Short Course Of Dexamethasone Research Articles

OEIS Syndrome: Omphalocele, Exstrophy of the Cloaca, Imperforate Anus, and Spinal Defects

OEIS Syndrome: Omphalocele, Exstrophy of the Cloaca, Imperforate Anus, and Spinal Defects

Difficulties in differential diagnosis of cutaneous manifestations in patients with coronavirus infection

Patients with severe SARS-CoV-2 infection (COVID-19) and multiple comorbidities should be monitored for possible adverse reactions to prescribed drugs, including drug eruptions (DE) at any stage of treatment. Below, we describe a clinical case of a 92-year-old female patient with severe PCR-confirmed COVID-19. The patient was treated with amoxicillin/clavulanic acid, moxifloxacin, acetylcysteine, and sodium enoxaparin. On day 9 into treatment, the patient developed moderately itching macular rashes showing a tendency to coalesce, but overall showed no signs of deterioration. On day 15, the rashes regressed, following a short course of dexamethasone and chloropyramine. This kind of skin reaction might have been provoked by β-lactams and fluoroquinolones included in the treatment regimen, a secondary bacterial infection, compromised immunity due to advanced age, and high viral load associated with dermatological symptoms. Delayed onset of skin symptoms might be regarded as a marker of COVID-19 severity.

Duration of dexamethasone administration for the prevention of chemotherapy-induced nausea and vomiting - A systematic review and meta-analysis.

Chemotherapy-induced nausea and vomiting (CINV) is the most common non-haematological toxicity of chemotherapy. A systematic review and meta-analysis comparing short course (1-2 days) with long course (3+ days) dexamethasone in preventing CINV was performed in accordance with the PRISMA statement. 1535 articles were screened to identify the 11 studies included in the review. Nine studies of 1892 patients were included in meta-analysis. There was no significant difference in complete response of nausea and vomiting between a short or long course of dexamethasone (RR 0.98, 95 % CI 0.89-1.07, p = 0.58). There was a lower risk of adverse events with a short course of dexamethasone (RR 0.80, 95 % CI 0.64-0.99, p = 0.04). There was no significant difference between a short or long course of dexamethasone in preventing nausea or vomiting, but a short course was associated with fewer adverse effects. PROSPERO protocol: CRD42019133785.

Dexamethasone versus prednisone for children receiving asthma treatment in the paediatric inpatient population: protocol for a feasibility randomised controlled trial

IntroductionAsthma exacerbations are a leading cause of paediatric hospitalisations. Corticosteroids are key in the treatment of asthma exacerbations. Most current corticosteroids treatment regimens for children admitted with asthma exacerbation consist...

Immunotherapy in lymphoma.

Immunotherapy in lymphoma.

Dexamethasone Reduces Incidence of Relapse and Improves Overall Survival in Hyperleucocytic Acute Myeloid Leukemia

