Biologic treatment for severe chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is often severe, debilitating and difficult to treat. Biologics that target key inflammatory pathways have the potential to treat this disease; this study aimed to evaluate their effectiveness. METHODOLOGY: Systematic review and meta-analysis of randomised controlled trials of biologics in chronic rhinosinusitis with nasal polyps. Primary outcomes were extent of disease, objective disease severity and disease-specific quality of life, with outcomes measured at different end-of-treatment timepoints in different studies (range 16-52 weeks). RESULTS: Eleven trials were identified with 2035 participants. Ten studies reported change in polyp size, estimating a reduction of -1.25 in the treatment group. Six studies reported reduction in Lund-Mackay score where the pooled mean difference was -4.90. Five studies included peak nasal inspiratory flow with a pooled mean difference of 33.54, indicating improved nasal airflow. Seven studies reported change in olfactory score with an overall pooled effect of 6.56 suggesting improved olfaction. The SNOT-22 score in nine studies gave an overall pooled effect of -14.53, indicating improved quality of life. CONCLUSIONS: Biologics can be effective in treating nasal polyps, with reduction in polyp size and extent of disease, and improved sense of smell and quality of life. There is significant heterogeneity in the outcomes for individual biologics, highlighting the need for further studies.

Liposomal Bupivacaine Plus Bupivacaine Versus Ropivacaine Plus Dexamethasone Brachial Plexus Blockade for Arthroscopic Rotator Cuff Repair: An Unblinded Randomized Controlled Trial.

Brachial plexus blockade is utilized for pain control during arthroscopic rotator cuff repair. The purpose of the present study was to evaluate brachial plexus blockade with liposomal bupivacaine plus bupivacaine (LB+B) as compared with ropivacaine plus dexamethasone (R+D) for arthroscopic rotator cuff repair. Our hypothesis was that the use of LB+B would result in lower pain scores and opioid consumption as compared with R+D. Methods: We performed a randomized controlled trial of 45 patients receiving ultrasound-guided brachial plexus blockade with LB+B and 44 patients receiving R+D prior to arthroscopic rotator cuff repair. The "worst pain" score in a 24-hour period, oral morphine equivalent dose (OMED), and overall benefit of analgesia score (OBAS) were recorded for 8 days following surgery. Results: Patient-reported "worst pain" was significantly lower in the LB+B group as compared with the R+D group on postoperative day 0 through day 5. OMED was significantly less for all 8 days studied, with an average cumulative 8-day OMED of 48.5 milligram equivalents in the LB+B group as compared with 190.1 milligram equivalents in the R+D group (p < 0.001). The OBAS score was significantly lower in the LB+B group as compared with R+D group on all postoperative days. The use of LB+B for brachial plexus blockade resulted in a 4% complication rate in a population of patients predominantly with American Society of Anesthesiologists (ASA) scores of 1 and 2. Conclusions: The use of LB+B for brachial plexus blockade during arthroscopic rotator cuff repair was associated with a significant and sustained decrease in the "worst pain" score, opioid consumption, and OBAS compared with R+D. LB+B for brachial plexus blockade also exhibited a strong safety profile. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Early surgery determines prognosis in patients with infective endocarditis: outcome in patients managed by an Endocarditis Team-a prospective cohort study.

