Outcomes of Prophylactic Peritoneal Dialysis Catheter Insertion in Children Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES: The objective of this Prospective Register of Systematic Reviews (CRD42022384192) registered systematic review and meta-analysis was to determine whether prophylactic peritoneal dialysis (PD) catheter insertion at the time of pediatric cardiac surgery is associated with improved short-term outcomes. DATA SOURCES: Databases search of the MEDLINE, EMBASE, CINAHL, and Cochrane Library completed in April 2021 and updated October 2023. STUDY SELECTION: Two reviewers independently completed study selection, data extraction, and bias assessment. Inclusion criteria were randomized controlled trials (RCTs) and observational studies of children (≤ 18 yr) undergoing cardiac surgery with cardiopulmonary bypass. We evaluated use of prophylactic PD catheter versus not. DATA EXTRACTION: The primary outcome was in-hospital mortality, as well as secondary short-term outcomes. Pooled random-effect meta-analysis odds ratio with 95% CI are reported. DATA SYNTHESIS: Seventeen studies met inclusion criteria, including four RCTs. The non-PD catheter group received supportive care that included diuretics and late placement of PD catheters in the ICU. Most study populations included children younger than 1 year and weight less than 10 kg. Cardiac surgery was most commonly used for arterial switch operation. In-hospital mortality was reported in 13 studies; pooled analysis showed no association between prophylactic PD catheter placement and in-hospital mortality. There were mixed results for ICU length of stay and time to negative fluid balance, with some studies showing shortened duration associated with use of prophylactic PD catheter insertion and others showing no difference. Overall, the studies had high risk for bias, mainly due to small sample size and lack of generalizability. CONCLUSIONS: In this meta-analysis, we have failed to demonstrate an association between prophylactic PD catheter insertion in children and infants undergoing cardiac surgery and reduced in-hospital mortality. Other relevant short-term outcomes, including markers of fluid overload, require further study.

Predictors of NIV-related adverse events in children using long-term noninvasive ventilation.

BACKGROUND AND OBJECTIVES: An increasing number of children with diverse medical conditions are using long-term noninvasive ventilation (NIV). This study examined the impact of demographic, clinical, and technology-related factors on long-term NIV adverse events in a large cohort of children using long-term NIV. METHODS: This was a multicenter retrospective review of all children who initiated long-term NIV in the province of Alberta, Canada, from January 2005 to September 2014, and followed until December 2015. Inclusion criteria were children who had used NIV for 3 months or more and had at least one follow-up visit with the NIV programs. RESULTS: We identified 507 children who initiated NIV at a median age of 7.5 (interquartile range: 8.6) years and 93% of them reported at least one NIV-related adverse event during the initial follow-up visit. Skin injury (20%) and unintentional air leaks (19%) were reported more frequently at the initial visit. Gastrointestinal symptoms, midface hypoplasia, increased drooling, aspiration and pneumothorax were rarely reported (<5%). Younger age and underlying conditions such as Down syndrome, achondroplasia, and Duchenne muscular dystrophy were early predictors of unintentional air leak. Younger age also predicted child sleep disruption in the short term and ongoing parental sleep disruption. Obesity was a risk factor for persistent nasal symptoms. Mask type was not a significant predictor for NIV-related short- or long-term complications. CONCLUSIONS: This study demonstrates that NIV-related complications are frequent. Appropriate mask-fitting and headgear adaptation, and a proactive approach to early detection may help to reduce adverse events.

Mortality and bleeding associated with the management of sub-massive pulmonary embolism: a systematic review and Bayesian network meta-analysis.

Current guidelines recommend anticoagulation (AC) for low and intermediate-risk pulmonary embolism (PE) and systemic thrombolysis (tPA) for high risk (massive) PE. How these treatment options compare with other modalities of treatment such as catheter directed thrombolysis (CDT), ultrasound assisted catheter thrombolysis (USAT), and administering lower dose of thrombolytics (LDT) is unclear. There is no study that has compared all these treatment options. We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials in patients with submassive (intermediate risk) PE. Fourteen randomized controlled trials were included, comprising 2132 patients. On Bayesian network meta-analysis, a significant decrease in mortality was noted in tPA versus AC. There was no significant difference between USAT versus CDT. For risk of major bleeding, there was no significant difference in relative risk of major bleeding between tPA versus AC and USAT versus CDT. tPA was found to have a significantly higher risk of minor bleeding and a lower risk of recurrent PE compared to AC. Systemic thrombolysis is associated with a significant reduction in mortality and recurrent PE compared to anticoagulation but an increased risk of minor bleeding. There was no difference in risk of major bleeding. Our study also shows that while the newer modalities of treatment for pulmonary embolism are promising, there is lack of data to comment on the purported advantages.

