Course Of Dexamethasone Research Articles

Long-term survival by surgery and adjuvant chemotherapy in a patient with perforated extranodal NK/T-cell lymphoma of the small intestine: a retrospective case study

BackgroundExtranodal natural killer/T-cell lymphoma, nasal type (ENKL) of the small intestine, is a disease with extremely poor prognosis. We describe treatment in a case which is novel in that it demonstrated long-term survival.Case presentationA 68-year-old man was admitted to the emergency department of our hospital with the complaint of severe umbilical pain with tenderness and muscular defense. An abdominal computed tomography scan revealed a thick-wall mass on the small intestine and intra-abdominal free air. He was suspected of perforation of a small intestinal tumor and underwent emergency surgery. The surgery revealed a perforated tumor ulcer, and ENKL was diagnosed from the postoperative pathological findings. The patient’s postoperative course was uneventful. He was further treated with adjuvant chemotherapy by hematologist comprising six courses of dexamethasone, etoposide, ifosfamide, and carboplatin. The patient demonstrated long-term survival and was in remission at the time of writing, four years and five months after surgery.ConclusionsWe report a rare case of long-term survival of perforated ENKL of the small intestine achieved by surgery and adjuvant chemotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin. It is essential to consult with a hematologist to determine the most appropriate chemotherapy such as DeVIC if one encounters rare postoperative pathological findings of ENKL. To elucidate the pathophysiology of this disease and to prolong survival of affected patients, accumulation of cases of long-term survival and examination of associated characteristics is necessary.

Unmasking the truth Progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome PML IRIS in a 36 year old male with HIV

Progressive Multifocal Leukoencephalopathy – Immune Reconstitution Inflammatory Syndrome (PMLIRIS) is the subacute onset of neurological deficits that appeared or was exacerbated after initiation antiretroviral therapy (ART) for treatment of PML. It is due to severe neuroinflammation with re-establishment of immuncompetence. Approximately 25% of patients with HIV and PML develop IRIS. Clinical trials on the treatment of PML-IRIS is lacking with only limited evidence supporting the use of investigative therapies such as corticosteroids and Maraviroc. We report a case of a 36-year old Filipino male, known hypertensive and diagnosed with HIV, who presented with memory problems. He was eventually treated as a case of PML-IRIS on the 3rd week after initiation of ART. He was treated with a course of intravenous Dexamethasone, oral Mefloquine and intravenous immunoglobulin, and ART was continued. Clinical outcome in our patient shows an overall improvement of symptoms and no deterioration of neurologic deficits.

Unraveling Dexamethasone-Induced Neurobehavioral and Sleep Problems in Children With ALL: Which Determinants Are Important?

Dexamethasone, the preferred corticosteroid in most treatment protocols for pediatric acute lymphoblastic leukemia (ALL), can induce undesirable side effects. Neurobehavioral and sleep problems are frequently reported, but the interpatient variability is high. We therefore aimed to identify determinants for parent-reported dexamethasone-induced neurobehavioral and sleep problems in pediatric ALL. Our prospective study included patients with medium-risk ALL and their parents during maintenance treatment. Patients were assessed before and after one 5-day dexamethasone course. Primary end points were parent-reported dexamethasone-induced neurobehavioral and sleep problems, measured with the Strengths and Difficulties Questionnaire and Sleep Disturbance Scale for Children, respectively. Analyzed determinants included patient and parent demographics, disease and treatment characteristics, parenting stress (Parenting Stress Index and Distress Thermometer for Parents), dexamethasone pharmacokinetics, and genetic variation (candidate single-nucleotide polymorphisms rs41423247 and rs4918). Statistically significant determinants identified in univariable logistic regression analyses were incorporated in a multivariable model. We included 105 patients: median age was 5.4 years (range, 3.0-18.8) and 61% were boys. Clinically relevant dexamethasone-induced neurobehavioral and sleep problems were reported by parents in 70 (67%) and 61 (59%) patients, respectively. In our multivariable regression models, we identified parenting stress as a significant determinant for parent-reported neurobehavioral (odds ratio [OR], 1.16; 95% CI, 1.07 to 1.26) and sleep problems (OR, 1.06; 95% CI, 1.02 to 1.10). Furthermore, parents who experienced more stress before start of a dexamethasone course reported more sleep problems in their child (OR, 1.16; 95% CI, 1.02 to 1.32). We identified parenting stress, and not dexamethasone pharmacokinetics, genetic variation, patient/parent demographics, or disease/treatment characteristics, as a significant determinant for parent-reported dexamethasone-induced neurobehavioral and sleep problems. Parenting stress may be a modifiable target to reduce these problems.

