA damage response (Quin Oncotarget 2016 ). CX-5461 provides survival benefit in mouse models of lymphoma, myeloid leukemia and myeloma (Hein Blood 2017) .Methods: We initiated a first in class, first in human, phase I dose escalation study of CX-5461 in adult patients with advanced hematologic cancers, with no standard therapeutic options, adequate organ function and performance status to determine maximum tolerated dose (MTD), safety, pharmacokinetic (PK) profile and antitumor activity.CX-5461 was administered by 1 hour IV infusion 3 weekly. Dose escalations were planned in 7 cohorts (25 - 450 mg/m2), in an accelerated design, with change to a 3+3 design based on predefined toxicity criteria.Inhibition of Pol I transcription rate was measured via RNA-FISH, quantitating the abundance of 47S pre-rRNA levels in peripheral blood mononuclear cells (PBMC) and tumor tissue, at various time points following cycle 1. Skin biopsies from normal skin and rash areas were studied after the observation of photosensitivity in patients in cohort 1.Results: 16 patients (6 myeloma, 2 Hodgkin lymphoma, 6 Non Hodgkin lymphoma (NHL), 1 TPLL, 1 CLL) were treated in 5 cohorts (25 - 250 mg/ m2), for a median of 2 (1 - 18) cycles. The MTD was 170 mg/ m2. The dose limiting toxicity was palmar plantar erythrodysaesthesia in 2 patients at 250 mg/ m2. One of these patients continued treatment for 17 further cycles at 170 mg/ m2. Eight patients (50%) had grade </=3 treatment related photosensitivity across all dose cohorts, this did not recur on re-exposure with appropriate protection. No other grade 3+ treatment related adverse events were observed.The average terminal half-life (T1/2) showed an increasing trend with dose escalation, in a profile consistent with enterohepatic recycling. The maximum T1/2 noted was 92 hours in cohort 5. Linear behaviors were generally observed in Cmax and AUC exposure parameters.The best response seen was an excellent prolonged partial response in 1 patient with anaplastic large cell lymphoma (18 cycles) and stable disease in 3 patients with myeloma (4 - 6 cycles) and 2 with diffuse large B-cell lymphoma (4 - 16 cycles). Clinical and radiologic response was noted in an area of high grade transformation in a patient with cutaneous T-Cell lymphoma (CTCL).Consistent, significant decreases in Pol I transcription were observed at 1hr post-infusion in PBMC. The average level of inhibition was 49.0% (22.9 - 69.9%), 51.1% (34.4 - 64.4%), 19.6% (-72.0 - 69.7%), 47.3% (46.5 - 48.0%) and 38.6% (6.8 - 70.4%) in cohorts 1 - 5 respectively (Fig 1). On target activity at 24hrs was observed in most tumor biopsies, where the level of inhibition was variable (10/13; median range: 4.8 - 68.9 %) (Fig 2).Targeted exon sequencing determined TP53 mutational status in selected patients (n=13). 4 patients with mutations experienced early disease progression. In TP53 wildtype patients, 4 achieved periods of stable disease. In a CTCL patient, stabilization of p53 protein levels and increase in the p53 target gene p21 occurred in an area of high grade transformation where response was observed (Fig 3).A spongiotic or parakeratosis reaction pattern was observed in biopsies from the photosensitivity rash, with increase in p53 IHC expression in the epidermis of normal skin following CX-5461 exposure (Fig 4).Conclusion: Our first in human study of the Pol I inhibitor CX-5461, has determined a MTD of 170 mg/ m2 every 3 weeks, with a predictable PK profile. The drug is well tolerated and compatible with a prolonged duration of treatment. Photosensitivity can be a significant adverse event independent of dose, which is manageable by careful attention to preventive measures. Durable periods of response or stability have been noted in heavily pretreated chemorefractory patients with NHL and myeloma. Further studies to explore weekly dosing regimens are planned. [Display omitted] DisclosuresKhot:Celgene: Consultancy; Janssen: Consultancy; Amgen: Other: Travel Grant. Lim:Senhwa Biosciences: Consultancy, Equity Ownership. Soong:Senwa Biosciences: Employment, Equity Ownership. Harrison:Celgene: Consultancy, Research Funding, Speakers Bureau.

Patient Characteristics and Preferences Regarding Anticoagulant Treatment in Venous Thromboembolic Disease.