Respiratory characteristics in children with spinal muscular atrophy type 1 receiving nusinersen.

BACKGROUND: Spinal muscular atrophy type 1 (SMA1) is a neuromuscular disorder with a natural history of chronic respiratory failure and death during infancy without ventilation. Recently, disease-modifying therapies such as nusinersen have improved disease trajectory. However, objective data on the trajectory of polysomnography outcomes, the relationship between motor scores and respiratory parameters, respiratory technology dependence and healthcare utilization in children with SMA1 remain to be elucidated. METHODS: This was a retrospective observational study of children with SMA1 receiving nusinersen between October 2016 and February 2021 at two tertiary care hospitals in Canada. Baseline polysomnography data, motor scores, respiratory technology, and unanticipated healthcare utilization were examined. RESULTS: Eleven children (five females, two SMN2 copies each) were included. Median (interquartile range [IQR]) age at diagnosis was 3.6 (2.8-5.0) months and age at diagnostic polysomnogram following nusinersen initiation was 9.4 (5.3-14.0) months. Nusinersen was initiated at a median (IQR) age of 5.4 (3.4-7.6) months and 8/11 children had respiratory symptoms at that time. Diagnostic polysomnography data showed a median (IQR) central apnea-hypopnea index (AHI) of 4.1 (1.8-10.0) and obstructive AHI of 2.2 (0-8.0) events/h. We observed an inverse relationship between motor scores and central apnea-hypopnea indices. All children required ventilatory support at the end of the study period. CONCLUSION: This study showed abnormal polysomnography parameters and need for ventilation despite nusinersen suggesting ongoing need for regular monitoring with polysomnography. Understanding the respiratory disease trajectory of children undergoing treatment with nusinersen will inform decision-making regarding optimal timing of ventilatory support initiation.

Impact of COVID-19 pandemic on adherence to noninvasive ventilation in children.

STUDY OBJECTIVES: The aim of this study was to measure changes in adherence to noninvasive ventilation (NIV) in children during the first year of the COVID-19 pandemic. METHODS: Retrospective chart review of children (0-18 years) using home NIV through the Stollery's Pediatric NIV program in Edmonton, Canada during March 2019 to March 2021. Demographics, clinical characteristics, and adherence information from machine downloads were collected prior to and during the first year of the COVID-19 pandemic. Paired t tests and Chi-square compared adherence prepandemic and during pandemic and repeated analysis of variance tests compared adherence pre- and 0-6 and 6-12 months during pandemic. RESULTS: Eighty-two children met inclusion criteria (62% male; age 8.6 ± 4.6 years). Overall, there were no changes in NIV adherence during pandemic (average NIV minutes pre- and during pandemic of 390 ± 219 and 405 ± 300 minutes, respectively). When separated into increased vs decreased adherence groups, adherence differences pre- compared to during pandemic became significant, with no differences across demographic/clinical variables or prepandemic adherence. There were no changes in NIV adherence during the initial 6 months of pandemic compared to prepandemic, but NIV use significantly increased by 9-57 minutes during the following 6-12 months. Bilevel positive airway users had longer NIV use than continuous positive airway pressure users at all time points, with an overall increasing trend over time. CONCLUSIONS: Despite the significant life disruption created by COVID-19 and changes to virtual care, children using home NIV maintained adequate adherence. Qualitative research is needed to understand the nuances of using NIV during the pandemic and potential advantages of virtual care for support of these children and families. CITATION: Halperin H, Chalifour M, Bedi PK, et al. Impact of COVID-19 pandemic on adherence to noninvasive ventilation in children. J Clin Sleep Med. 2023;19(1):179-188.

Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection : Meta-analysis of Randomized Controlled Trials.

