Incidence Of Treatment Failure Research Articles

Rituximab Maintenance after First-Line Immunochemotherapy in Mantle Cell Lymphoma: Long-Term Follow-up of the Randomized European MCL Elderly Trial

Rituximab Maintenance after First-Line Immunochemotherapy in Mantle Cell Lymphoma: Long-Term Follow-up of the Randomized European MCL Elderly Trial

ISONIAZID MONORESISTANCE : THE NEW CHALLENGE IN DRUG RESISTANT TUBERCULOSIS

Background: Drug resistant tuberculosis is a global threat to overall tuberculosis control. Isoniazid is a critically important rst line drug. Isoniazid monoresistance increases the incidence of treatment failure and relapse. Method: A total of 100 sputum samples positive for acid fast bacilli by Ziehl-Neelsen staining were collected from pulmonary tuberculosis patients between September 2019 to January 2020 (four months) and subjected to Line probe assay (LPA). Result: Mycobacterium tuberculosis complex was detected in all the 100 samples by LPA. It was found that 82 (82%) samples were sensitive to both Isoniazid and Rifampicin, 9(9%) of them were multidrug resistant ,8(8%) were Isoniazid monoresistant and 1(1%) was Rifampicin monoresistant.Out of the Isoniazid monoresistance cases mutation in katG was seen in 87% cases and inhA mutation in 13%. Conclusion: Isoniazid resistance is surprisingly increasing and is missed out by rapid tests.

First-line antiepileptic drug treatment in glioma patients with epilepsy: Levetiracetam vs valproic acid.

ObjectiveThis study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first‐line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy.MethodsIn this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Maximum duration of follow‐up was 36 months.ResultsIn total, 776 patients using levetiracetam and 659 using valproic acid were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure for any reason was significantly lower for levetiracetam compared to valproic acid (12 months: 33% [95% confidence interval (CI) 29%–38%] vs 50% [95% CI 45%–55%]; P < .001). When looking at specific reasons of treatment failure, treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95% CI 12%–19%] vs 28% [95% CI 23%–32%]; P < 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95% CI 11%–18%] vs 15% [95% CI 11%–18%]; P = .636).SignificanceOur results suggest that levetiracetam may have favorable efficacy compared to valproic acid, whereas level of toxicity seems similar. Therefore, levetiracetam seems to be the preferred choice for first‐line AED treatment in patients with glioma.

Bibenzyl analogue DS-1 inhibits MDM2-mediated p53 degradation and sensitizes apoptosis in lung cancer cells

BackgroundLung cancer is a leading fatal malignancy due to the high incidence of treatment failure. Dysfunction of the tumor suppressor p53 contributes to cancer initiation, progression, and therapeutic resistance. Targeting MDM2, a negative regulator of p53, has recently attracted interest in cancer drug research as it may restore tumor suppressive function. PurposeThe present study aimed to investigate the effect of 3,4-dihydroxy-5,4′-dimethoxybibenzyl (DS-1) on targeting MDM2 and restoring p53 function in lung cancer cells. MethodsThe efficacy of DS-1 alone or in combination with cisplatin in lung cancer cells was determined by MTT, nuclear staining, and annexin V/PI assay. The expression of apoptosis-related proteins was determined by western blot analysis. To evaluate the role of DS-1 on the stabilization and degradation of p53, cycloheximide chasing assay and immunoprecipitation were conducted, and the active form of p53 was investigated by immunofluorescent staining assay. To confirm and demonstrate the site interaction between DS-1 and the MDM2 protein, in silico computational analysis was performed. ResultsDS-1 exhibited a cytotoxic effect and sensitized lung cancer cells to cisplatin-induced apoptosis. DS-1 caused a significant increase in the cellular level of p53 protein, while the active form of p53 (phosphorylation at Ser15) was unaltered. DS-1 treatment in combination with cisplatin could enhance activated p-p53 (Ser15) and p53 downstream signaling (Bax, Bcl-2, and Akt), leading to a higher level of apoptosis. Immunoprecipitation analysis revealed that DS-1 decreased the p53-ubiquitin complex, a prerequisite step in p53 proteasomal degradation. Molecular docking simulation further evidenced that DS-1 interacts with MDM2 within the p53-binding domain by carbon–hydrogen bond interaction at Lys27, π–alkyl interactions at Ile37 and Leu30, and van der Waals interactions at Ile75, Val51, Val69, Phe67, Met38, Tyr43, Gly34, and Phe31. Treatment by DS-1 and cisplatin in patient-derivated primary lung cancer cells showed consistent effects by increasing cisplatin sensitivity. ConclusionsOur findings provide evidence that DS-1 is an MDM2 inhibitor and its underlying mechanism involves MDM2 binding and p53 induction, which may benefit the development of this compound for lung cancer treatment.