Background: Anticoagulants are the recommended treatment for venous thromboembolic disease (VTE). The mode of anticoagulant administration may influence compliance, and therefore the effectiveness of the treatment. Unlike in atrial fibrillation or cancer-associated thrombosis, there is only limited data on patient preferences regarding the choice of anticoagulation in VTE. This study aims to evaluate patient preferences regarding anticoagulants in terms of administration: types (oral or injectable treatment) and number of doses or injections per day.Patients and Methods: This is a national survey through a questionnaire sent by e-mail to 1936 French vascular physicians between February and April 2019. They recorded the responses for each patient admitted for VTE.Results: Three hundred and eleven (response rate of 16%) of the 1936 contacted physicians responded for 364 patients. Among these, there were 167 fully completed questionnaires. Most patients (63%) express concerns about VTE and prefer oral treatment (81.5%), justified by the ease of administration (74%) and a fear of the injections (22%). When patients were taking more than three oral treatments they statistically chose injectable treatment more often (54%) than oral treatment (25%, p = 0.002). Patients who chose injectable treatment were also older (70 ± 16 vs. 58 ± 17 years old, p = 0.001). There was no statistically difference in anticoagulation preference according to gender or to the expected duration of treatment (6 weeks, 3 months, 6 months or unlimited). When oral treatment was preferred (81%), most chose oral treatment without dose adjustment and biomonitoring (74.3%). Among them, very few (5.8%) preferred a twice-daily intake.Conclusion: Patient preference in terms of anticoagulant treatment in VTE disease is in favor of oral treatment without adjustment or biomonitoring and with once-daily intake. When an injectable treatment is chosen, a prolonged duration of treatment does not seem to be a constraint for the patient.Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT03889457].

ENDOSCOPIC VS COMBINED MEDICAL AND SURGICAL MODALITIES OF TREATMENT OF RADIATION INDUCED PROCTOCOLITIS – OUR INSTITUTE EXPERIENCE

Background: GIGastrointestinal injury may occur following irradiation of thoracic,abdominal,and pelvic malignancies limiting radiation doses that can be delivered as well as causing significant morbidity requiring intervention. Radiation proctocolitis, both acute and chronic, is one such complication requiring multidisciplinary management for good outcomes.We analyzed the injury with respect to spectrum of injury, severity, morbidity and compared endoscopic vs combined medical and surgical modalities of treatment. Methods: Patients with acute and chronic radiation proctocolitis defined as illness presenting before and after 3 months respectively,of radiation treatment were included in the study.The study period was five years. Results: Total number of patients studied were 75.Acute disease was seen in 5 patients,presenting predominantly with diarrhea, abdominal pain and acute intestinal pseudo-obstruction. Chronic radiation proctocolitis was seen in 70 patients. Bleeding per rectum was the most common symptom. Anemia was the commonest sign. Grade 2 injury was most commonly seen. Pharmacotherapy was equally effective in grade 1 injury whereas Endoscopic treatment was superior to pharmacotherapy in Grade 2,3. Surgery offered lesser rates of rehospitalization in grade 3 but was associated with higher complications. There were no deaths in endoscopic arm while there were 2 deaths in pts who required surgery. Surgical combined with medical was superior to endoscopic treatment in grade 4 while local agents were ineffective.Preventive strategies prior to radiation were associated with lower grade of injury. Conclusion: Radiation proctocolitis causes significant morbidity requiring prolonged treatment and hospitalization. Dose and duration of radiation had direct relation to the severity of injury. Concurrent chemotherapy had no effect on severity of injury.Our study showed acute proctocolitis required predominantly supportive medical treatment.Chronic form from grade 1 to 3 required predominantly endoscopic treatment with prolonged duration of treatment but less morbidity.Grade 4 required surgical and intensive care and local therapy was ineffective.