GOALS: The aim was to assess the effectiveness of fecal microbiota transplantation (FMT) against medical therapy (MT). BACKGROUND: FMT has shown good outcomes in the treatment of Clostridium difficile infection (CDI). We aimed to conduct a systematic review and meta-analysis to compare the effectiveness of FMT versus MT for CDI. STUDY: We performed a comprehensive search to identify randomized controlled trials comparing FMT against MT in patients with CDI. Outcomes of interest were clinical cure as determined by the resolution of diarrhea and/or negative C. difficile testing. Primary CDI is defined as the first episode of CDI confirmed endoscopically or by laboratory analysis. Recurrent C. difficile infection (RCDI) is defined as laboratory or endoscopically confirmed episode of CDI after at least 1 course of approved antibiotic regimen. RESULTS: A total of 7 studies with 238 patients were included in meta-analysis. Compared with MT, FMT did not have a statistically significant difference for clinical cure of combined primary and RCDI after first session [risk ratio (RR): 1.52, 95% confidence interval (CI): 0.90, 2.58; P =0.12; I2 =77%] and multiple sessions of FMT (RR: 1.68; CI: 0.96, 2.94; P =0.07; I2 =82%). On subgroup analysis, FMT has statistically higher rate of response than MT (RR: 2.41; CI: 1.20, 4.83; I2 =78%) for RCDI. However, for primary CDI there is no statistically significant difference between FMT and MT (RR: 1.00; CI: 0.72, 1.39; I2 =0%). CONCLUSION: As per our analysis, FMT should not be utilized for every patient with CDI. It is more effective in RCDI, but the results were not significant in patients with primary CDI.

Outcomes of Long-Term Noninvasive Ventilation Use in Children with Neuromuscular Disease: Systematic Review and Meta-Analysis.

Objectives: To determine whether children with neuromuscular disorders using long-term noninvasive ventilation (NIV), continuous or bilevel positive airway pressure, have improved health outcomes compared with alternative treatment strategies. Data Sources: This systematic review is an extension of a scoping review. The search strategy used Medical Subject Headings and free-text terms for "child" and "noninvasive ventilation." Studies of humans from 1990 onward were searched in MEDLINE (Ovid), Embase (Ovid), CINAHL (Ebsco), Cochrane Library (Wiley), and PubMed. The results were reviewed for articles reporting on neuromuscular disorders and health outcomes including mortality, hospitalization, quality of life, lung function, sleep study parameters, and healthcare costs. Data Extraction: Extracted data included study design, study duration, sample size, age, type of NIV, follow-up period, primary disease, and primary and secondary outcome measures. Studies were grouped by primary disease into three groups: spinal muscular atrophy, Duchenne muscular dystrophy, and other/multiple neuromuscular diseases. Data Synthesis: A total of 50 articles including 1,412 children across 36 different neuromuscular disorders are included in the review. Mortality is lower for children using long-term NIV compared with supportive care across all neuromuscular disease types. Overall, mortality does not differ when comparing the use of NIV with invasive mechanical ventilation, though heterogeneity suggests that mortality with NIV is higher for spinal muscular atrophy type 1 and lower for other/multiple neuromuscular diseases. The impact of long-term NIV on hospitalization rate differed by neuromuscular disease type with lower rates compared with supportive care but higher rates compared with supportive care use for spinal muscular atrophy type 1, and lower rates compared with before NIV for other/multiple neuromuscular diseases. Overall, lung function was unaltered and sleep study parameters were improved from baseline by long-term NIV use. There are few data to assess the impact of long-term NIV use on quality of life and healthcare costs. Conclusions: Long-term NIV for children provides benefit for mortality, hospitalizations, and sleep study parameters for some sub-groups of children with neuromuscular disorders. High risk of bias and low study quality preclude strong conclusions.

A rare case of Levofloxacin-related Iliopsoas and Achilles tendon rupture.

Achilles tendon rupture is a well-documented adverse effect of Fluoroquinolones; however, herein we present a case of complete iliopsoas and Achilles, and partial semimembranosus tendon rupture secondary to Levofloxacin.

Pattern and burden of opioid-related hospitalizations in the USA from 2016 to 2018.