Background: Infective endocarditis (IE) in South Africa is associated with significant morbidity and mortality, despite occurring in younger patients with fewer co-morbidities. Possible contributors include the high rates of blood culture negative endocarditis, high rates of mechanical valve replacement and the lack of inter-disciplinary coordination during management. Methods: The Tygerberg Endocarditis Cohort (TEC) study prospectively enrolled patients with IE between November 2019 and April 2021. All patients were managed by an Endocarditis Team with a set protocol for organism detection and a strategy of early surgery limiting the use of prosthetic material. Results: Seventy-two consecutive patients with IE were included, with a causative organism identified in 86.1% of patients. The majority of patients had a guideline indication for surgery (n=58; 80.6%). The in-hospital mortality rate was 18%, with a 6-month mortality rate of 25.7%. Surgery was performed in 42 patients (58.3%), with prosthetic valve (PVE) replacement in 32 (76.2%), conventional repair surgery in 8 (19.1%) and mitral valve reconstruction in 2 (4.8%) of patients. Patients who underwent surgery had a significantly lower in-hospital (4.8% vs. 56.3%; P<0.01) and 6-month (4.9% vs. 75.0%; P<0.01) mortality rate as compared with patients with an indication for surgery who did not undergo surgery. Conclusions: We have observed a reduction in the 6-month mortality rate in patients with IE following the establishment of an Endocarditis Team, adhering to a set protocol for organism detection and favouring early repair or reconstruction surgery. Patients who underwent surgery had a significantly lower mortality rate than patients with an indication for surgery who did not undergo surgery. Preventable residual mortality was driven by surgical delay.

Clinical care pathways for ambulatory total shoulder arthroplasty.

PURPOSE OF REVIEW: Total shoulder arthroplasty (TSA) is growing in popularity and is increasingly done on an ambulatory basis. This review examines recent developments in anesthesia and analgesia for ambulatory shoulder surgery. Pathway components are discussed and a sample pathway is described. RECENT FINDINGS: Adoption of pathways for shoulder surgery improves patient experience by reducing pain, opioid use, and side effects while improving patient satisfaction. Long-acting nerve blockade using adjuvants like dexamethasone provide long-lasting analgesia without rebound pain. Peripheral nerve blockade provides better analgesia than peri-articular injection of local anesthetic. There are multiple approaches to nerve blockade for shoulder surgery to consider, including interscalene, superior trunk, supraclavicular, and anterior suprascapular nerve blocks. Multimodal analgesia should include acetaminophen and nonsteroidal anti-inflammatory drugs, but routine gabapentinoids should not be used. SUMMARY: Anesthesiologists should lead the way to create and implement pathways for ambulatory total shoulder arthroplasty, incorporating appropriate patient selection, patient education, long-lasting nerve blockade, and multimodal analgesia.

Tuberculous bronchial stenosis: Diagnosis and role of interventional bronchoscopy.

The reported prevalence of tuberculous bronchial stenosis in children is unknown and rarely reported in English-speaking literature. In adult patients with pulmonary tuberculosis, it varies from 40% in an autopsied series in the preantibiotic era to 10% in patients who have undergone routine bronchofibroscopy in modern times. We describe our experience of four cases of confirmed bronchial stenosis due to MTB collected between January 2000 and June 2021 in this case series descriptive study. The diagnosis of bronchial stenosis due to TB was made on flexible bronchoscopy. A TB diagnosis was made if MTB was cultured from respiratory secretions, when Ziehl-Neelsen smear or GeneXpert MTB/RIF test was positive, or if a chest radiograph revealed radiographic features typical of MTB. Bronchial stenosis due to TB is rare even if airway compression is frequently seen. Although an early diagnosis of bronchial stenosis due to TB is difficult on chest X-rays, all children in this series demonstrated parenchymal changes distal to the stenosis ranging from hyperinflation and lobar collaps to bronchiectasis. If bronchial stenosis resulting from TB disease is diagnosed early, balloon dilatation as described in this report, may be an effective and safe intervention, preventing long-term complications such as irreversible lung destruction, that may require pneumonectomy.

Effect of Duloxetine on Opioid Use and Pain After Total Knee Arthroplasty: A Triple-Blinded Randomized Controlled Trial.