FC 0104-WEEK ANTIBIOTIC THERAPY PREVENTS RECURRENT RENAL CYST INFECTIONS IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Renal cyst infection (CI) is a major complication of autosomal dominant polycystic kidney disease (ADPKD), associated with frequent hospitalization, worsening of kidney function and significant mortality. Data regarding treatment are scarce and recommendations only expert-based, with low level of evidence. Prolonged treatment duration and use of lipid-soluble antibiotics may increase antibiotic concentration in infected kidney cysts. However, benefits of this strategy have never been investigated in clinical practice. Method We undertook a monocentric retrospective study of CI in ADPKD patients from 2000 to 2018. CI were classified as “definite” (microbiologically proven), “probable” (clinical/biological and radiological signs) or possible (clinical/biological signs). Determinants of treatment failure and recurrences were studied. Results 139 CI (11 “definite”, 74 “probable”, 54 “possible”) were compiled among 90 patients. Median age was 53 years. 28/90 (31%) were kidney transplant recipients. Escherichia coli was identified in 89/106 (84%) episodes. Treatment failure was reported in 22/139 (16%), and found associated with cyst diameter &amp;gt;5cm (80% vs 36%, P&amp;lt;0.01), cyst wall thickening (53% vs 12%, P&amp;lt;0.001), cyst septations (18% vs 1%, P&amp;lt;0.01), intracystic gas (18% vs 1%, P&amp;lt;0.01), kidney abscess (35% vs 1%, P&amp;lt;0.001), higher C-reactive protein level (210 [140-358] vs 145 [99-213] mg/L, P&amp;lt;0.01) or documentation of Staphylococcus aureus and lugdunensis (P&amp;lt;0.001). Recurrence was reported in 20/139 (14%) cases within 1-year follow-up. Recurrence rate was lower in patients treated with lipid soluble antibiotics than with non-lipid soluble antibiotics (HR=0.34 [0.12-0.97], p=0.045). Most importantly, cases with definite and probable CI experienced significantly fewer recurrences when treated with longer treatment duration: 81% for treatment &amp;lt;21 days, 47% for 21-27 days, but only 2% for ≥28 days (p&amp;lt;0.0001). Conclusion Treatment of kidney CI should last ≥28 days and include when possible lipid soluble antibiotics.

Linezolid Induced Thrombocytopenia: A Case Report

Linezolid (LZD) is an antimicrobial agent with a broad spectrum of activity against virtually all clinically important Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphylococci (MRCoNS) and vancomycin-resistant enterococci (VRE). Thrombocytopenia (TP) is a common adverse effect of Linezolid (LZD). Prolonged treatment duration, renal insufficiency, chronic liver disease, malignancy, previous vancomycin use, baseline platelet count, and lower body weight have been reported as possible risk factors for LZD-associated TP. Here, we illustrate a case of a 51-year-old male patient diagnosed with pancreatitis and urinary tract infection and was prescribed several antibiotics including Linezolid. In this case, platelets count which were initially normal started declining from day 7 of initiating Linezolid. Linezolid was withdrawn from treatment from day 9. Platelet count gradually came back to normal on day 16. This suggests reversible type of thrombocytopenia by Linezolid. This case illustrates need for careful observation of platelet count during the treatment with Linezolid.&#x0D; Keywords:&#x0D; Linezolid, Thrombocytopenia, Dechallenge

External apical root resorption after orthodontic treatment: Incidence, severity and risk factors.

Background. This study aimed to evaluate the incidence and severity of orthodontically induced inflammatory external apical root resorption (OIIEARR) and the relationship between OIIEARR and possible risk factors such as orthodontic treatment type, treatment duration, gender, and age of the patients. A further aim was to determine the prevalence of OIIEARR in different tooth groups. Methods. The study sample consisted of 1356 orthodontically treated patients (857 females and 498 males; mean age: 14.4±2.8 years). OIIEARR was evaluated using pre- and post-treatment panoramic radiographs for all the tooth groups. Teeth with severe resorption were also assessed. Patient- and treatment-related risk factors for OIIEARR were assessed statistically using Pearson’s chi-squared test, independent-samples t test, and one-way ANOVA. Results. The incidence of severe root resorption following orthodontic treatment was 14.8%. Males exhibited a higher incidence of root resorption compared to females. Orthodontic treatment duration and treatment with extractions were positively correlated with OIIEARR (P < 0.05). OIIEARR was observed most frequently in maxillary incisors, followed by mandibular incisors. Conclusion. Orthodontic treatment with extraction, prolonged treatment duration, and large movements of the incisors should especially be taken into consideration for OIIEARR risk. Routine radiographic follow-up during orthodontic treatment is recommended.

Diabetes Concordant Comorbidities and Associated Factors Among Adult Diabetic Out-Patients at Hiwot Fana Specialized University Hospital, Harar, Eastern Ethiopia: a Cross-Sectional Study.