Patients with AML and hyperleukocytosis (HL) are at increased risk for early death and relapse. HL is associated with a leukostasis syndrome that can potentially lead to acute respiratory distress syndrome or strokes. HL is independently associated with a shorter RFS (Rollig C, Blood 2015). Mediators of inflammation induced by leukemic blasts and endothelial cells contributed to the pathogenesis of leukostasis and could induce chemoresistance (Stucki A, Blood 2001). We hypothesized that a short course of Dexamethasone (DEX) at induction chemotherapy could improve outcome of HL AML pts.From Jan 2004 to Dec 2013, 662 pts (18-75y) were treated in our center by intensive chemo: dauno (60-90 mg/m² d1-3) or idarubicin (8 mg/m² d1-5) with AraC (100-200 mg/m² d1-7); lomustin 200 mg/m² (d1) being added in patients >60y. Hydroxyurea (HU) could be started promptly at diagnosis. Leukapheresis were not performed. Starting from Jan 2010, DEX 10 mg bid d1-3 was systematically added on the chemo backbone of all pts with a WBC > 100 x109/L or 50 x109 /L with leukostasis. Supportive care was given according to standard guidelines that did not change across the study period. This retrospective study included 137 patients with WBC >50 x109 /L.The median age was 59.7y (47% ≥60y). Median FU was 4.2 years. 49 pts received DEX and were more likely to have poorer PS, leukostasis syndrome, de novo AML and higher WBC count compared to the 88 pts of the non-DEX group whereas cytogenetics risk and ELN classification were similar. HU was given in 27 pts of the DEX group and in 51 pts of the non-DEX group. AlloSCT was performed in 14 pts of the DEX group and in 19 pts of the non-DEX group.CR rate were 78% (DEX) and 74% (no-DEX), respectively (p=0.357). At d60, 7 pts (14%) had died in the DEX group compared to 17 pts (19%) in the no-DEX group (p=0.457). There were no difference in fungal (p=0.351) or bacterial (p=0.96) infections during induction. There were more grade 3-4 bleeding events (18% vs 7%, p=0.038) and more admissions in ICU (31% vs 15%, p=0.028) in the DEX group. DEX significantly improved DFS (HR 0.41; 95% CI, 0.23-0.74, p=0.003) and OS (HR 0.62; 95% CI, 0.39-0.99, p=0.046) (Figure). In a Fine and Gray model, DEX was associated with a lower risk of relapse (aHR ratio 0.13; 95% CI, 0.05-0.33, p<0.001). In Cox proportional hazards models, DEX was associated with a better DFS (aHR, 0.22; 95% CI, 0.10 to 0.48, p<0.001). An interaction was found between DEX and both the period of treatment (2004-2009 vs2010-2013) and the genetic classification when considering OS meaning that DEX significantly improved OS in patients with intermediate cytogenetic risk and NPM1 mutations especially during the latest period (aHR, 0.07; 95% CI, 0.02 to 0.22, p<0.001).Because of the statistical interaction with NPM1 mutations, we hypothesized that NPM1mut-AML might be particularly sensitive to DEX. Interrogation of transcriptomic data set (Verhaak RG, Haematologica 2009) and data mining algorithm revealed that the NPM1 mutation signature is highly enriched in genes responsive to DEX. OCI-AML3 (NPM1/ DNMT3A mutated) was one of the most sensitive cell line and NPM1mut-AML samples (n=16) were more sensitive to apoptosis induction by DEX compared to non-NPM1mut samples (n=18). Further transcriptomic analyses with TCGA data set (NEJM 2013) revealed more complex molecular interactions between AML subgroups and DEX (DNMT3A, RUNX1 mutations, CBFB-MYH11A were predicted to be responsive). In NSG mice xenografted with OCI-AML3, the combination of DEX+AraC significantly improved mice survival compared to AraC alone (p=0.0001). Lastly, in a PDX-NSG model of chemoresistance (Aroua N, ASH 2015), transcriptomic analyses of in vivo AraC-resistant leukemic cells (after 5 daily doses of 60mg/kg) showed a strong up regulation of genes involved in immune and inflammatory response (including NF-kB network) and a highly significant interaction with DEX-modulated genes suggesting that DEX could downregulate inflammatory pathways responsible for in vivo chemoresistance.DEX improves outcome of AML pts treated by chemotherapy by reducing the risk of relapse. The impact of DEX has been adjusted on several factors to limit biases inherent to non-randomized studies and a strong biological rationale was provided to strengthen the clinical finding. Thus, this finding could be easily translated in routine practice by adding DEX to chemotherapy at least for HL AML pts and/or NPM1 mutations. [Display omitted] DisclosuresRécher:Celgene, Sunesis, Amgen, Novartis, Chugai: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Tavitian:Novartis: Membership on an entity’s Board of Directors or advisory committees. Vergez:Novartis: Research Funding. Huguet:Pfizer, Novartis, BMS, Ariad, Jazz, Amgen: Membership on an entity’s Board of Directors or advisory committees. Sarry:GSK, Novartis: Research Funding.