BACKGROUND: Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total knee arthroplasty (TKA). Previous studies had one primary outcome, did not consistently use multimodal analgesia, and used patient-controlled analgesia devices, potentially delaying discharge. We investigated whether duloxetine would reduce opioid consumption or pain with ambulation. METHODS: A total of 160 patients received 60 mg duloxetine or placebo daily, starting from the day of surgery and continuing 14 days postoperatively. Patients received neuraxial anesthesia, peripheral nerve blocks, acetaminophen, nonsteroidal anti-inflammatory drugs, and oral opioids as needed. The dual primary outcomes were Numeric Rating Scale (NRS) scores with movement on postoperative days 1, 2, and 14, and cumulative opioid consumption surgery through postoperative day 14. RESULTS: Duloxetine was noninferior to placebo for both primary outcomes and was superior to placebo for opioid consumption. Opioid consumption (mean ± SD) was 288 ± 226 mg OME [94, 385] vs 432 ± 374 [210, 540] (duloxetine vs placebo) P = .0039. Pain scores on POD14 were 4.2 ± 2.0 vs 4.8 ± 2.2 (duloxetine vs placebo) P = .018. Median satisfaction with pain management was 10 (8, 10) and 8 (7, 10) (duloxetine vs placebo) P = .046. Duloxetine reduced interference by pain with walking, normal work, and sleep. CONCLUSION: The 29% reduction in opioid use corresponds to 17 fewer pills of oxycodone, 5 mg, and was achieved without increasing pain scores. Considering the ongoing opioid epidemic, duloxetine can be used to reduce opioid usage after knee arthroplasty in selected patients that can be appropriately monitored for potential side effects of the medication.

Pulmonary Echinococcus in children: A descriptive study in a LMIC.

BACKGROUND: Echinococcus granulosus is a major public health problem in lower middle-income countries (LMIC). Children are commonly diagnosed with cysts in the lungs and/or the liver. OBJECTIVES: The purpose of this study was to describe a pediatric cohort diagnosed with pulmonary Cystic Echinococcus (CE) and treated with a combination of medical and surgical therapy. METHODS: This was a retrospective study performed between July 2017 and December 2020 at Tygerberg Hospital, South Africa. Clinical, laboratory, radiological, medical, and surgery-related outcomes were reviewed. RESULTS: The cohort consisted of 35 children, 17 (49%) were male, with a mean age of 9 ± 5.4 years. The most frequently encountered presenting symptom was cough (93%) followed by fever (70%). Isolated pulmonary CE accounted for the majority of cases (74%) with left lower lobe predominance. A significant proportion of the cohort exhibited chest computed tomography (CT) characteristics consistent with complicated pulmonary CE. Eighteen (58%) children had a positive indirect hemagglutination assay (IHA) test result. All children received medical treatment whilst 30 (86%) of children required surgery. Children with complicated pulmonary CE stayed a mean of 12.5 ± 6.6 days, while those with simple cysts stayed 6.8 ± 1.5 days. CONCLUSION: Isolated pulmonary CE is common in children, whereas extrapulmonary cysts are uncommon. Pulmonary CE is diagnosed using chest X-ray and, CT imaging. IHA serology has limited diagnostic utility for pulmonary CE. Combined surgery and chemotherapy remains the gold standard for treating pulmonary CE.

Inter- and intra-observer agreement for grading radiographs of thoracolumbar spinous processes in healthy horses during a pre-purchase examination.

BACKGROUND: There is wide variability in radiographic grading systems in thoracolumbar spinous processes in horses. The aim of this study was to determine the agreement of grading different parameters, and combinations of those, in radiographs of the spinous processes of the equine thoracolumbar spine in the scope of a pre-purchase examination. We hypothesized that agreement is variable and interpretation of these radiographs is difficult. METHODS: Radiographs of the thoracolumbar spine of healthy horses (N = 100) were assessed by three observers. Spinous processes were separately graded for interspinous space width, modelling, radiopacities, radiolucencies and isolated opacities dorsally. Inter- and intra-observer agreement was assessed for individual and combinations of parameters. RESULTS: Agreement (inter- and intra-observer) was good for the following parameters: interspinous space width, isolated opacities dorsally, beak-shaped formations craniodorsally and modelling cranioventrally. The agreement increased slightly for a sum of specific parameters such as radiopacities, modelling, dorsal abnormalities and related abnormalities involving increased opacity, modelling and osseous cyst-like lesions. Agreement for the total radiographic abnormalities per back was moderate. CONCLUSIONS: Grading of thoracolumbar radiographs in horses without back pain showed good inter- and intra-observer agreement for specific parameters and these should be used in future grading of spinous processes. Limitations should be considered in pre-purchase examinations.