BackgroundNowadays diabetic comorbidities constitute a major public health problem in Ethiopian context. However, there is a dearth in epidemiology and risk factors of diabetic comorbidity in Ethiopia, particularly in the study setting. Therefore, this study was conducted to determine the prevalence and identify factors associated with concordant diabetic comorbidities among diabetic out-patients at Hiwot Fana Specialized University Hospital (HFSUH), EasternEthiopia.MethodologyA hospital-based cross-sectional study was conducted by reviewing medical record charts of adult diabetic outpatients. Bivariable and multivariable logistic regression analysis was carried out by using STATA version 16.0. To measure the strength of association an Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) was used. Moreover, variables with p-value ≤ 0.05 were considered as statistically significant with the outcome variable.ResultsIn this study, it is found that the overall prevalence of concordant comorbidity among adult diabetic out-patients was 55.8% (95% CI: 50.3–61.3). Moreover, more than two-third of patients, 72.73% were diagnosed for type two diabetic mellitus (T2DM). Among specified comorbidities about 42.3% were hypertension, 21.63% were obesity, and 13% were multi-morbidity. Age ≥ 55 years (AOR: 7.52, 95% CI: 1.24, 45.75), T2DM (AOR: 9.01, 95% CI: 1.50, 54.04), 2–5 years duration of treatments (AOR: 0.23, 95 CI: 0.078, 0.691), and poor glycemic control (AOR: 4.4 1, 95% CI: 2.34, 8.32) were factors significantly associated with concordant diabetic comorbidity.ConclusionFrom the study conducted, the higher prevalence of concordant comorbidity among diabetic patients was investigated. Furthermore, older in age, T2DM, prolonged duration of treatment, and poor glycemic control were factors associated with diabetic comorbidities. Early detection and appropriate treatment of diabetic comorbidities are very important for better patient’s quality of life and functionality.

Is vacuum-assisted closure therapy feasible for children with deep sternal wound infection after cardiac surgery? The pooling results from current literature.

Vacuum-assisted closure (VAC) has been used for children with deep sternal wound infections (DSWI); however, the safety and efficiency have not been determined. A meta-analysis was performed for outcomes of VAC therapy in children with DSWI after cardiac surgery. Electronic databases, including PubMed, Scopus, and Cochrane Library CENTRAL were searched systematically from January 1990 to October 2020 for the literature which reported the outcomes of VAC therapy for children with DSWI after cardiac surgery. Meta-regression and subgroup analyses were performed to find risk factors for prolonged length of VAC therapy and hospital stay. Eleven studies were included in this study, involving 217 subjects. VAC therapy was performed due to mediastinitis after congenital heart diseases (CHD) repair. In children with DSWI after cardiac surgery, length of VAC therapy, and hospital stay were 11.1days (95% CI, 9.6-12.5days) and 29.8days (95% CI, 22.8-36.9days), respectively. Incidence of infectious and wound-related complications was 8.5% (95% CI, 4.1%-13.0%). Overall mortality in this setting was 5.8% (95% CI, 2.5%-9.1%). In conclusion, in children with DSWI after cardiac surgery, length of VAC therapy and hospital stay were 11.1 and 29.8days, respectively. Overall mortality was 5.8%. Although not significant, delayed chest closure, complex CHD, and Gram-negative bacilli/fungal infections may potentially contribute to prolonged duration of VAC treatment.

Evaluating Clostridioides difficile infection (CDI) treatment duration in hematology/oncology patients receiving concurrent non-CDI antibiotics.

To determine the impact of Clostridioides difficile infection (CDI) treatment duration on CDI recurrence in hematology/oncology patients receiving concurrent non-CDI antibiotics. This multi-site, retrospective study examined hematology/oncology patients age ≥18 years hospitalized with active CDI who received ≥1 dose of concurrent non-CDI antibiotics between September 2013 and June 2019. All patients were classified by two definitions for statistical analysis: standard (10-14 days) versus prolonged (>14 days) duration of CDI treatment and non-extended (≤24 hours after stopping non-CDI antibiotics) versus extended (>24 hours after stopping non-CDI antibiotics) CDI treatment. Primary outcome was CDI recurrence within 180 days of completing CDI treatment. Secondary outcomes included hospital length of stay (LOS) as well as mortality and incidence of vancomycin-resistant enterococcus (VRE) infections at 180 days. Of the 198 patients included, 112 were classified as prolonged versus 86 standard duration and 138 were classified as extended versus 60 non-extended duration. After accounting for demographic differences, no difference existed in the primary outcome of CDI recurrence in either prolonged versus standard or extended versus non-extended analysis (all p > 0.05). Patients who received prolonged versus standard CDI treatment had longer LOS (p < 0.0001) while no difference existed in extended versus non-extended (p > 0.05). No difference in mortality existed in prolonged versus standard (p > 0.05) while those who received extended versus non-extended CDI treatment had significantly lower mortality (p = 0.0008). Neither prolonging CDI treatment beyond standard duration nor extending duration beyond end of non-CDI antibiotics was associated with decreased CDI recurrence rate.