AIMS: The current opioid crisis in the USA is a formidable challenge for the healthcare system, and the general population. Our objective is to characterize the burden of opioid-related disorders in an inpatient setting in the USA for the years 2016, 2017 and 2018 using the National Inpatient Sample (NIS). METHODS: A cross-sectional analysis of the NIS was performed to identify and analyse hospitalizations with an opioid-related diagnosis in 2016, 2017 and 2018. Descriptive statistics and regression models were utilized to define the demographics of the population of interest and measure the outcomes. RESULTS: We identified 962 900 discharges with opioid-related diagnosis in 2016, 982 710 in 2017 and 942 110 in 2018. The majority were age <60 years, were found in residents of low-income zip codes and covered by Medicaid. The adjusted mean total hospitalization cost trended up from $12 828 (95% confidence interval [CI] 12 547-13 108) in 2016, to $13164.9 (95% CI 12 872.47-13 457.34) in 2017 and then to $13 626.65 (95% CI 13 325.95-13 927.34) in 2018. The adjusted mortality was highest in 2016; 2.26% (95% CI 2.16-2.35) and it trended down to 1.97% (95% CI 1.88-2.05) in 2017, and to 1.89% (95% CI 1.81-1.98) in 2018. CONCLUSIONS: Opioid-related disorders cause a significant number of hospitalizations in the USA. A large proportion of these patients are age <60 years, have lower household income, and are covered by Medicaid. Programmes directed towards this specific group can help reduce the overall burden of hospitalizations.

Predictors of longitudinal outcomes for children using long-term noninvasive ventilation.

BACKGROUND: Noninvasive ventilation (NIV) is a first-line therapy for sleep-related breathing disorders and chronic respiratory insufficiency. Evidence about predictors that may impact long-term NIV outcomes, however, is scarce. The aim of this study is to determine demographic, clinical, and technology-related predictors of long-term NIV outcomes. METHODS: A 10-year multicentred retrospective review of children started on long-term continuous or bilevel positive airway pressure (CPAP or BPAP) in Alberta. Demographic, technology-related, and longitudinal clinical data were collected. Long-term outcomes examined included ongoing NIV use, discontinuation due to improvement in underlying conditions, switch to invasive mechanical ventilation (IMV) or death, patient/family therapy declination, transfer of services, and hospital admissions. RESULTS: A total of 622 children were included. Both younger age and CPAP use predicted higher likelihood for NIV discontinuation due to improvement in underlying conditions (p < .05 and p < .01). Children with upper airway disorders or bronchopulmonary dysplasia were less likely to continue NIV (p < .05), while presence of central nervous system disorders had a higher likelihood of hospitalizations (p < .01). The presence of obesity/metabolic syndrome and early NIV-associated complications predicted higher risk for NIV declination (p < .05). Children with more comorbidities or use of additional therapies required more hospitalizations (p < .05 and p < .01) and the latter also predicted higher risk for being switched to IMV or death (p < .001). CONCLUSIONS: Demographic, clinical data, and NIV type impact long-term NIV outcomes and need to be considered during initial discussions about therapy expectations with families. Knowledge of factors that may impact long-term NIV outcomes might help to better monitor at-risk patients and minimize adverse outcomes.

The value of coronal DWI in brainstem stroke diagnosis.

Acute brainstem strokes can present a diagnostic challenge due to its variable clinical presentation. MRI with diffusion-weighted (axial) imaging is highly sensitive for diagnosing ischemic lesions however even that can fail to identify early lesions in the brainstem. Combining coronal section to standard axial MRI-DWI can facilitate early diagnosis in these cases.

Updates in Treatment of Recurrent Clostridium difficile Infection.

Recurrent Clostridium difficile infection (CDI) is a perpetual problem that leads to increased economic burden, higher healthcare cost, and significant morbidity and mortality. Its treatment remains a challenge. While various treatment approaches have been attempted with different levels of success, robust data establishing the superiority of one approach over the others is lacking. In this article, we review the current evidence pertaining to conventional pharmacological treatment as well as fecal microbiota transplantation (FMT) as a novel, rapidly emerging treatment modality for recurrent CDI.

Chimeric Antigen Receptor T-Cells: The Future is Now.

The immune system acting via cancer immune-surveillance is considered a potential target for improving outcomes among some malignancies. The ability to harness immune cells, engineer them and educate them to target cancer cells has changed the paradigm for treating non-Hodgkin's lymphomas (NHL) and acute lymphoblastic leukemia (ALL). Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable anti-tumor activity against refractory B cell malignancies. Ongoing research aims to expand the scope of this adoptive cell therapy, understanding mechanisms of resistance and reducing toxicity. In this review, we will discuss the current scope of CAR T-cell therapy and ongoing future applications.