Unmasking the Truth: Progressive Multifocal Leukoencephalopathy–Immune Reconstitution Inflammatory Syndrome (PML-IRIS) in a 36-year Old Male with HIV, A Case Report

Progressive Multifocal Leukoencephalopathy Immune Reconstitution Inflammatory Syndrome (PMLIRIS) is the subacute onset of neurological deficits that appeared or was exacerbated after initiation antiretroviral therapy (ART) for treatment of PML. It is due to severe neuroinflammation with reestablishment of immunocompetence. Approximately 25% of patients with HIV and PML develop IRIS. Clinical trials on the treatment of PML-IRIS is lacking with only limited evidence supporting the use of investigative therapies such as corticosteroids and Maraviroc. We report a case of a 36-year old Filipino male, known hypertensive and diagnosed with HIV, who presented with memory problems. He was eventually treated as a case of PML-IRIS on the 3rd week after initiation of ART. He was treated with a course of intravenous Dexamethasone, oral Mefloquine and intravenous immunoglobulin, and ART was continued. Clinical outcome in our patient shows an overall improvement of symptoms and no deterioration of neurologic deficits.

Delayed Onset ICANS Leading to Bilateral Cranial Neuropathies: Two Case Reports (P12-13.005)

<h3>Objective:</h3> To describe two cases of bilateral facial nerve neuropathy from late onset immune effector cell-associated neurotoxicity syndrome (ICANS) after chimeric antigen receptor T-cell (CAR-T) therapy for treatment of Multiple Myeloma. <h3>Background:</h3> ICANS is a complication of CAR-T therapy which typically occurs within the first week of treatment. Manifestations can include encephalopathy with confusion and behavioral changes, headache, agraphia, tremors, seizures, cerebral edema, or death. Isolated cranial neuropathies, particularly after this period, have not been reported. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> Two patients, a 69-year-old male (case 1) and a 67-year-old female (case 2), presented with facial nerve palsy 3 weeks (20 and 21 days respectively) after CAR-T therapy for multiple myeloma. Neither of the patients had developed symptoms of neurotoxicity immediately after CAR-T treatment. Case 1 experienced gradual onset of decreased taste, facial numbness, inability to smile or move his eyebrows, and drooling. Exam showed bilateral facial weakness in a lower motor neuron pattern, worse on the left as compared to the right. Case 2 experienced right-sided facial droop with inability to move her right eyebrow or symmetrically smile, right ear fullness, and right-sided drooling. Exam revealed right-sided facial weakness in a lower motor neuron pattern. MRI of the brain in both patients demonstrated bilateral contrast enhancement of the facial nerves. Cerebrospinal fluid analysis in case 1 showed mildly elevated protein (67 mg/dL), with negative infectious studies, and no evidence of malignancy. Case 2 did not have lumbar puncture, but respiratory viral and bacterial pathogen panel was negative. Both patients were treated with a short course of oral dexamethasone with complete resolution in case 1, and partial improvement of symptoms in case 2. <h3>Conclusions:</h3> Delayed ICANS should be considered in CAR-T patients presenting with isolated cranial neuropathies after ruling out infection and malignancy. Treatment with steroids can lead to recovery. <b>Disclosure:</b> Miss Beck has nothing to disclose. Dr. Hasan has nothing to disclose. Dr. Mehta has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Adamas Pharma. Dr. Mehta has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbott. Dr. Mehta has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CNS Ratings. Dr. Valencia Sanchez has nothing to disclose.