Umbilical Cord Separation Time and Influencing Factors in Very-Low-Birth-Weight Preterm Neonates.

The average time for umbilical cord separation in term neonates is 7 to 10 days. Prematurity, phototherapy, prolonged duration of antibiotic treatment, and parenteral nutrition are other factors which were demonstrated to delay cord separation. In the previous studies including greater premature infants, the time of separation of the umbilical cord was shown to vary 2 to 3 weeks. We aimed to determine the cord separation time and associated factors in very-low-birth-weight (VLBW) infants. In this retrospective study, VLBW infants (birth weight [BW] <1,500 g, gestational age [GA] < 32 weeks) without umbilical catheterization were included. Specific cord care was not applied. The cord separation time, gender, mode of delivery, presence of sepsis, duration of antibiotic treatment, serum free thyroxine, free triiodothyronine (FT3), thyroid-stimulating hormone, lowest leukocyte, polymorphonuclear leukocytes (PMNLs), and platelet counts were recorded. The study included 130 infants (GA: 29 ± 2 weeks, BW: 1,196 ± 243 g). Mean cord separation time was 14 ± 5 days, while 95th percentile was 22nd day of life. A positive correlation was demonstrated between duration of antibiotic treatment and cord separation time (p < 0.001, r: 0.505). Cord separation time did not differ regarding gender or mode of delivery. Corrected leukocyte count (p = 0.031, r: -0.190) and PMNL count (p = 0.022, r: -0.201), and serum FT3 level (p = 0.003, r: -0.261) were found to be negatively correlated with cord separation time. The cord separation time was found to be delayed in the presence of sepsis (with sepsis: 18 ± 7 days and without sepsis: 13 ± 3 days; p = 0.008). Sepsis was found to delay the cord separation time beyond second week (odds ratio = 6.30 [95% confidence interval: 2.37-15.62], p < 0.001). The 95th percentile for cord separation time was 22nd day. Sepsis might be either the reason or the consequence of delayed cord detachment. The exact contribution of low serum FT3 levels to the process of cord separation should be investigated in further studies. · Mean cord separation time was 14 ± 5 days, while 95th percentile was 22nd day, in VLBW infants.. · Sepsis was found to delay the cord separation time by sixfold beyond second week.. · Serum free triiodothyronine level was negatively correlated with cord separation time..

Treating Glioblastoma Multiforme (GBM) with super hyperfractionated radiation therapy: Implication of temporal dose fractionation optimization including cancer stem cell dynamics.

PurposeA previously developed ordinary differential equation (ODE) that models the dynamic interaction and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC) was used to explain the definitive treatment failure in Glioblastoma Multiforme (GBM) for conventionally and hypo-fractionated treatments. In this study, optimization of temporal dose modulation based on the ODE equation is performed to explore the feasibility of improving GBM treatment outcome.MethodsA non-convex optimization problem with the objective of minimizing the total cancer cell number while maintaining the normal tissue biological effective dose (BEDnormal) at 100 Gy, equivalent to the conventional 2 Gy × 30 dosing scheme was formulated. With specified total number of dose fractions and treatment duration, the optimization was performed using a paired simulated annealing algorithm with fractional doses delivered to the CSC and DCC compartments and time intervals between fractions as variables. The recurrence time, defined as the time point at which the total tumor cell number regrows to 2.8×109 cells, was used to evaluate optimization outcome. Optimization was performed for conventional treatment time frames equivalent to currently and historically utilized fractionation schemes, in which limited improvement in recurrence time delay was observed. The efficacy of a super hyperfractionated approach with a prolonged treatment duration of one year was therefore tested, with both fixed regular and optimized variable time intervals between dose fractions corresponding to total number of fractions equivalent to weekly, bi-weekly, and monthly deliveries (n = 53, 27, 13). Optimization corresponding to BEDnormal of 150 Gy was also obtained to evaluate the possibility in further recurrence delay with dose escalation.ResultsFor the super hyperfractionated schedules with dose fraction number equivalent to weekly, bi-weekly, and monthly deliveries, the recurrence time points were found to be 430.5, 423.9, and 413.3 days, respectively, significantly delayed compared with the recurrence time of 250.3 days from conventional fractionation. Results show that optimal outcome was achieved by first delivering infrequent fractions followed by dense once per day fractions in the middle and end of the treatment course, with sparse and low dose treatments in the between. The dose to the CSC compartment was held relatively constant throughout while larger dose fractions to the DCC compartment were observed in the beginning and final fractions that preceded large time intervals. Dose escalation to BEDnormal of 150 Gy was shown capable of further delaying recurrence time to 452 days.ConclusionThe development and utilization of a temporal dose fractionation optimization framework in the context of CSC dynamics have demonstrated that substantial delay in GBM local tumor recurrence could be achieved with a super hyperfractionated treatment approach. Preclinical and clinical studies are needed to validate the efficacy of this novel treatment delivery method.