Paroxysmal Sympathetic Hyperactivity after Cardiac Arrest in a Young Male.

Paroxysmal sympathetic hyperactivity (PSH) is a syndrome of an increased sympathetic drive after brain injury. PSH has been previously referred with multiple different names. It is seen most commonly after a traumatic brain injury, but rarely it has been reported after infections, brain malignancies, and brain injury after cardiac arrest. We present a case of a young male who developed PSH after cardiac arrest and will discuss clinical features and various management options.

Angioimmunoblastic T-cell lymphoma: a rare subtype of peripheral T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of NHL and usually presents in the late stage due to the atypical laboratory findings. Immunohistochemistry of the lymph node in AITL is characterized by positive CD2, CD3, CD4, CD10, CXCL-13, PD1 often BCL-6 and CD20 positive. Meshworks of follicular dendritic cells are seen outside follicles with CD21 and CD23 stains. EBV can be often positive as well. Autologous transplantation should be offered in the first remission as poor outcome is reported with anthracycline-containing regimens.

Blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm is an aggressive neoplasm with a median survival of only a few months despite treatment. An exhaustive immunohistochemical workup is required to differentiate it from myeloid sarcoma and extranodal NK/T cell lymphoma. Treatment is with induction using a regimen utilized for leukemia. Allogeneic hematopoietic stem cell transplantation is recommended for those who achieve remission following induction.

CK 20-positive and CK 7-negative Merkel cell carcinoma of the cheek.

Merkel cell carcinomas (MCCs) are uncommon, highly malignant skin tumors that develop in sun-exposed areas of the skin. Most of the MCCs are CK 20-positive and CK 7-negative such as our case. About 80% of Merkel cell carcinoma is associated with Merkel cell polyomavirus.

Long-term Non-Invasive Ventilation in Infants: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of long-term non-invasive ventilation (NIV) to treat sleep and breathing disorders in children has increased substantially in the last decade; however, less data exist about its use in infants. Given that infants have distinct sleep and breathing patterns when compared to older children, the outcomes of infants on long-term NIV may differ as well. The aim of this study is to systematically review the use and outcomes of long-term NIV in infants. METHODS: Ovid Medline, Ovid Embase, CINAHL (via EbscoHOST), PubMed, and Wiley Cochrane Library were systematically searched from January 1990 to July 2017. Studies on infants using long-term NIV outside of an acute care setting were included. Data were extracted on study design, population characteristics, and NIV outcomes. RESULTS: A total of 327 studies were full-text reviewed, with final inclusion of 60. Studies were distributed across airway (40%), neuromuscular (28%), central nervous system (10%), cardio-respiratory (2%), and multiple (20%) disease categories. Of the 18 airway studies reporting on NIV outcomes, 13 (72%) reported improvements in respiratory parameters. Of the 12 neuromuscular studies exclusively on spinal muscular atrophy type 1 (SMA1), six (50%) reported decreased hospitalizations and nine (75%) reported on mortality outcomes. Risk of bias was moderate to serious, and quality of the evidence was low to very low for all studies. Most studies had an observational design with no control group, limiting the potential for a meta-analysis. CONCLUSION: The outcomes reported in studies differed by the disease category being studied. Studies on airway conditions showed improvements in respiratory parameters for infants using NIV. Studies on neuromuscular disorder, which were almost exclusively on SMA1, reported decreased hospitalizations and prolonged survival. Overall, it appears that NIV is an effective long-term therapy for infants. However, the high risk of bias and low quality of the available evidence limited strong conclusions.

Hepatotoxicity Associated With Vismodegib.

An 82-year-old Caucasian woman with a history of basal cell carcinoma on vismodegib presented with nausea, vomiting and intermittent abdominal pain. Laboratory results were remarkable for the elevation of liver enzymes. Endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiogram (PTC) did not show evidence of intrahepatic or extrahepatic obstruction of the biliary tract. During PTC external biliary catheter was placed; however, bilirubin continued to rise. Further, laboratory work-up and imaging studies ruled out other possible aetiologies for hepatotoxicity such as infections, autoimmune hepatitis and other drugs known to be hepatotoxic thus leaving vismodegib the most likely cause of hepatotoxicity.