Which Came First: A Rare Take on the Sarcoidosis-Lymphoma Syndrome

Which Came First: A Rare Take on the Sarcoidosis-Lymphoma Syndrome

A59: Dexamethazone Therapy for Septic Arthritis in Children: a Follow Up Study

Background/Purpose:In our previous prospective study we have demonstrated that the administration of Dexamethasone as an adjuvant therapy lead to a significant clinical and laboratory improvement in children with septic arthritis. This therapy has become accepted in some of the pediatric wards at Schneider's medical center. The aim of this study was to evaluate the effect of adding Dexamethasone to antibiotic therapy on the clinical course of septic arthritis in children not under controlled study.Methods:A retrospective study included all children hospitalized with the diagnosis of septic arthritis at Schneider Children's Medical Center from 2008–2013 .Part of the patients were treated with antibiotics alone, whereas others were treated with Dexametasone in addition to antibiotics, according to the policy of the admitting ward.Results:116 medical records were included in our study. Of which, 26 (22.4%) patients were treated with Dexamethasone and antibiotics and 90(77.6%) were treated with antibiotics only. There was no significant difference between the groups in age, duration of symptoms prior to hospitalization, body temperature or levels of acute phase reactants. Bacteria were isolated from 23 patients (20%) without any difference between the two groups. Patients treated with Dexamethasone had a significantly shorter duration of fever (mean 1st day without fever 2.3 vs. 3.9) (p = 0.002), shorter duration of parenteral antibiotic treatment (mean of 7.1 vs. 11.4 days) (p &lt; 0.001) and accelerated clinical improvement (mean 1stday without pain or any limitation in physical examination 6.3 vs. 10 days)(p&lt;0.001).Likewise, C‐reactive protein (CRP) levels declined faster below 1mg/dL in the Dexamethasone group (mean of 5.3 vs. 8.4 days) (p = 0.002) and the hospital stay was significantly shorter (mean of 8 vs. 10.7 days) (p = 0.004). No side effects of treatment were recorded in either group, but in the Dexamethasone group a short rebound of symptoms occurred in 3/26 (11.5%) patients after completing the course of steroids.Conclusion:A short course of Dexamethasone given early, in addition to antibiotics, leads to a significant clinical and laboratory improvement, shortens duration of treatment and accelerates recovery in children with septic arthritis.

EPA-1257 – Acute onset of manic episode induced by dexamethasone in a patient with atopic dermatitis

The corticosteroid-induced neuropsychiatric symptoms may occur at any time of corticosteroid use and include depression, mania, psychosis and delirium. To present corticosteroid-induced neuropsychiatric symptoms of patient with atopic dermatitis. A case report of acute manic episode induced by a short course of dexamethasone. A thirty-six year old female was referred to the Department of Dermatology and Venereology, Medical University of Lodz because of insufficient clinical improvement of a treatment regimen ordered, and due to psychiatric problems associated with the use of dexamethasone. History of any other skin disease, psychiatric problems or internal disorder was not relevant. After two days of treatment with dexamethasone 8 mg, the patient developed progressively increasing symptoms of psychomotor agitation, elevated mood, distractibility and early waking up. Six days later she started to experience increasing sensitivity to acoustic stimuli, startle response, feeling of being almighty and anxiety. On the ninth day dexamethasone was withdrawn. After a psychiatric consultation she was prescribed sodium valproate from 75 mg to 300 mg. The patient was also taking perazine 25 mg in the evening together with valproate. All the symptoms resolved two weeks after administration of antipsychotic treatment. Understanding the neurobiological mechanism involved in glucocorticoid-induced affective disorders is crucial for effective prevention and treatment of these complications. Further studies are needed to elucidate if patients with atopic dermatitis represent a special risk group considering psychiatric complications of systemic steroid treatment.

English

A 30 year old Indian woman presented to the ObGy Department with history of amenorrhea for two years associated with progressively increasing hirsuitism, clitoral hypertrophy and generalised hyperpigmentation of skin all over her body. On evaluation her serum testosterone was found to be elevated (403ng/dl). Endocrine evaluation revealed glucose intolerance and a mild elevation in ACTH. CT Scan of the Abdomen and Pelvis revealed mildly enlarged ovaries bilaterally and normal adrenal gland anatomy. In view of an ovarian pathology she underwent wedge resection of both ovaries and histopathology of the ovaries was reported as ovarian hyperthecosis. Postoperatively she was given an antiandrogen flutamide and a short course of dexamethasone following which she resumed her menstrual function within 2 months and showed a improvement in androgenic symptoms after 6 months. Hence Wedge resection of ovaries followed by antiandrogens and corticosteroids postoperatively is an effective method of treating hyperandrogenic symptoms.

A TLR and Non-TLR Mediated Innate Response to Lentiviruses Restricts Hepatocyte Entry and Can be Ameliorated by Pharmacological Blockade

Lentiviral vector (LV)-mediated gene transfer is a promising method of gene therapy. We previously reported that systemic injection of HIV-based LV triggers a transient inflammatory response. Here, we carried out studies to better characterize this response, and to develop a strategy to overcome the adverse effects of interferon (IFN) on LV-mediated gene transfer. We profiled gene expression in the liver after LV administration using deep-sequencing (RNA-seq), and identified several innate response pathways. We examined the response to LV in MyD88-TRIF knockout mice, which are incapable of toll-like receptor (TLR) signaling. Unexpectedly, the IFN response to LV was not reduced in the liver indicating that a non-TLR pathway can recognize LV in this organ. Indeed, blocking reverse transcription with azidothymidine (AZT) reduced the IFN response only in the liver, suggesting that proviral DNA can be a trigger. To block the inflammatory response, we pretreated mice with a short course of dexamethasone (Dex). At 4 hours post-treatment, all the IFN-induced genes were normalized. By blocking the inflammatory response, hepatocyte transduction was dramatically increased, which in turn doubled the level of human factor IX (FIX) produced by a hepatocyte-specific LV. Our studies uncover new insights into LV-induced immune responses in the liver, and provide a means to increase the safety and efficiency of LV-mediated gene transfer.

Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

BackgroundBrainstem metastases represent an uncommon clinical presentation that is associated with a poor prognosis. Treatment options are limited given the unacceptable risks associated with surgical resection in this location. However, without local control, symptoms including progressive cranial nerve dysfunction are frequently observed. The objective of this study was to determine the outcomes associated with linear accelerator-based stereotactic radiotherapy or radiosurgery (SRT/SRS) of brainstem metastases.MethodsWe retrospectively reviewed 38 tumors in 36 patients treated with SRT/SRS between February 2003 and December 2011. Treatment was delivered with the Cyberknife™ or Trilogy™ radiosurgical systems. The median age of patients was 62 (range: 28–89). Primary pathologies included 14 lung, 7 breast, 4 colon and 11 others. Sixteen patients (44%) had received whole brain radiation therapy (WBRT) prior to SRT/SRS; ten had received prior SRT/SRS at a different site (28%). The median tumor volume was 0.94 cm3 (range: 0.01-4.2) with a median prescription dose of 17 Gy (range: 12–24) delivered in 1–5 fractions.ResultsMedian follow-up for the cohort was 3.2 months (range: 0.4-20.6). Nineteen patients (52%) had an MRI follow-up available for review. Of these, one patient experienced local failure corresponding to an actuarial 6-month local control of 93%. Fifteen of the patients with available follow-up imaging (79%) experienced intracranial failure outside of the treatment volume. The median time to distant intracranial failure was 2.1 months. Six of the 15 patients with distant intracranial failure (40%) had received previous WBRT. The actuarial overall survival rates at 6- and 12-months were 27% and 8%, respectively. Predictors of survival included Graded Prognostic Assessment (GPA) score, greater number of treatment fractions, and higher prescription dose. Three patients experienced acute treatment-related toxicity consisting of nausea (n = 1) and headaches (n = 2) that resolved with a short-course of dexamethasone.ConclusionSRT/SRS for brainstem metastases is safe and achieves a high rate of local control. We found higher GPA as well as greater number of treatment fractions and higher prescription dose to be correlated with improved overall survival. Despite this approach, prognosis remains poor and distant intracranial control remains an issue, even in patients previously treated with WBRT.

Stereotactic Radiosurgery for the Treatment and Palliation of Skull Base Metastases

Objective: We herein report the role of stereotactic radiosurgery (SRS) in the management of symptomatic skull base metastases. Design: This institutional series reviewed 18 consecutive patients with a total of 21 skull base metastases identified between January 2001 and December 2011. Patients/Materials and Methods: The average age of the population was 60.5 years old, presenting on average 4.5 years following initial diagnosis of visceral disease. Most patients presented with symptomatic disease including pain and specific cranial nerve involvement including trigeminal (3), abducens (1), facial (2), and vestibulocochlear (3) nerves. The median treatment volume was 9.7 cc, receiving a median prescribed dose of 20 Gy (range, 15–40 Gy) delivered in 1 to 5 fractions. Results: Of the 18 patients, 10 succumbed to extensive metastatic disease before the first imaging evaluation. Clinical and imaging follow-up was available for the eight remaining patients, of which three had local failure at 1.2, 2.5, and 5.4 months following treatment. In regards to palliation, six of the patients had significant cranial nerve deficits, of which five reported improvement in symptoms. Additionally, all five patients with pretreatment pain reported improvement. At the time of this analysis, 15 of 18 patients have died; however, only one succumbed from progressive CNS disease. One patient reported an increase in paraesthesia and periorbital edema, which improved with a short course of dexamethasone. Conclusions: SRS is a safe and potentially effective treatment for skull base metastases with acceptable rates of local control and palliation of symptoms.