Predictors of recurrent strictures after oesophageal atresia repair

Background: Anastomotic strictures continue to complicate the outcome after oesophageal atresia (OA) repair. Multiple variables contribute to the development of strictures, and oesophageal dilatations are the mainstay of treatment. We aim to analyse the factors that impact the timing for initiation of oesophageal dilatations, the duration, frequency, and success of the dilatation regimen for OA. Methods: It was a retrospective review of data (13-year) of children who underwent repair for Gross type C OA (OA with distal tracheo-oesophageal fistula). The delayed anastomosis was performed for long gap OA. Leaks were clinically obvious or identified on contrast swallow. Strictures that were symptomatic underwent oesophageal dilatations. Results: The data of 72 children were analysed. The stricture rate was 37.5%. Ten had delayed repair, out of which 50% developed strictures compared to 35.5% who had a primary repair (P=0.48). There was no statistical difference in the mean birth weight (BW) and gestational age (GA) of children who developed strictures compared to those with no strictures (2.74kg vs 2.63Kg; P =0.548; 37.4 weeks vs 37.3 weeks; P=0.9). Children that underwent a delayed repair required significantly more dilatation sessions (12 vs 2 median sessions; P =0.001) and had a significantly prolonged duration of treatment (610 vs 63 median days; P = 0.013). There was a significant negative correlation between the GA and BW and the number of dilatation sessions required (P=0.03 and P=0.02, respectively). Linear regression revealed that delayed repair was the most important factor related to the number of dilatation sessions required (p &lt;0.001); this was followed by lower GA or BW (p = 0.0265) and early onset of dilatations (p=0.0471). Conclusions: The early onset of oesophageal dilatation for oesophageal strictures or when they occur in premature babies or those that have had a delayed repair, it should be anticipated that they would be refractory or recurrent.

Occlusal outcome after orthodontic treatment with preadjusted straight-wire and standard edgewise appliances : Aretrospective cohort study.

PurposeOrthodontic fixed appliances have been proven to be effective in treating a wide variety of malocclusions, and different types of appliances have emerged during recent decades. However, the comparative effects of different appliances have not been adequately assessed. Thus, the aim was to assess the occlusal outcome of orthodontic treatment with preadjusted straight-wire (SWIRE) and standard edgewise (SEDGE) appliances.MethodsIn all, 56 patients (mean age: 13.5 years; 45% male) receiving extraction-based treatment with either SWIRE or SEDGE appliances were included. Between-group differences in the occlusal outcome assessed with the American Board of Orthodontists Objective Grading System (ABO-OGS) and treatment duration were analyzed statistically at the 5% level.ResultsThe average ABO-OGS score was 31.3 ± 7.2 points and 34.0 ± 10.4 points in the SWIRE and SEDGE groups with no statistically significant difference between groups (P = 0.26). Treatment duration was significantly shorter in the SWIRE group compared to the SEDGE group, with an average difference of −6.8 months (95% confidence interval [95% CI] = −9.6 to −4.0 months; P < 0.001). Likewise, fewer visits were needed with SWIRE compared to SEDGE appliances with an average difference of −7.2 visits (95% CI = −10.3 to −4.2 visits; P < 0.001). Adjusting for the influence of any potential confounders did not considerably impact the results.ConclusionSimilar treatment outcomes were observed after premolar extraction treatment with SWIRE and SEDGE appliances. On the other hand, SEDGE appliances were associated with prolonged treatment duration and more visits needed to complete treatment compared to SWIRE appliances.Supplementary Information The online version of this article (10.1007/s00056-020-00273-z) contains supplementary material, which is available to authorized users.