Hydrocortisone to reduce dexamethasone-induced neurobehavioral side-effects in children with acute lymphoblastic leukaemia—results of a double-blind, randomised controlled trial with cross-over design

BackgroundDexamethasone is a cornerstone of paediatric acute lymphoblastic leukaemia (ALL) treatment, although it can induce serious side-effects. Our previous study suggests that children who suffer most from neurobehavioural side-effects might benefit from physiological hydrocortisone in addition to dexamethasone treatment. This study aimed to validate this finding. MethodsOur phase three, double-blind, randomised controlled trial with cross-over design included ALL patients (3–18 years) during medium-risk maintenance therapy in a national tertiary hospital between 17th May 2018 and 5th August 2020. A baseline measurement before and after a 5-day dexamethasone course was performed, whereafter 52 patients with clinically relevant neurobehavioural problems were randomised to receive an intervention during four subsequent dexamethasone courses. The intervention consisted of two courses hydrocortisone (physiological dose 10 mg/m2/d in circadian rhythm), followed by two courses placebo, or vice versa. Neurobehavioural problems were assessed before and after each course using the parent-reported Strengths and Difficulties Questionnaire (SDQ) as primary end-point. Secondary end-points were sleep problems, health-related quality of life (HRQoL), hunger feeling, and parental stress, measured with questionnaires and actigraphy. A generalised mixed model was estimated to study the intervention effect. ResultsThe median age was 5.5 years (range 3.0–18.8) and 61.5% were boys. The SDQ filled in by 51 primary caregivers showed no difference between hydrocortisone and placebo in reducing dexamethasone-induced neurobehavioral problems (estimated effect -2.05 (95% confidence interval (CI) -6.00–1.90). Also, no benefit from hydrocortisone compared to placebo was found for reducing sleep problems, hunger, parental stress or improving HRQoL. ConclusionsHydrocortisone, when compared to placebo, had no additional effect in reducing clinically relevant dexamethasone-induced neurobehavioural problems. Therefore, hydrocortisone is not advised as standard of care for children with ALL who experience dexamethasone-induced neurobehavioural problems. Trial registrationNetherlands Trial Register NTR6695/NL6507 (https://trialsearch.who.int/) and EudraCT 2017–002738–22 (https://eudract.ema.europa.eu/).

Impact of dexamethasone on persistent symptoms of COVID-19: an observational study

Background: Dexamethasone has been shown to reduce mortality for patients hospitalised with acute coronavirus disease 2019 (COVID-19) pneumonia. However, a significant proportion of patients suffer persistent symptoms following COVID-19 and little is known about the longer-term impact of this intervention on symptom burden. Methods: Patients initially hospitalised with COVID-19 were prospectively recruited to an observational study (April-August 2020) with follow-up at 8 months (Dec 2020-April 2021) post-admission. A review of ongoing symptoms using a standardised systems-based proforma was performed alongside health-related quality of life assessment. In the UK, patients with COVID-19 (requiring oxygen) only received dexamethasone following the pre-print of the RECOVERY trial (June 2020), or as part of randomisation to that trial, allowing for a comparison between patients treated and not treated with dexamethasone. Results: Between April to August 2020, 198 patients were recruited to this observational study. 87 required oxygen and were followed up at 8-months, so were eligible for this analysis. Of these 39 received an inpatient course of dexamethasone (cases) and 48 did not (controls). The groups were well matched at baseline in terms of age, comorbidity and frailty score. Over two-thirds of patients reported at least 1 ongoing symptom at 8-month follow-up. Patients in the dexamethasone group reported fewer symptoms (n=73, 1.9 per patient) than the non-dexamethasone group (n=152, 3.2 per patient) (p = 0.01). Conclusions: In conclusion, in this case-control observational study, patients who received oral dexamethasone for hospitalised COVID-19 were less likely to experience persistent symptoms at 8-month follow-up. These are reassuring results for physicians administering dexamethasone to this patient group.

Risks and Preventions for Pregnant Women and Their Preterm Infants in a World with COVID-19: A Narrative Review.

(1) Background and Aim: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to increasing cases of coronavirus disease 2019 (COVID-19) around the world. COVID-19 infections have an important impact on pregnancy, preterm birth (PTB) and delivery. Although several complications have been reported in infected pregnant women, the effect of infection on PTB is controversial. The purpose of this study was to summarize the existing literature on the effects and complications of COVID-19 on the health of pregnant women and preterm babies and its impact on the incidence of PTB. We also discuss the effect of current COVID-19 vaccines during pregnancy. (2) Methods: We carried out a systematic search of MEDLINE, Embase, and PubMed for studies on preterm births associated with COVID-19. (3) Results and Conclusions: We discovered contradictory results regarding the prevalence of PTB during the pandemic compared to earlier years. While most studies indicated an increase in PTBs with COVID-19, some indicated a decline in the preterm delivery rate during this time. During pregnancy, COVID-19 infection can increase the incidence of cesarean section, stillbirth, ICU admission, preeclampsia/eclampsia, and mortality rates. In the treatment of pregnant women with severe COVID-19, methylprednisolone was favored over prednisolone, and a brief course of dexamethasone is advised for pregnant women with anticipated PTB to accelerate the development of the fetal lung. Generally, vaccination for COVID-19 in pregnant and lactating women stimulates anti-SARS-CoV2 immune responses, and it does not result in any noteworthy negative reactions or outcomes for the mother or baby.