Long-term Efficacy and Safety of Everolimus Versus Mycophenolate in Kidney Transplant Recipients Receiving Tacrolimus.

The short-term efficacy and safety of everolimus in combination with tacrolimus have been described in several clinical trials. Yet, detailed long-term data comparing the use of everolimus or mycophenolate in kidney transplant recipients receiving tacrolimus are lacking. This is a 5-y follow-up post hoc analysis of a prospective trial including 288 patients who were randomized to receive a single 3-mg/kg dose of rabbit antithymocyte globulin, tacrolimus, everolimus (EVR), and prednisone (rabbit antithymocyte globulin/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (basiliximab/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (basiliximab/mycophenolate, n = 101). There were no differences in the incidence of treatment failure (31.8% versus 40.2% versus 34.7%, P = 0.468), de novo donor-specific HLA antibodies (6.5% versus 11.7% versus 4.0%, P = 0.185), patient (92.9% versus 94.1% versus 92.1%, P = 0.854), and death-censored graft (87.1% versus 90.2% versus 85.1%, P = 0.498) survivals. Using a sensitive analysis, the trajectories of estimated glomerular filtration rate were comparable in the intention-to-treat (P = 0.145) and per protocol (P = 0.354) populations. There were no differences in study drug discontinuation rate (22.4% versus 30.4% versus 17.8%, P = 0.103). In summary, this analysis in a cohort of de novo low/moderate immunologic risk kidney transplant recipients suggests that the use of a single 3 mg/kg rabbit antithymocyte globulin dose followed by EVR combined with reduced tacrolimus concentrations was associated with similar efficacy and renal function compared with the standard of care immunosuppressive regimen.

An evaluation of antipseudomonal dosing on the incidence of treatment failure.

Introduction:Significant mortality is associated with delays in appropriate antibiotic therapy in Pseudomonas aeruginosa infections. The impact of empiric dosing on clinical outcomes has been largely unreported.Methods:This retrospective cohort compared treatment failure in patients receiving guideline-concordant or guideline-discordant empiric therapy with cefepime, meropenem, or piperacillin/tazobactam. Patients with culture-positive P. aeruginosa between 1 July 2013 and 31 July 2019 were eligible for inclusion. Patients with cystic fibrosis, polymicrobial infection, and urinary or pulmonary colonization were excluded. The composite primary outcome was treatment failure, defined as (1) therapy modification due to resistance/perceived treatment failure, (2) increased/unchanged qSOFA, or (3) persistent fever 48 h after initiating appropriate therapy. Secondary outcomes included rate of infectious diseases consultation, all-cause inpatient mortality, mechanical ventilation requirement, and infection-related intensive care unit and hospital lengths of stay.Results:In total, 198 patients were included: 90 guideline-concordant and 108 guideline-discordant. Baseline characteristics were balanced. Treatment failure was more common in the guideline-discordant than the guideline-concordant group (62% versus 48%; p = 0.04). This remained significant when adjusting for supratherapeutic dosing (p = 0.02). Infectious diseases consultation was higher in the guideline-discordant group (46% versus 29%, p = 0.01), while intensive care unit length of stay was longer in the guideline-concordant group (4.5 versus 3 days, p = 0.03). Additional secondary outcomes were similar.Conclusion:Treatment failure was significantly higher in patients receiving guideline-discordant empiric antipseudomonal dosing. Guideline-directed dosing, disease states, and patient-specific factors should be assessed when considering empiric antipseudomonal dosing.