EPOS 4 Patients.

EPOS2020 is the 4th and most recent version of the European Position Paper on Rhinosinusitis and Nasal Polyps which was first published in 2005. It aims to provide the most up to date scientifically robust information on the topic published in the literature which has been critically analysed by an international group of clinicians drawn from all disciplines dealing with these problems together with patients. The guidelines offer evidence-based recommendations and care pathways for acute and chronic rhinosinusitis in both adults and children. Management of these diseases from the patients' perspective is an important part of EPOS2020. Not only is this included in the main document but, for the first time, we have produced a separate supplement dedicated to and in collaboration with patients, EPOS4Patients, which aims to provide information in an accessible format, to answer frequently asked questions about these diseases and their treatment options as well as including useful patient resources and websites. It has never been more important for patients to be actively involved in their care. Being well informed helps you to make the best decisions together with your doctor.

Midazolam-Induced Hiccups Reversed by Flumazenil: A Case Report.

Hiccups are a common phenomenon experienced by many people and are usually short-lived with spontaneous resolution of symptoms. Certain anesthetic medications have been associated with the development of hiccups, though the underlying pathophysiology and reflex arcs remain poorly understood. We describe a patient who developed hiccups lasting 9 days following an orthopedic surgery and again developed hiccups during a subsequent surgery after only having received midazolam; flumazenil administration led to sustained cessation of his hiccup symptoms immediately.

A Comprehensive Enhanced Recovery Pathway for Rotator Cuff Surgery Reduces Pain, Opioid Use, and Side Effects.