The role of chondrocyte-to-osteoblast trans-differentiation in fetal bone dysplasia of mice caused by prenatal exposure to dexamethasone.

Maternal exposure to dexamethasone can cause developmental toxicity of long bones in offspring. However, the effect of dexamethasone on the trans-differentiation of growth plate chondrocytes into osteoblasts and its role in bone dysplasia of fetuses caused by prenatal dexamethasone exposure (PDE) remains unclear. In this study, pregnant mice were treated with different doses, stages, and courses of dexamethasone according to clinical practice to reveal the phenomenon. Further, growth plate chondrocytes were treated with dexamethasone in vitro to clarify the phenomenon and mechanism. The results showed that PDE caused dysplasia of fetal long bones in female and male mice, accompanied by the delayed formation of the primary ossification center and the widening hypertrophic zone of growth plate cartilage. Meanwhile, PDE increased the number of hypertrophic chondrocytes at growth plate cartilage and decreased the number of osteoblasts at the primary ossification center. Moreover, PDE significantly decreased the expression of osteogenic transcription factor Runx2 but increased the expression of hypertrophic chondrocytes marker Col10. These above phenomena were more significant in the high dose, early stage, and double courses of dexamethasone exposure groups, and the male fetal mice showed more obvious than the female fetal mice. In vitro, dexamethasone significantly inhibited the trans-differentiation of growth plate chondrocytes into osteoblasts, accompanied by a decrease in Runx2 expression and an increase in Col10 expression. In conclusion, this study revealed the phenomenon and mechanism of fetal bone dysplasia caused by PDE from the new perspective of trans-differentiation disorder of growth plate chondrocytes to osteoblasts.

Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis (RECORDS): study protocol for a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial

IntroductionCorticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients’ response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes associated...

An interval of clinically silent gastrointestinal bleed in dysautonomic spinal cord injury: a case report

BackgroundGastrointestinal bleed (GIB) has high incidence in traumatic spinal cord injured (tSCI) patients and can frequently be life-threatening, especially early post-injury. Several risk factors often compound bleeding risk, some are unique to this patient population. Normally, clinical suspicion for GIB arises from symptoms like coffee-ground emesis, hematemesis, melena or even hematochezia. A hemoglobin drop may be a late sign. Due to tSCI, however, patients often experience neurogenic bowels and dysautonomia, which may delay symptom presentation and complicate timely diagnosis of GIB. We report a case of an almost clinically silent GI bleed in the context of acute cervical tSCI.Case presentationA 21-year-old female presented with cervical cord transection at C-7 in the setting of motor vehicle rollover, for which surgical decompression was performed. During the acute injury phase, she also received a 10-day course of dexamethasone for symptomatic COVID-19 pneumonia. Two weeks after injury, she underwent percutaneous endoscopic gastrostomy (PEG) placement which demonstrated normal gastric and duodenal anatomy. One week later, a large spike (10x) in blood urea nitrogen: creatinine (BUN: Cr) ratio raised concern for GIB, but hemoglobin remained stable, and stool color remained unchanged. The following day, a gastroenterology consult was requested under increased suspicion of GIB from a sudden 3.5 g/dL hemoglobin drop. The patient received blood transfusion and pantoprazole. An upper endoscopy was performed, revealing three small duodenal ulcers. Melanotic stool ensued afterwards.ConclusionsDue to dysautonomia, clinical presentation of GIB can be significantly delayed in the tSCI patient population, leaving them vulnerable to succumb to illness. This case illustrates the possibility of an interval in which the patient was bleeding, with the sole indicator being an elevated BUN. Our case calls for closer monitoring of and vigilance for tSCI patients, and possibly employment of different strategies to reduce the incidence and enhance early detection of GIB in tSCI patients to subsequently decrease the morbidity and mortality associated with it.