Bacteriology and Antimicrobial Profile of Urinary Tract Infection in Adult Patients with Human Immunodeficiency Virus in a Nigerian Teaching Hospital

Introduction: There has been a rising incidence of treatment failures of Urinary Tract Infection (UTI) in patients with human Immunodeficiency Virus Infection (HIV). This study was carried out to determine the bacteriology of urinary tract infections in patients with HIV infections in University of Nigeria Teaching Hospital, Enugu. Methods: The study was a cross sectional study, involving 300 adult HIV positive patients, matched for age and sex with apparently healthy HIV negative subjects as control. Mid-stream urine samples from both groups were cultured on MacConkey, blood agar plates and incubated aerobically at 37°C. Antimicrobial susceptibility testing was done with agar diffusion method and interpreted according to CSLI guidelines. Extended spectrum beta-lactamases production was confirmed phenotypically using double disc synergy test. Results: The mean age of the subjects was 22.0 ± 3 years. There was a preponderance of females 76.0%. (P=0.493). The prevalence of UTI in the study group was 5.7% as against 2.7% in the control group. The most predominant bacteria isolated from study group were Escherichia coli (55.0%) with the least being Staphyloccocus saprophyticus (5.0%). In the control group only Escherichia coli (62.5%) and Klebsiella pneumoniae (37.5%) were isolated (r=0.973, P=0.005). Most of the organisms isolated were resistant to the commonly used antibiotics. Twenty percent (20.0%) of the Klebsiella pneumoniae and 14.0% of Escherichia coli isolated were ESBL producing.

Time to First-Line Antiretroviral Treatment Failure and its Predictors for Seropositive Children Treated in Public Hospitals, North West Ethiopia 2021

The magnitudes of Anti-Retroviral Treatment (ART) failure for adult people living with HIV (PLWH) were exhaustively studied; however, time to treatment failure among seropositive children was overlooked, and this study aimed to assess time to first-Line Antiretroviral treatment Failure for seropositive children. Methods: Facility-based retrospective follow-up study was conducted since 1 January 2016-30 December 2020. EPI- DATA version 3.2 and STATA/14 software were used for data entry and analysis, respectively. Proportional hazard assumption was checked for each variable and no variable was found with Schoenfeld residual test <0.05. Categorical variables at bi-variables Cox regression were assessed for candidates transferred at P-value <0.25 for multivariable Cox regression to claiming predictors associated for TB incidence rate at 95% CI at P<0.005. Results: A total of 710 recorded of ART files were reviewed with 96 children (13.5%) (95% CI: 11.2, 16.3) had developed treatment failures. The overall incidence rate of treatment failure was found 4.098 (95% CI: 3.35 to 5.02) per 1000 Person Month. Children being orphaned (AHR: 4.3, 95% CI: 2.17, 7.7), WHO stage III and IV (AHR: 3.5, 95% CI: 1.8, 7.4), Poor ART adherence 3.27 (AHR:3.27, 95% CI:1.54, 4.8), ART follow-up duration ≥ 72 months (AHR: 2.28, 95% CI: 1.2, 5.2), Missed CPT 6.7 (AHR-6.7; 95% CI: 3.6, 8.4), AZT-3TC-NVP 6.5 (AHR=6.5; 95% CI: 3.2, 18.2), AZT-3TC-EFV 2.9 (AHR=2.89, 95% CI: 2.89, 10.1) were associated with treatment failures. Conclusion: Sixty-two percent of treatment failures were occurred after 72 months of ART follow up with a higher incidence of treatment failures, which is unacceptable as compared with slandered reference <10%. Being a seropositive child ≥ 70 month on ART, WHO stage III and IV, ART regiment (AZT-3TC-NVP and AZT-3TC-EFV), Poor ART adherence, missing CPT, and orphanages were associated with treatment failure.

Treatment Failure and Associated Factors among Individuals on Second Line Antiretroviral Therapy in Eastern Uganda: A Retrospective Cohort Study.