Changes in serum cortisol levels during community-acquired pneumonia: The influence of dexamethasone

In community-acquired pneumonia (CAP), the cortisol level on admission can be a useful biomarker for prognosis. Serial cortisol measurements during the clinical course of disease and their association with disease outcome have never been reported. Furthermore, the time to recovery of the hypothalamic-pituitary-adrenal axis after a short course of dexamethasone during infection is unclear. We analyzed data from 270 hospitalized patients with CAP. Total serum cortisol was measured on presentation, day 1, 2, 4, and on control visit (day 30). Intensive care unit (ICU) admission and mortality were assessed. Additionally, to study the influence of dexamethasone on the kinetics of the cortisol response, we analyzed serial cortisol values of 43 patients treated with a four-day regimen of dexamethasone 5 mg. During hospital stay, 26/270 patients (9.6%) were admitted to the ICU and 15/270 patients (5.6%) died. Compared to patients with an uneventful recovery, cortisol on presentation was significantly higher in patients with an adverse outcome (360 μg/L, IQR 209-597 vs. 238 μg/L, IQR 151-374) (p:0.01), and also remained significantly higher throughout the course of disease. Dexamethasone treatment resulted in nearly complete suppression of the endogenous cortisol production after the first dose, but cortisol production was fully recovered on control visit. In conclusion, we showed that an adverse outcome of CAP was associated with persisting higher total serum cortisol throughout the course of disease. Delta-cortisol could be another meaningful biomarker in CAP. Next, our data indicate that a four-day dexamethasone regimen during CAP does not lead to prolonged secondary adrenal insufficiency.

Streptococcus suisMeningitis without History of Animal Contact, Italy

<i>Streptococcus suis</i>Meningitis without History of Animal Contact, Italy

The Effects of Induction Chemotherapy and High-Dose Melphalan with Tandem Autologous Transplantation in Multiple Myeloma: The Prospective Randomized DSMM 2 Study.

The concept of the DSMM 2 study was to give age-adjusted high-dose treatment to elderly myeloma patients in order to balance efficacy and toxicity. The value of conventional induction chemotherapy before high-dose melphalan and autologous stem cell transplantation and the durability of unmaintaned remissions afterwards was addressed. Between September 2001 and September 2006, 434 multiple myeloma patients 60–70 years of age with 0–1 cycle of pretreatment were recruited from 45 centers. The median age was 65 years. The patients were randomized to receive 4 cycles of conventional induction chemotherapy [A1] (n=216; VAD or idarubicin/Dex in 88%) or no induction chemotherapy [A2] (n=218). Instead of induction chemotherapy, patients in [A2] received only one short course of dexamethasone 40 mg orally (days 1–4 and 8–11). Subsequently, stem cells were mobilized after combination chemotherapy with ifosfamide, epirubicin and etoposide (IEV) followed by G-CSF; stem cells could be collected in 97% of the patients. Then the patients proceeded to tandem MEL140 (melphalan 140 mg/m2) and autologous peripheral blood stem cell transplantation with a time interval between high-dose cycles of 2 months. No consolidation or maintenance treatment was scheduled. Analyses were performed in an intent-to-treat approach. 87% of patients completed the first transplant, 74% the second. Overall, the treatment was well tolerated and grade 3/4 infections and stomatitis after high-dose melphalan occurred in 37% and 9% of patients, respectively. The overall mortality (tumor and/or toxicity) during treatment was 7.1%: 4.5% during the induction phase (6.1% in [A1] versus 2.9% in [A2]), 1.5% after mobilization and 1.1% after high-dose therapy. Notably, the best response (EBMT criteria) at the end of treatment in patients randomized to [A1] (16% CR, 64% PR) or [A2] (18% CR, 69% PR) was not different. An early loss of tumor control with disease progression occurred in 6% in [A1] versus 1% in [A2]. With a median follow-up time of 20 months, there was no significant difference in the median event-free survival (EFS) (22 months in [A1] versus 20 months in [A2]) and not in the overall survival (OS) at 4 years (63% in [A1] versus 65% in [A2]). In ≥ 50% of patients, the time between last treatment and progression was > 16 months. The EFS of patients 60–64 years of age and 65–70 years of age was the same. In conclusion, there was no benefit of conventional induction chemotherapy with VAD- or VAD-like regimens in patients receiving tandem MEL140 with autologous transplantation. This induction treatment therefore may be avoided. Tandem-MEL140 is feasible and well tolerated in the majority of elderly patients with symptomatic myeloma. Its profound and durable anti-tumor effect was demonstrated by prolonged unmaintained remissions. The addition of new agents given as consolidation or maintenance probably will further improve treatment results.

Avascular Necrosis of Head of Femur in a Patient with Acute Promyelocytic Leukemia

Avascular necrosis (AVN) of head of the femur is associated with various pathological conditions and treatment modalities. We present a case of acute promyelocytic leukemia who was treated with all-transretinoic acid (ATRA), daunomycin, cytarabine and a short course of dex-amethasone. He developed AVN of bone after 2 years of treatment. Whether this is related to ATRA is dealt with in the discussion.