Benefits of dexamethasone on early outcomes in patients with acute myeloid leukemia with hyperleukocytosis: a propensity score matched analysis.

Hyperleukocytosis is associated with a significant early mortality rate in patients with acute myeloid leukemia (AML). To date, no controlled trial has ever evaluated a strategy to reduce this risk, and the initial management of these patients remains heterogeneous worldwide. The aim of the present study was to evaluate the influence of a short course of intravenous dexamethasone on the early outcomes of patients with hyperleukocytic AML with white blood cell (WBC) count above 50 × 109/L. Clinical and biological data of all consecutive patients (1997-2017) eligible for intensive chemotherapy from a single center were retrospectively collected. A total of 251 patients with a median age of 51years and a median WBC count of 120 × 109/L were included, 95 of whom received dexamethasone. Patients treated with dexamethasone had higher WBC count and a more severe disease compared with those who did not, and they presented more often with leukostasis and hypoxemia, resulting in a more frequent need for life-sustaining therapies (p < 0.001). To account for these imbalances, patients were compared after adjusting for a propensity score, which included all variables with a prognostic influence in the overall cohort. In the matched cohort, dexamethasone was associated with lower early death (OR = 0.34, p = 0.0026) and induction failure rate (OR = 0.44, p = 0.02) and better overall survival (HR = 0.60, p = 0.011), with no impact on relapse risk (cHR = 0.73, p = 0.39). The overall survival benefit was confirmed among all tested subgroups. This study suggests that dexamethasone administration is safe and associated with a lower risk of induction mortality in patients with hyperleukocytic AML and deserves prospective evaluation.

An unusual early and persistent symptomatic presentation of peri-lead edema following deep brain stimulation: Case report and literature review

BackgroundPeri-lead edema (PLE) following deep brain stimulation surgery is apparently a common, self-limiting condition. PLE generally occurs within days to weeks, rarely occurring before postoperative day one. Majority of patients are asymptomatic, although a wide range of sings/symptoms may be present. Case descriptionA 62-year-old female patient with Parkinson’s Disease underwent DBS of the subthalamic nucleus in November 2018. Asymptomatic, the patient presented bilateral PLE in the immediate post-operative CT. After two weeks, she developed a frontal lobe dysfunction and persistence of PLE in MRI. She underwent a three-week course of dexamethasone, with mild improvement. However, she subsequently fell at home in January 2019, sustaining an injury to the scalp over the connection site surgical incision. Due to persisting PLE, this was managed with a new course of Dexamethasone, and she was followed-up with CT scans. Two months later (March 2019) the patient presented with urinary tract infection and a lateral scalp erosion over the lead’s connection site. Debridement and primary closure of the skin were performed, followed by a four-week vancomycin course. A MRI at the stage showed marked improvement of the edema. The most recent MRI (May 2019) and CT scan (July 2019) showed resolution of the edema. ConclusionsWe reported an atypical case of ultra early and persistent PLE presentation following DBS surgery, which improved with courses of steroids. It is unknown whether steroids have a role in the management of PLE.

Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19.

Prospective observational cohort. ICUs in three University of Washington affiliated hospitals between July 2020 and April 2021. Patients admitted to an ICU with COVID-19 who completed a course of dexamethasone. We identified 65 adult patients with severe COVID-19 who completed a 10-day course of dexamethasone, of whom 60 had plasma samples collected within 3 days of dexamethasone completion. We measured IL-6 with a clinical-grade electrochemiluminescent assay and a larger panel of inflammatory biomarkers (IL-8, Monocyte Chemoattractant Protein-1, Monocyte Inflammatory Protein-1 alpha, interferon gamma, C-X-C Motif Chemokine Ligand 10, WBC, bicarbonate) with a research immunoassay. We defined clinical decline by the occurrence of incident severe kidney injury, incident or escalating shock or fever, worsening hypoxemia, or death within 5 days of completion of dexamethasone. We estimated risk for clinical decline by standardized log2 transformed biomarker concentration using multivariable logistic regression. Clinical decline post-dexamethasone was common, occurring in 49% of patients (n = 32). Among all biomarkers, IL-6 levels were most strongly associated with clinical decline. After adjustment for age, sex, and study site, the odds of post-dexamethasone clinical decline were 7.33 times higher per one sd increase in log2 transformed IL-6 concentrations (adjusted odds ratio, 7.33; CI, 2.62-20.47; p < 0.001). The discriminatory power of IL-6 for clinical decline was high (cross-validated mean area under the receiver operating characteristic curve, 0.90; 95% CI, 0.79-0.95). Clinical decline after completion of dexamethasone for severe COVID-19 is common. IL-6 concentrations obtained prior to completion of dexamethasone may have utility in identifying those at highest risk for subsequent worsening. If validated, future work might test whether plasma IL-6 could be used as a tool for a personalized approach to duration of dexamethasone treatment in severe COVID-19.