Background:ART failure is a growing public health problem and a major threat to the progress of HIV/AIDS control. In Uganda however, little is documented on treatment outcomes and their associated factors among individuals on second line ART regimen. The rapid scale-up of ART over the past has resulted in substantial reductions in morbidity and mortality. However, as millions of people must be maintained on ART for life, individuals with ART treatment failure are increasingly encountered and the numbers are expected to rise. This could be attributed to factors such as sub-standard regimens, limited access to routine viral load monitoring, treatment interruptions, suboptimal adherence, among others. The purpose of this study was to estimate 5-year cumulative treatment failure and the associated factors among individuals on second line ART regimen Eastern Uganda.Materials and methods:A retrospective analysis of 541 records of HIV positive individuals, switched to second line ART regimen from January 2012 to December 2017. Inferential statistics including the Chi square test and multivariable logistic regression analysis was applied to determine associations of treatment failure against of the selected demographic, laboratory and clinical factors was performed. Associations between treatment failure and the predictors was based on a P-value of less than 5% and confidence intervals level of 95%.Results:We reviewed 541 records of individuals on second line ART regimen, of which 350 (64.7%) were female, 226 (41.8%) were married, and 197 (36.4%) were older than 35 years. The mean age at ART initiation was 30 years (SD = 14.8), while the mean weight at ART initiation was 47 kg (SD = 18.6), (range 4-97 kg). The overall proportion of treatment failure was 23%. The cumulative mortality risk for 5 years was 12.4% and the mortality rate was 2.5 deaths per 100 individuals per year. The odds of developing treatment failure among individuals switched to ATV/r-based regimen were 44% lower as compared to individuals who were switched to LPV/r (ORadj0.56, 95% CI 0.35-0.90, P = .016). while the odds of experiencing treatment failure among individuals that used AZT at ART initiation were 43% lower as compared to individuals that used a TDF based regimen at ART initiation (ORadj0.57, 95% CI 0.33-0.98, P = .041).Conclusion:The 5 year cumulative incidence of treatment failure in a cohort of 541 individuals was 23%. The type of protease inhibitor (PI) used in second line regimen and use of AZT at ART initiation were significantly associated with treatment failure. Our study also shows that the cumulative mortality risk while on second line ART regimen was 12.4% while the mortality rate was 2.5 deaths per 100 individuals per year. Given the high level of treatment failure among individuals on second line ART regimen, yet the current ART protocols limits the use of third line ART regimens to only regional referral hospitals, the Ministry of Health should strengthen the surveillance systems for identifying individuals failing on second line ART regimen even at district hospitals and lower health facilities to facilitate timely switch to optimal regimen. The Ministry of health through the Quality Improvement Division should conduct routine onsite support supervision to sites offering ART to ensure that treatment guides and other standard of care like timely switch to appropriate regimens among others are being adhered to. Knowledge gaps identified can also be addressed through onsite Continuous Medical Educations.

Methylprednisolone Pulse Therapy or Additional IVIG for Patients with IVIG-Resistant Kawasaki Disease.

There have been no robust data from clinical trials to guide the clinician in the choice of therapeutic agents for the child with intravenous immunoglobulin (IVIG) resistance. The treatment regimen for IVIG-resistant patients varies between institutions, and the best option has not yet been established. Therefore, in this trial, a total of 955 patients with Kawasaki disease (KD) were selected and were initially treated with IVIG (2 g/kg), of whom 80 (8.38%) assessed as IVIG resistant were randomly divided into two groups: Group A received the second IVIG treatment (n = 40), and Group B received methylprednisolone pulse therapy (MPT, n = 40). The whole fever time, duration of fever after retreatment, hospital days, medical costs, readmission rate, and laboratory examination difference (△) were calculated. Coronary artery lesion (CAL) outcomes were followed up over two years. Patients in the MPT group had shorter fever after retreatment and lower medical costs; more rapid declines in C-reactive protein (CRP), neutrophils (N%), and platelet (PLT) levels; and more rapid rise in sodium. However, they also probably had a higher incidence of treatment failure and CALs than the additional IVIG treatment group in the long-term follow-up. Caution is still required in the use of MPT to treat IVIG-resistant KD.