BACKGROUND: Patients often have moderate to severe pain after rotator cuff surgery, despite receiving analgesics and nerve blocks. There are many suggested ways to improve pain after rotator cuff surgery, but the effects of adopting a pathway that includes formal patient education, a long-acting nerve block, and extensive multimodal analgesia are unclear. QUESTIONS/PURPOSES: (1) Does adoption of a clinical pathway incorporating patient education, a long-acting nerve block, and preemptive multimodal analgesia reduce the worst pain during the first 48 hours after surgery compared with current standard institutional practices? (2) Does adoption of the pathway reduce opioid use? (3) Does adoption of the pathway reduce side effects and improve patient-oriented outcomes? METHODS: From September 2018 to January 2020, 281 patients scheduled for arthroscopic ambulatory rotator cuff surgery were identified for this paired sequential prospective cohort study. Among patients in the control group, 177 were identified, 33% (58) were not eligible, for 11% (20) staff was not available, 56% (99) were approached, 16% (29) declined, 40% (70) enrolled, and 40% (70) were analyzed (2% [4] lost to follow-up for secondary outcomes after postoperative day 2). For patients in the pathway cohort, 104 were identified, 17% (18) were not eligible, for 11% (11) staff was not available, 72% (75) were approached, 5% (5) declined, 67% (70) enrolled, and 67% (70) were analyzed (3% [3] lost to follow-up for secondary outcomes after postoperative day 2). No patients were lost to follow-up for primary outcome; for secondary outcomes, four were lost in the control group and three in the pathway group after postoperative day 2 (p = 0.70). The initial 70 patients enrolled received routine care (control group), and in a subsequent cohort, 70 patients received care guided by a pathway (pathway group). Of the 205 eligible patients, 68% (140) were included in the analysis. This was not a study comparing two tightly defined protocols but rather a study to determine whether adoption of a pathway would alter patient outcomes. For this reason, we used a pragmatic (real-world) study design that did not specify how control patients would be treated, and it did not require that all pathway patients receive all components of the pathway. We developed the pathway in coordination with a group of surgeons and anesthesiologists who agreed to apply the pathway as much as was viewed practical for each individual patient. Patients in both groups received a brachial plexus nerve block with sedation. Major differences between the pathway and control groups were: detailed patient education regarding reasonable pain expectations with a goal of reducing opioid use (no formal educational presentation was given to the control), a long-acting nerve block using bupivacaine with dexamethasone (control patients often received shorter-acting local anesthetic without perineural dexamethasone), and preemptive multimodal analgesia including intraoperative ketamine, postoperative acetaminophen, NSAIDs, and gabapentin at bedtime, with opioids as needed (control patients received postoperative opioids but most did not get postoperative NSAIDS and no controls received gabapentin or separate prescriptions for acetaminophen). The primary outcome was the numerical rating scale (NRS) worst pain with movement 0 to 48 hours after block placement. The NRS pain score ranges from 0 (no pain) to 10 (worst pain possible). The minimum clinically important difference (MCID) [12] for NRS that was used for calculation of the study sample size was 1.3 [18], although some authors suggest 1 [13] or 2 [5] are appropriate; if we had used an MCID of 2, the sample size would have been smaller. Secondary outcomes included NRS pain scores at rest, daily opioid use (postoperative day 1, 2, 7, 14), block duration, patient-oriented pain questions (postoperative day 1, 2, 7, 14), and patient and physician adherence to pathway. RESULTS: On postoperative day 1, pathway patients had lower worst pain with movement (3.3 ± 3.1) compared with control patients (5.6 ± 3.0, mean difference -2.7 [95% CI -3.7 to -1.7]; p < 0.001); lower scores were also seen for pain at rest (1.9 ± 2.3 versus 4.0 ± 2.9, mean difference -2.0 [95% CI -2.8 to -1.3]; p < 0.001). Cumulative postoperative opioid use (0-48 hours) was reduced (pathway oral morphine equivalent use was 23 ± 28 mg versus 44 ± 35 mg, mean difference 21 [95% CI 10 to 32]; p < 0.01). The greatest difference in opioid use was in the first 24 hours after surgery (pathway 7 ± 12 mg versus control 21 ± 21 mg, mean difference -14 [95% CI -19 to -10]; p < 0.01). On postoperative day 1, pathway patients had less interference with staying asleep compared with control patients (0.5 ± 1.6 versus 2.6 ± 3.3, mean difference -2.2 [95% CI -3.3 to -1.1]; p < 0.001); lower scores were also seen for interference with activities (0.9 ± 2.3 versus 1.9 ± 2.9, mean difference -1.1 [95% CI -2 to -0.1]; p = 0.03). Satisfaction with pain treatment on postoperative day 1 was higher among pathway patients compared with control patients (9.2 ± 1.7 versus 8.2 ± 2.5, mean difference 1.0 [95% CI 0.3 to 1.8]; p < 0.001). On postoperative day 2, pathway patients had lower nausea scores compared with control patients (0.3 ± 1.1 versus 1 ± 2.1, mean difference -0.7 [95% CI -1.2 to -0.1]; p = 0.02); lower scores were also seen for drowsiness on postoperative day 1 (1.7 ± 2.7 versus 2.6 ± 2.6, mean difference -0.9 [95% CI - 1.7 to -0.1]; p = 0.03). CONCLUSION: Adoption of the pathway was associated with improvement in the primary outcome (pain with movement) that exceeded the MCID. Patients in the pathway group had improved patient-oriented outcomes and fewer side effects. This pathway uses multiple analgesic drugs, which may pose risks to elderly patients, in particular. Therefore, in evaluating whether to use this pathway, clinicians should weigh the effect sizes against the potential risks that may emerge with large scale use, consider the difficulties involved in adapting a pathway to local practice so that pathway will persist, and recognize that this study only enrolled patients among surgeons and the anesthesiologists that advocated for the pathway; results may have been different with less enthusiastic clinicians. This pathway, based on a long-lasting nerve block, multimodal analgesia, and patient education can be considered for adoption. LEVEL OF EVIDENCE: Level II, therapeutic study.