Long course of low-dose dexamethasone following or after bleomycin administration ameliorates pulmonary fibrosis.

DXM is widely used as an antifibrotic agent due to its protection of the lungs against fibrosis by inhibiting the production of inflammatory mediators. Many studies clearly indicated that the time point at which DXM treatment started, the dose and the duration of intervention are critical for exerting its antifibrotic effect. Exploring the role of DXM in the occurrence and development of PF at different stages is the fundamental purpose of this article. Lung fibrosis was persuaded in Sprague-Dawley rats by a single intratracheal BLM (5mg/kg) injection. This experiment was divided into two animal experiments and treated with DXM following or after bleomycin administration respectively. The biochemical, histopathological and molecular alterations were studied in the lung tissues. A long course of low-dose DXM had the ability to ameliorate PF induced by BLM via decreasing inflammation and improving oxidative stress through modulation of TGF-β/Smad, PI3K/Akt/mTOR and NF-κB signaling pathway. Long course of low-dose DXM intake following or after bleomycin administration both had therapeutic effects on pulmonary fibrosis.

S41 Unusual Case of Tongue Deviation

Case: Background: Anti-tumor necrosis factor-α (TNFα) therapy is the mainstay of treatment for inflammatory bowel disease such as Crohn’s Disease (CD) and ulcerative colitis (UC). Despite its widespread use, anti-TNFα leads to significantly altered inflammatory response and increased risk of severe skin and soft tissue infections. Here, we highlight an uncommon presentation of severe soft tissue infection in a patient with ileal CD maintained on anti-TNFα therapy. Case Presentation: A 50-year-old female with a 25-year history of Crohn's ileitis maintained on certolizumab for 3 years presented to the emergency department (ED) with an expanding left, lateral neck mass resulting in decreased cervical range of motion. This was accompanied by a left-sided tongue deviation. She first presented to our ED 8 weeks earlier with severe throbbing headaches without focal neurologic symptoms. A head MRI only showed non-specific T2/FLAIR hyperintensities. Her vital signs and labs were normal, and these headaches were presumed to be complex migraines. Three weeks after her first presentation, she came back to the ED with worsening headaches, neck pain and a new left-sided tongue deviation. Again, her vital signs and laboratory evaluation were normal apart from an ESR of 68 mm/hr (nl: 0-30 mm/hr) and CRP of 10.34 mg/dL (nl<0.5 mg/dL). Her repeat imaging studies did not show any evidence of stroke; however, opacification of the paranasal sinuses and left mastoid air cells were observed. Nonetheless, given her lack of systemic inflammatory symptoms, she was discharged home with close outpatient otolaryngology (ENT) referral. As an outpatient, she was diagnosed with bacterial sinusitis which was treated with a 15-day course of cefdinir and dexamethasone. Her symptoms initially improved; however, she eventually experienced dysphagia with pus drainage from her sinuses. Another antibiotic and steroid course was prescribed. Despite this, approximately 8 weeks after her initial presentation, she developed a rapidly expanding neck mass which prompted her return to the ED. Physical examination revealed a tender neck mass limiting her cervical range of motion and a more pronounced tongue deviation. She was afebrile, non-tachycardiac, and normotensive. Laboratory testing again revealed elevated inflammatory markers (ESR 83 mm/hr, CRP 8.59 mg/dL) but otherwise her WBC was normal (8310 cells/ µL, nl: 10400 cells/µL) with no evidence of sepsis-related end-organ dysfunction (Cr 0.89 mg/dL, AST 20, ALT 55 mg/dL, T-bili 0.3 mg/dL, platelets 348000 platelets/µL). Neck imaging showed multifocal ring-enhancing collections within the left paravertebral soft tissue with left hypoglossal nerve involvement. Intravenous vancomycin, cefepime, and metronidazole were started. Surgical debridement of the left posterior paraspinal abscess was performed. Intraoperative cultures were positive for Streptococcus anginosus. She completed a 6-week course of ceftriaxone but follow up imaging 2 weeks later showed recurrence of her neck abscesses. This again required surgical debridement. Her infections finally cleared with 24 weeks of piperacillin/tazobactam. Her certolizumab remains permanently discontinued. Conclusions: Hallmark symptoms of severe infection may not be present in patients on anti-TNF therapy. A high index of suspicion for an underlying infectious etiology must be maintained when treating this population.