NCOG-45. FIRST-LINE ANTIEPILEPTIC DRUG TREATMENT IN GLIOMA PATIENTS WITH EPILEPSY: LEVETIRACETAM VERSUS VALPROIC ACID

Abstract BACKGROUND Levetiracetam and valproic acid are two of the most commonly prescribed antiepileptic drugs (AEDs) in patients with a glioma and epilepsy. This study aimed at estimating the cumulative incidence of treatment failure of first-line monotherapy levetiracetam versus valproic acid in glioma patients with epilepsy. METHODS In this retrospective observational study, a competing risk model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as competing event. Patients were matched on baseline covariates potentially related to treatment assignment and/or outcomes of interest according to the nearest neighbour propensity score matching technique. Secondary outcomes were the cumulative incidence of recurrent seizure, from AED treatment initiation (estimated with a competing risk model), and severity of adverse effects. Maximum duration of follow-up was 36 months. RESULTS In total, 776 patients using levetiracetam and 659 using valproic were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure (any reason) at 12 months for levetiracetam and valproic acid was equal to 33% (95%CI=29-38%) versus 50% (95%CI=45-55%), respectively (p&amp;lt; 0.001). The cumulative incidence of treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95%CI=12-19%] versus 28% [95%CI=23-32%]; p&amp;lt; 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95%CI=11-18%] versus 15% [95%CI=11-18%]; p=0.636). The cumulative incidence of recurrent seizure of levetiracetam was significantly lower compared to valproic acid (12 months: 54% [95%CI=49-59%] versus 67% [95%CI=62-71%]; p&amp;lt; 0.001). No significant differences were found for level of toxicity. CONCLUSION Our results suggest that levetiracetam has superior efficacy compared to valproic acid, while showing a similar level of toxicity. Therefore, levetiracetam seems the preferred choice for first-line AED treatment in glioma patients.

Efficacy of the levonorgestrel-releasing intrauterine device is associated with different subtypes of adenomyosis: a retrospective study.

BackgroundAlthough the levonorgestrel-releasing intrauterine device (LNG-IUD) has been widely applied in the treatment of adenomyosis, not all the patients are satisfied with its efficacy. The present retrospective study aimed to investigate the efficacy of LNG-IUD on different subtypes of adenomyosis.MethodsThe study comprised a cohort of 207 patients who received the LNG-IUD at the Women’s Hospital, Zhejiang University School of Medicine, China, from June 2013 to June 2016. Different subtypes of adenomyosis were classified by magnetic resonance imaging (MRI) and patients were subcategorized into three groups (subtype I: intrinsic, n=70; subtype II: extrinsic, n=73; subtype IV: indeterminate, n=64). Multiple variables were compared among the different groups.ResultsPatient demographics, clinical features and the treatment effects of the LNG-IUD were compared between the three subtype groups. The numeric rating scale (NRS) and pictorial blood loss assessment chart (PBAC) score markedly decreased after insertion of the LNG-IUD compared with baseline in all patients in the three subtype groups (P<0.001 for all groups). Compared to the other two subtypes, the efficacy rate was lower and the spontaneous expulsion rate was higher in subtype IV adenomyosis patients than that in other two groups (P<0.05). The independent factor associated with the spontaneous expulsion of the system was suggested to be uterine size before IUD placement and bleeding amount after LNG-IUD treatment in the subtype I [P=0.029, hazards ratio (HR): 3.37, 95% confidence interval (CI): 1.09–6.88] and IV (P=0.045, HR: 1.02, 95% CI: 1.01–1.21) adenomyosis patients respectively.ConclusionsThe LNG-IUD is proved to be an effective approach to treat subtype I and II adenomyosis. However, further study is warranted to explore a more suitable protocol to treat this subtype IV adenomyosis due to the high incidence of treatment failure and expulsion.