Clinical efficacy and safety of omalizumab in conventional treatment-resistant vernal keratoconjunctivitis: Our experience and literature review.

Clinical efficacy and safety of omalizumab in conventional treatment-resistant vernal keratoconjunctivitis: Our experience and literature review.

Treatment of superficial vein thrombosis with intermediate dose of tinzaparin: A real word cohort study - The SeVEN EXTension study.

To assess the treatment of superficial vein thrombosis (SVT) with intermediate dose of tinzaparin in a setting of real world practice. Prospective observational study of consecutive patients treated by vascular physicians in the private sector with tinzaparin (131 IU/Kg) once daily. Treatment duration was at the treating physician's discretion. The outcomes of the study were symptomatic venous thromboembolism, extension of thrombus and bleeding complications. 660 patients were included and followed up for at least 3 months. Median duration of treatment was 30 days (14-120). History of prior deep vein thrombosis (HR 2.77; 95% CI= 1.18-6.49; p = 0.018) and current SVT above the knee (HR1.84; 95% CI = 1.33-3.53; p = 0.0002) were associated with prolonged treatment duration. Primary efficacy outcomes occurred in 20 (3%) patients. The median time to the event was 24 (6-92) days and was not related to treatment duration. Tinzaparin at intermediate dose is an effective and safe treatment for SVT.

Tamoxifen. A treatment for meningioma?

BackgroundNo large-scale study evaluating the usefulness of tamoxifen after meningioma surgery has been undertaken. MethodsWe processed the French Système National des Données de Santé (SNDS) database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve cases of meningiomas operated between 2007 and 2017. Survival analyses were performed using a matched cohort study. Results251 patients treated by tamoxifen were extracted from a nationwide population-based cohort of 28 924 patients operated on for a meningioma over a 10-year period. 94% were female and median age at meningioma first surgery was 57 years IQR[47–67]. Tamoxifen treatment median duration was 1.4 years IQR[0.4–3.2]. Tamoxifen treatment median cumulative given dose was 11.4 gs, IQR[3.6–24.9]. There was a strong positive correlation between treatment duration and cumulative dose (τ=0.81, p<0.001). 6% of the patient had to be reoperated for a meningioma recurrence and 26.3% had radiotherapy. OS rates at 5 and 10 years were: 92.3%, 95%CI[90.3–94.3] and 81.3%, 95%CI[75.2–88] respectively. These 251 patients were matched by gender, age at surgery and grade with the same number of subjects within the nationwide cohort. Nor overall (HR=1.46, 95%CI[0.86- 2.49], p=0.163) or progression-free survival (HR=1.2, 95%CI[0.89- 1.62], p=0.239) were significantly improved by the tamoxifen treatment. ConclusionUsing this unique database, in the setting of breast cancer, we could not conclude on a favourable effect of tamoxifen to prevent recurrence after meningioma surgery or to increase meningioma-related survival even in case of prolonged treatment duration or high cumulative given dose.

299. Paediatric Collaborative Network on Infections in Canada (PICNIC) Study of the Current Landscape of Gram Negative Bacteremias

BackgroundAntimicrobial resistance is a public health threat, invasive infection from multi-drug resistant gram-negative (MDRGN) pathogens is associated with significant morbidity and mortality. The incidence of MDRGN bacteremia in Canada is rising, and pediatric data is limited.MethodsThis retrospective chart review of paediatric patients with gram negative bacteremia in a multicenter PICNIC database (n=7 centers) from 2013 to 2017. MDRGN was defined as enterobacteriaceae that were resistant to third generation cephalosporins (including ESBL, CPE). Ethics approval was obtained at all sites, and data was entered into a secure REDCAP database, descriptive statistics are described herein.ResultsOf the 676 bacteremia patients in the database, 214 (31.7%) were gram negative pathogens. E. coli was the most frequent pathogen (59.8%, of which 22 of 128 were MDR), followed by Klebsiella (31.8%, of which 9 of 68 were MDR). Of the 31 MDRGNs, 19 were ESBL, 1 was a CPE, and 11 were nonspecific mechanisms of resistance. There were no multidrug resistant Pseudomonas, Stenotrophomonas, or Acinetobacter. The majority of patient were less than 3 months of age (59.3%) and were male (58.8%). The majority had an underlying comorbid condition; hematoncologic diagnosis accounting for 14.5%. Length of stay varied from 1 to 742 days (mean 72, standard deviation 88). 11% required admission to ICU, 10% required removal of a intravascular catheter, 7% required a change in ventilation status, 2% requiring procedural source control, and there was an 8% mortality rate. Treatment duration greater than 14 days occurred in 123 patients (61% of patients). ConclusionThis preliminary analysis of a multicenter review of pediatric gram negative bacteremias demonstrates a higher risk in neonates with comorbid conditions. A surprisingly prolonged treatment duration of greater than 14 days occurred in the majority of patients. Further analysis to assess factors associated with prolonged treatment durations, MDR infection, and complications is required. Gram negative bacteremia remains a significant cause of morbidity and mortality in pediatric patients.Disclosures All Authors: No reported disclosures