Unresolved issues on the antenatal use of corticosteroids for fetal lung maturation

Antenatal corticosteroids (ACS) for fetal lung maturation is celebrating the 50th anniversary. The most recent Cochrane review concluded that there is robust evidence that a single course of ACS reduces the risk of perinatal death and respiratory distress syndrome. Some aspects of ACS remain unresolved, including variations in the steroids regimen, effectiveness in certain groups, long-term effects, optimal timing of ACS administration in elective cases. it is well established that a single course of betamethasone or dexamethasone is beneficial in cases of anticipated preterm birth and delivery eventually occurs between two and seven days from administration. The main focus for future research should be on limiting the unnecessary exposure in low-risk pregnancies and investigating the effect in specific groups, periviable and late preterm fetuses.

A case-control study on the effects of incomplete, one, and more than one dexamethasone course on acute respiratory problems in preterm neonates born between 280 and 366 weeks of gestation

ObjectiveTo compare the effects of an incomplete course and more than 1 course of dexamethasone, relative to a control of a single complete course, on foetal respiratory problems and other adverse outcomes of preterm birth.MethodsThis was a retrospective chart review of 1800 women with preterm delivery. Data were collected on newborns whose mothers administered 1 full course of dexamethasone (916/1800; 50.9%), a partial course (716/1800; 39.8%) and more than 1 course (168/1800; 9.3%). Demographic data and adverse maternal and neonatal outcomes were recorded.ResultsPreterm singleton newborns whose mothers received several steroid hormone courses were significantly more likely to have adverse outcomes than newborns of mothers given 1 course. The negative outcomes were the need for positive pressure ventilation ([aOR] 1.831; 95% CI, (1.185,2.829); P = 0.019), ventilator support ([aOR] 1.843; 95% CI, (1.187,2.861); P = 0.011), and phototherapy ([aOR] 1.997; 95% CI, (1.378,2.895); P < 0.001), transient tachypnoea of the newborn ([aOR] 1.801; 95% CI, (1.261,2.571); P = 0.002), intraventricular haemorrhage ([aOR] 2.215; 95% CI, (1.159, 4.233); P = 0.027), sepsis ([aOR] 1.737; 95% CI, (1.086, 2.777); P = 0.007), and admission to neonatal intensive care ([aOR] 1.822; 95% CI, (1.275,2.604); P = 0.001). In the group of very preterm infants, newborns of mothers administered an incomplete course had developed respiratory distress syndrome (RDS) ([aOR] 3.177; 95% CI, (1.485, 6.795); P = 0.006) and used ventilatory support ([aOR] 3.565; 95% CI, (1.912, 6.650); P < 0.001) more than those of mothers receiving a single course.ConclusionsPreterm singleton newborns whose mothers were given multiple courses of dexamethasone had an increased incidence of RDS and other adverse outcomes than those of mothers receiving a full course. However, very preterm newborns whose mothers were administered 1 full dexamethasone course had a significantly lower incidence of RDS than those whose mothers were given partial courses.