Randomized Trial of Amoxicillin for Pneumonia in Pakistan

BackgroundThe World Health Organization (WHO) recommends oral amoxicillin for patients who have pneumonia with tachypnea, yet trial data indicate that not using amoxicillin to treat this condition may be noninferior to using amoxicillin.MethodsWe conducted a double-blind, randomized, placebo-controlled noninferiority trial involving children at primary health care centers in low-income communities in Karachi, Pakistan. Children who were 2 to 59 months of age and who met WHO criteria for nonsevere pneumonia with tachypnea were randomly assigned to a 3-day course of a suspension of amoxicillin (the active control) of 50 mg per milliliter or matched volume of placebo (the test regimen), according to WHO weight bands (500 mg every 12 hours for a weight of 4 to <10 kg, 1000 mg every 12 hours for a weight of 10 to <14 kg, or 1500 mg every 12 hours for a weight of 14 to <20 kg). The primary outcome was treatment failure during the 3-day course of amoxicillin or placebo. The prespecified noninferiority margin was 1.75 percentage points.ResultsFrom November 9, 2014, through November 30, 2017, a total of 4002 children underwent randomization (1999 in the placebo group and 2003 in the amoxicillin group). In the per-protocol analysis, the incidence of treatment failure was 4.9% among placebo recipients (95 of 1927 children) and 2.6% among amoxicillin recipients (51 of 1929 children) (between-group difference, 2.3 percentage points; 95% confidence interval [CI], 0.9 to 3.7). Results were similar in the intention-to-treat analysis. The presence of fever and wheeze predicted treatment failure. The number needed to treat to prevent one treatment failure was 44 (95% CI, 31 to 80). One patient (<0.1%) in each group died. Relapse occurred in 40 children (2.2%) in the placebo group and in 58 children (3.1%) in the amoxicillin group.ConclusionsAmong children younger than 5 years of age with nonsevere pneumonia, the frequency of treatment failure was higher in the placebo group than in the amoxicillin group, a difference that did not meet the noninferiority margin for placebo. (Funded by the Joint Global Health Trials Scheme [of the Department for International Development, Medical Research Council, and Wellcome] and others; RETAPP ClinicalTrials.gov number, NCT02372461.)

Ventriculo-peritoneal shunting devices for hydrocephalus.

Ventriculo-peritoneal shunting devices for hydrocephalus.

Efficacy of Almitrine in the Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome

Efficacy of Almitrine in the Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome

Incidence, treatment, and outcomes of primary and recurrent Non-Wilms renal tumors in children: Report of 109 patients treated at a single institution

Non-Wilms renal tumors represent a compelling subset of childhood renal tumors. However, their relative rarity renders accurate diagnosis, and therapy challenging which in some instance is inferred from their adult counterparts. To describe the incidence and analyze the diagnostic challenges, therapies and, outcomes of non-Wilms renal tumors at the largest tertiary cancer centre in India. All patients with histologically confirmed non-Wilms renal tumours diagnosed in the paediatric oncology unit of Tata Memorial Hospital between 2006 and 2019 were included. Data regarding clinical and radiological features and treatment outcomes were retrieved from the prospectively maintained institutional database. At the outset, histological types were categorised into a high and low-risk group depending on anticipated survival. Survival analysis was performed utilising the Kaplan-Meier method on SPSS software version 24.0. Of the 569 patients with renal tumors, 109 (19%) patients with primary (n=97) or recurrent (n=12) non-Wilms renal tumors were included. Histological high-risk group included clear cell sarcoma (CCSK) (39.4%), renal cell carcinoma (RCC) (19.3%), malignant rhabdoid tumor (MRTK) (12.8%), Ewing's sarcoma (rES) (15.6%), synovial sarcoma (2%), and undifferentiated sarcoma (2%). The low-risk group comprised of congenital mesoblastic nephroma (CMN) (4.6%), cystic partially differentiated nephroblastoma (2%), and other rare tumors (3%). Diagnostic error occurred in 2 patients in the high-risk group. All low-risk tumours were treated with surgery alone and most (97%) high-risk tumors were operated either upfront (61.5%) or after preoperative chemotherapy (38.4%). Adjuvant therapy based on histology was offered to 70%. The recurrent tumors received various salvage treatments including chemotherapy; radiotherapy; surgery and immunotherapy, however, only 2 patients could be salvaged. The 3-year overall survival for the entire cohort with primary tumors was 59%, and the survival rates were 76.7%, 77.9%, 0.0%, and 52% for CCSK, RCC, MRTK, and rES (summary figure). Low-risk tumors had 100% survival while the recurrent tumors had a median survival of 10.5 months. Non-Wilms renal tumors constitute a heterogeneous group of tumors, accounting for less than 20% of all renal tumors. Low-risk tumors are associated with excellent outcomes following surgery alone while the high-risk tumours have a variable outcome. MRTK and recurrent non-Wilms tumour have the worst survival. Favourable outcomes for CCSK and RCC and worst outcomes for MRTK were observed in this study. Renal ES have higher incidence of treatment failure and unsatisfactory outcomes. Recurrent non-Wilms tumours have an extremely poor outcome and more alternative or innovative approaches are needed for their treatment.