A Diagnostic Algorithm for Posterior Fossa Tumors in Children: A Validation Study.

BACKGROUND AND PURPOSE: Primary posterior fossa tumors comprise a large group of neoplasias with variable aggressiveness and short and long-term outcomes. This study aimed to validate the clinical usefulness of a radiologic decision flow chart based on previously published neuroradiologic knowledge for the diagnosis of posterior fossa tumors in children. MATERIALS AND METHODS: A retrospective study was conducted (from January 2013 to October 2019) at 2 pediatric referral centers, Children's Hospital of Philadelphia, United States, and Great Ormond Street Hospital, United Kingdom. Inclusion criteria were younger than 18 years of age and histologically and molecularly confirmed posterior fossa tumors. Subjects with no available preoperative MR imaging and tumors located primarily in the brain stem were excluded. Imaging characteristics of the tumors were evaluated following a predesigned, step-by-step flow chart. Agreement between readers was tested with the Cohen κ, and each diagnosis was analyzed for accuracy. RESULTS: A total of 148 cases were included, with a median age of 3.4 years (interquartile range, 2.1-6.1 years), and a male/female ratio of 1.24. The predesigned flow chart facilitated identification of pilocytic astrocytoma, ependymoma, and medulloblastoma sonic hedgehog tumors with high sensitivity and specificity. On the basis of the results, the flow chart was adjusted so that it would also be able to better discriminate atypical teratoid/rhabdoid tumors and medulloblastoma groups 3 or 4 (sensitivity = 75%-79%; specificity = 92%-99%). Moreover, our adjusted flow chart was useful in ruling out ependymoma, pilocytic astrocytomas, and medulloblastoma sonic hedgehog tumors. CONCLUSIONS: The modified flow chart offers a structured tool to aid in the adjunct diagnosis of pediatric posterior fossa tumors. Our results also establish a useful starting point for prospective clinical studies and for the development of automated algorithms, which may provide precise and adequate diagnostic tools for these tumors in clinical practice.

The Feasibility of Outpatient Shoulder Arthroplasty: Risk Stratification and Predictive Probability Modeling.

Whether shoulder arthroplasty can be performed on an outpatient basis depends on appropriate patient selection. The purpose of this study was to identify risk factors for adverse events (AEs) following shoulder arthroplasty and to generate predictive models to improve patient selection. This was a retrospective review of prospectively collected data using a single institution shoulder arthroplasty registry as well as the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, including subjects undergoing hemiarthroplasty, total shoulder arthroplasty (TSA), and reverse TSA. Predicted probability of suitability for same-day discharge was calculated from multivariable logistic models for different patient subgroups based on age, comorbidities, and Charlson/Deyo Index scores. A total of 2314 shoulders (2079 subjects) in the institutional registry met inclusion criteria for this study. Younger age, higher body mass index (BMI), male sex, and prior steroid injection were all significantly associated with suitability for discharge, whereas preoperative narcotic use, comorbidities (heart disease and anemia/other blood disease), and Charlson/Deyo Index score of 2 were associated with AEs that might prevent same-day discharge. Compared with TSA, reverse TSA was associated with less suitability for discharge (P=.01). On querying the ACS-NSQIP database, 15,254 patients were identified. Female sex, BMI less than 35 kg/m2, American Society of Anesthesiologists class III/IV, preoperative anemia, functional dependence, low pre-operative albumin, and hemiarthroplasty were associated with unsuitability for discharge. Males 55 to 59 years old with no comorbidities nor history of narcotic use formed the lowest risk subgroup. Transfusion is the primary driver of AEs. Strategies to avoid this complication should be explored. Risk stratification will improve the ability to identify patients who can safely undergo outpatient shoulder arthroplasty. [Orthopedics. 2021;44(2):e215-e222.].

The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second-generation subtypes.