Hospital Based Study among Glaucoma Patients to Assess Their Knowledge Regarding Various Aspects of Glaucoma

Introduction:Glaucoma is a chroniccondition and if not properly controlled will lead to blindness. So it is very important that patients on treatment for glaucoma should know about the course and outcome of the disease. Many patients stop the treatment because of treatment cost and also due to the prolonged treatment duration. Objectives: To find out the current level of knowledge of their disease among glaucoma patients attending a tertiary care hospital in south India.Methods: It was a cross sectional hospital-based study.Study participants included already diagnosed patients attending glaucoma clinic. A structured validated pretested questionnaire was given to collect data. The questionnaire was given to 320 patients attending glaucoma clinic during their routine visit. Grading was done based on the percentage of questions answered. Data were analyzed with SPSS version 18; (SPSS Inc; Chicago, IL)Results:The mean age was 59.34 ± 8. 86years.Femaleswere more aware compared to males. Only 40% (108) of patients knew that glaucoma can cause blindness. Socioeconomic factors had significant association only with awareness of the disease.Educational status had significant association with awareness about the disease as well as the treatment received. Disease duration did not have any significant association with awareness about glaucoma.Conclusion:Determinants of knowledge about glaucoma in this study were female gender, higher socioeconomic status and higher educational levels. Even glaucoma patients who are on treatment for glaucoma did not have sufficient knowledge about their disease.

Clinical Characteristics of Spinal Epidural Abscess Accompanied by Bacteremia.

ObjectiveThe treatment of choice for spinal epidural abscess (SEA) generally is urgent surgery in combination with intravenous antibiotic treatment. However, the optimal duration of antibiotic treatment has not been established to date, although 4–8 weeks is generally advised. Moreover, some researchers have reported that bacteremia is a risk factor for failure of antibiotic treatment in SEA. In this study, we investigated the clinical characteristics of SEA accompanied by bacteremia and also determined whether the conventional 4–8 weeks of antibiotic treatment is sufficient. MethodsWe retrospectively reviewed the medical records and radiological data of 23 patients with bacterial SEA who underwent open surgery from March 2010 to April 2020. All patients had bacteremia preoperatively and underwent weeks of perioperative antibiotic treatments based on their identified organisms until all symptoms of infection disappeared. All patients underwent microbiological studies of peripheral blood, specimens from SEA and concomitant infections. The mean follow-up duration was 35.2 months, excluding three patients who died. ResultsThe male : female ratio was 15 : 8, and the mean age was 68.9 years. The SEA most commonly involved the lumbar spinal segment (73.9%), and the mean size was 2.9 vertebral body lengths. Mean time periods of 8.4 days and 16.6 days were required from admission to diagnosis and from admission to surgery, respectively. Concomitant infections more frequently resulted in delayed diagnosis (p=0.032), masking the symptoms of SEA. Methicillin-sensitive Staphylococcus aureus was the most commonly identified pathogen in both blood and surgical specimens. Seventeen patients (73.9%) showed no deficits at the final follow-up. The overall antibiotic treatment duration was a mean of 66.6 days, excluding three patients who died. This duration was longer than the conventionally advised 4–8 weeks (p=0.010), and psoas or paraspinal abscess required prolonged duration of antibiotic treatment (p=0.038). ConclusionSEA accompanied by bacteremia required a longer duration (>8 weeks) of antibiotic treatment. In addition, the diagnosis was more frequently delayed in patients with concomitant infections. The duration of antibiotic treatment should be extended for SEA with bacteremia, and a high index of suspicion is mandatory for early diagnosis, especially in patients with concomitant infections.