MON-LB58 The Use of 11C Methionine PET CT In Localization of ACTH Dependent Cushing’s Disease

Background and objective: Hypercortisolism is the hall mark of ACTH Cushing’s syndrome, which is a benign ACTH secreting tumor resulting in high morbidity and mortality. The diagnosis is based on an elevated serum ACTH, elevated 24h urinary cortisol or a non-suppressible ACTH after dexamethasone suppression test. Confirmation of ACTH hypersecretion is followed by localization of the adenoma which can be pituitary in origin or peripheral. Dynamic MRI of the pituitary gland is the gold standard for diagnosis of pituitary tumors, and contrast enhanced CT scan is the gold standard for ectopic lesions which are usually lung tumors. The localization of the lesion is often a challenge because conventional MRI fail to show pituitary lesions and sometimes requiring inferior petrosal sinus sampling to confirm pituitary origin. Transsphenoidal surgery is the treatment of choice for Cushing’s disease, even without MRI evidence of pituitary tumors, if pituitary origin is confirmed by inferior petrosal sinus sampling. This causes increase in the incidence of treatment failure and complications. Thus, the diagnosis of Cushing’s disease urges exploring new diagnostic modalities. In our study we test the sensitivity of 11C methionine PET CT together with dynamic pituitary MRI in localization of ACTH dependent Cushing’s disease. Materials and methods This is an interventional, prospective study, forty-one subjects: newly diagnosed ACTH dependent Cushing’s Syndrome (n=29). (indicated by non-suppressible ACTH on dexamethasone suppression test) or persistent hypercortisolism following transsphenoidal surgery (n=12). 11C methionine PET CT was done in all cases in addition to dynamic pituitary MRI. All patients underwent 11 C-methionine PET-CT in addition to dynamic pituitary MRI This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging.Inclusion Criteria:• Aged 18 years old or over• Patient with a diagnosed Cushing’s disease confirmed by non-suppressible ACTH on dexamethasone suppression test.• Patient with persistent ACTH dependent Cushing’s disease following transsphenoidal surgery.• Patient not enrolled in other interventional studies.Exclusion Criteria:• Contraindication to MRI• Pregnant woman, breastfeeding RESULTS: Patients with newly diagnosed ACTH dependent Cushing: 24 out of 29 of the cases showed adenoma on dynamic MRI of the pituitary; 5 out of 29 cases failed to showed any lesions on dynamic MRI of the pituitary; Inferior petrosal sampling was done and confirmed pituitary origin in 4 out of 5 and 1 out of 5 was found to have ectopic ACTH secretion. In patients with persistent hypercortisolism following transsphenoidal surgery; 3 out of 12 of the cases showed adenoma on dynamic MRI of the pituitary and 7 out of 12 cases failed to showed any lesions on dynamic MRI of the pituitary and inferior petrosal sampling was done and confirmed pituitary origin in all 12 cases. All 41 cases underwent 11C methionine PET CT scan; 39 patients showed tracer uptake on 11c methionine PET CT scan in the pituitary area, 36 of which had unilateral asymmetrical tracer uptake. All 40 subjects with suspected pituitary lesions were confirmed to be of pituitary origin by histopathological examination of biopsies taken intraoperatively. CONCLUSIONS 11C methionine PET CT has proven to be of very high sensitivity in detecting ACTH secreting adenomas, further studies should be done on a larger scale as this modality can address the pitfalls in localization of ACTH secreting lesions.