AIMS: Biomarker-driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub-classify iMB, and proffer strategies for personalized, risk-adapted therapies. METHODS: We characterized the iMB molecular landscape, including second-generation subtyping, and the associated retrospective clinical experience, using large independent discovery/validation cohorts (n = 387). RESULTS: iMBGrp3 (42%) and iMBSHH (40%) subgroups predominated. iMBGrp3 harboured second-generation subtypes II/III/IV. Subtype II strongly associated with large-cell/anaplastic pathology (LCA; 23%) and MYC amplification (19%), defining a very-high-risk group (0% 10yr overall survival (OS)), which progressed rapidly on all therapies; novel approaches are urgently required. Subtype VII (predominant within iMBGrp4 ) and subtype IV tumours were standard risk (80% OS) using upfront CSI-based therapies; randomized-controlled trials of upfront radiation-sparing and/or second-line radiotherapy should be considered. Seventy-five per cent of iMBSHH showed DN/MBEN histopathology in discovery and validation cohorts (P < 0.0001); central pathology review determined diagnosis of histological variants to WHO standards. In multivariable models, non-DN/MBEN pathology was associated significantly with worse outcomes within iMBSHH . iMBSHH harboured two distinct subtypes (iMBSHH-I/II ). Within the discriminated favourable-risk iMBSHH DN/MBEN patient group, iMBSHH-II had significantly better progression-free survival than iMBSHH-I , offering opportunities for risk-adapted stratification of upfront therapies. Both iMBSHH-I and iMBSHH-II showed notable rescue rates (56% combined post-relapse survival), further supporting delay of irradiation. Survival models and risk factors described were reproducible in independent cohorts, strongly supporting their further investigation and development. CONCLUSIONS: Investigations of large, retrospective cohorts have enabled the comprehensive and robust characterization of molecular heterogeneity within iMB. Novel subtypes are clinically significant and subgroup-dependent survival models highlight opportunities for biomarker-directed therapies.

Hydatid Disease With Pseudoaneurysm Formation of the Descending Thoracic Aorta.

Human Echinococcus disease is a zoonosis that primarily affects the liver and lungs. We report a rare case of hydatid disease in the posterior mediastinum with pseudoaneurysm formation of the descending thoracic aorta and erosion of thoracic vertebral bodies. The patient was surgically treated with removal of multiple daughter cysts and primary repair of the aorta.

Management of children with tuberculous broncho-esophageal fistulae.

INTRODUCTION: Broncho-esophageal fistula (BOF) is a rare complication of Mycobacterium tuberculosis (MTB). TB-associated BOF presents either as acute respiratory failure, aspiration pneumonia or as a complication of surgical decompression of thoracic lymph nodes. METHODS: All children with TB- associated BOF were included. TB was diagnosed if MTB was cultured from respiratory secretions, Ziehl-Neelsen (ZN) smear was positive, GeneXpert MTB/RIF was positive or a chest radiograph revealed radiographic features typical of TB. BOF was diagnosed by a contrast swallow study and/or flexible bronchoscopy. Chest computed tomography (CT) scan was performed, if required. RESULTS: Total of 20 children were diagnosed with TB-associated BOF between 1999 and 2019, with a 75% survival. A total of 85% BOF involved the left main bronchus. A total of 80% of patients were MTB culture or ZN smear-positive. Chest X-ray abnormalities included: extensive parenchymal disease (80%) and lymph gland enlargement (45%). CT features included visualization of the BOF (60%), esophageal air (73%) and pneumomediastinum (40%). BOF closure was achieved by surgical closure (46%), spontaneous closure (26%), fibrin glue (13%), and esophageal stent (13%). Multivariant regression analysis showed that C- reactive protein (CRP), albumin and CRP/albumin ratio were associated with mortality. CONCLUSION: Most TB-associated BOF are left-sided. It presents either acutely, with respiratory failure, or with chronic respiratory symptoms of aspiration. Children requiring invasive ventilation have high mortality. Most TB-associated BOF requires surgical intervention, although the use of fibrin glue offers an attractive alternative option.