Hydrocortisone or Placebo to Reduce Dexamethasone-Induced Neurobehavioral Side Effects: Results of a Phase 3 National, Double-Blind, Placebo-Controlled Randomized Trial with Crossover Design

Background The introduction of dexamethasone for the treatment of pediatric acute lymphoblastic leukemia (ALL) significantly contributed to the current overall survival rate of more than 90% in high-income countries. The downside however, is that dexamethasone can induce serious side effects, of which neurobehavioral side effects are experienced as detrimental with respect to health-related quality of life (HRQoL) by both patients and parents. Our previous study suggests that children who suffer most from neurobehavioral side effects might benefit from physiological hydrocortisone addition to dexamethasone treatment. We aimed to validate this finding in a prospective large cohort of pediatric ALL patients. Methods Our phase 3, double-blind, randomized controlled trial with crossover design included ALL patients (3-18 years) during medium risk maintenance therapy in a national tertiary hospital between May 17, 2018 and August 5, 2020. A baseline measurement before and after one five-day dexamethasone course was performed to identify patients with clinically relevant dexamethasone-induced neurobehavioral problems, defined as a rise of ≥5 points on the Strengths and Difficulties Questionnaire (SDQ) Total Difficulties score. These patients were subsequently randomized to receive an intervention during the following four five-day dexamethasone courses. The intervention consisted of two courses hydrocortisone (physiological dose of 10mg/m2/day in a circadian rhythm), followed by two courses placebo, or vice versa. Neurobehavioral problems were assessed before and after each course using the parent-reported SDQ as primary endpoint. Secondary endpoints were sleep problems, HRQoL, hunger feeling, and parental stress, measured with separate questionnaires and actigraphy. A generalized mixed model was estimated to study the intervention effect. Findings Of 79 included patients, 52 (66%) experienced clinically relevant dexamethasone-induced neurobehavioral problems. Both hydrocortisone and placebo significantly and relevantly decreased dexamethasone-induced neurobehavioral problems measured with the SDQ (estimated effect hydrocortisone: -8.19 (95%-confidence interval (CI) -12.35 to -4.04), estimated effect placebo: -6.75 (95%-CI -10.95 to -2.56) (table 1 and figure 1). This indicates that, when adding hydrocortisone or placebo to dexamethasone treatment, the SDQ Total Difficulties score is estimated to be 8.19 or 6.75 points lower than without the addition of hydrocortisone or placebo. Since one SD of SDQ norm values is between 4 and 6 points, the decrease on the SDQ after hydrocortisone or placebo addition is more than 1 SD, and therefore clinically significant. The strength of the effect was similar in both interventions. There was no benefit from hydrocortisone or placebo in reducing sleep problems, hunger, parental stress or improving HRQoL. Interpretation Clinically relevant dexamethasone-induced neurobehavioral problems decreased equally and significantly after both hydrocortisone and placebo addition. Using the placebo effect in clinical practice could be a powerful and innovative way to diminish neurobehavioral problems in children who experience clinically relevant dexamethasone-induced side effects. Moreover, the high proportion of patients who experience clinically relevant dexamethasone-induced neurobehavioral problems might be caused by a nocebo effect of dexamethasone. By offering both interventions (hydrocortisone and open-label placebo) in clinical practice and by diminishing the nocebo effect of dexamethasone, we hope to improve dexamethasone-induced side effects in those patients who suffer most. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effects of antenatal corticosteroids on neonatal blood glucose fluctuation in late-preterm infants.

To evaluate the effects of antenatal corticosteroids (ACS) on blood glucose fluctuations in late-preterm neonates. A retrospective study was performed on 236 neonates with gestational age of 34+0 to 36+6 weeks who were admitted to the neonatology department of a tertiary general hospital in China's Zhejiang Province between April 2020 and February 2022. The neonates were divided into three groups: complete course, partial course, and control. Primary outcome was the neonatal blood glucose levels within the first 48 h of life. 134 (56.8%) newborns were exposed to a complete course of ACS, 56 (23.7%) had a to a partial course of ACS, and 46 (19.5%) had no exposure to ACS. The patients in the complete course group had the highest proportion of neonatal hypoglycemia (16.4% vs. 3.6% and 6.5%).The patients exposed to a complete course of dexamethasone had significantly lower blood glucose levels within 12 h of birth than the control group, although no significant differences were observed after 24 h. Differences in blood glucose levels were more significant among male infants, although blood glucose curves of the male and female infants remained close to the overall trend. Blood glucose levels in late-preterm neonates may decrease after ACS administration, especially after exposure to a complete course. The effects are more pronounced in the first 12 h of life, with males being more severely affected; however, the effects on blood glucose levels were not significant 24 h after birth. This can provide a reference for future clinical studies.