Vaccinomics strategy to concoct a promising subunit vaccine for visceral leishmaniasis targeting sandfly and leishmania antigens

Visceral leishmaniasis (VL) has been declared as one of the most severely neglected tropical diseases by the World Health Organization report 2017. Cumulative incidences of treatment failure and drug resistance, demanding a potential treatment and preventive strategy for VL. In this study, we have devised a multi-epitope vaccine by targeting sandfly saliva and parasite-derived membrane and secretory antigens. We have predicted the immunogenic B-cell, HTL, and CTL epitopes from all the selected protein sequences. The epitopes were then linked to the spacer sequences for providing stability and flexibility, and the construct was linked with a synthetic TLR-4 agonist namely RS09 as an adjuvant. The 3D structure of vaccine was modelled, refined and validated by generating a Ramachandran plot. Later, molecular docking was performed between the TLR-4 receptor and vaccine. The obtained docked complex was then checked for their stability by performing MD simulation. The immune dynamics simulation was done to check the probable immune response generated when the host will be exposed to the vaccine candidate. This novel vaccine strategy will provide functional and mechanistic evidence on parasite and vector-derived epitopes that could activate B- and T-cells and potentially elicit a long-lasting memory cell response.

Laparoscopic Heller myotomy or pneumatic dilatation in achalasia: results of a prospective, randomized study with at least a decade of follow-up.

The most efficient long-term treatment strategy for achalasia has yet to be established. This study compared the long-term results (≥ 10years) after either pneumatic dilatations or laparoscopic myotomy using treatment failure as the primary outcome. Secondary objectives were; the frequency and degree of dysphagia and effects on health-related quality of life (QoL). Out of the 53 patients with achalasia who were initially randomized to either laparoscopic myotomy with a posterior partial fundoplication (LM) or repetitive pneumatic dilatation (PD), 43 remained for scrutiny after a median observation period of 170months (LM; n = 20 and PD; n = 23). At the follow-up of 60months, 10 patients (36%) in the PD group and two patients (8%) in the LM group were classified as treatment failures (p = 0.016). At the latest follow-up time point (≥ 10years), the corresponding numbers were 13 (57%) and 4 (20%), respectively. The Kaplan-Meier analysis of the cumulative incidence of treatment failure revealed a significant advantage of LM over the dilatation strategy (p = 0.036)). QoL assessed by the generic instrument PGWB and the more disease-specific instrument GSRS revealed scores which were similar in the two study groups with no obvious changes over time. Reflux was better controlled in the LM group (p = 0.02 regarding PPI consumption). After more than a decade of follow-up, laparoscopic myotomy reinforces its superiority over repetitive pneumatic dilatation treatment strategy in the management of newly diagnosed achalasia.

The role of multidrug and extensive-drug resistant Gam-negative bacteria in skin and soft tissue infections.

Whereas Staphylococcus aureus remains the leading cause of skin and soft tissue infections (SSTI), Gram-negative bacilli (GNB) are increasingly reported as a cause of monomicrobial or polymicrobial infections. This review examines the expanding role of GNB in SSTI and discusses the risks for and the frequency of multidrug-resistance (MDR) and extensive drug-resistance (XDR) and the implications with regard to outcome and therapy. Although the global epidemiology and role of GNB in SSTIs have not been studied systematically, complicated SSTIs caused by resistant GNB are increasing particularly in vulnerable patients with long-standing infections, those in long-term care facilities, and those with a history of recent hospitalization or prior antibiotic therapy. Mixed infections also occur in up to 25% of SSTIs, and inappropriate therapy occurs in 40% of cases. Prompt identification of the causative pathogen requires that patients with SSTI be risk stratified according to the likelihood of resistance to enable early recognition and swift initiation of appropriate therapy. For individual treatment decisions in SSTIs, institutional diagnostic and treatment algorithms based on local epidemiology and risk factors are pivotal to reducing the incidence of treatment failure and improving outcomes associated with resistant GNB.