Characterizing multiple sclerosis disease progression using a combined structural and functional connectivity metric.

PURPOSE: A combined resting state functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) metric called structural and functional connectivity index (SFCI) was recently proposed for tracking disease status and progression in multiple sclerosis (MS). The metric combines fcMRI and transverse diffusivity (TD) along different functional pathways involved in principle symptomatic domains of MS. In a longitudinal study of patients with MS receiving the same MS therapy, initial worsening of transcallosal (TC) motor and frontoparietal (FP) cognitive networks, as measured by fcMRI and DTI over the first year was followed by stabilization in the second year of follow-up. In this study we have (i) probed relationships between individual and composite neurological measures of MS with SFCI and its individual components along TC motor and FP cognitive pathways and (ii) compared sensitivity of SFCI to treatment-induced longitudinal changes with each individual imaging measure. METHODS: Twenty five patients with MS (15 female, age 42 ± 8 y) participated in this study and were scanned at 3 T whole body MRI scanner with diffusion tensor imaging (DTI) and resting-state functional connectivity MRI (fcMRI) scan protocol at baseline and 6, 12, 18 and 24 months after starting fingolimod. fcMRI and TD along TC and FP pathways were combined to form structural and functional connectivity index (SFCI) at each time point. Correlations between individual/combined neurological measures and individual imaging components/SFCI at baseline and were evaluated and compared. In addition, efficacies of individual and combined imaging metrics in tracking network integrity were compared. RESULTS: Individual TD along the TC pathway was significantly inversely correlated with all individual/composite neurological scores. There were moderate correlations of TC and FP components of SFCI with most of the neurological scores, and the pathway-combined SFCI was significantly correlated with all neurological scores. Trend-level increases of both TC and FP fcMRI were observed during the second year of follow-up, both TC and FP TD increased significantly in the first year and then stabilized during the second year. A trend toward a decrease in combined imaging metrics along TC and FP were observed during the first year, followed by a trend toward an increase in these metrics during the second year, while a significant decrease in SFCI during the first year followed by a significant increase during the second year was observed. CONCLUSIONS: SFCI was more effective in tracking network integrity/disease progression than individual pathway-specific components, which supports its use as an imaging marker for MS disease status and progression.

A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams.

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry.Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm-2depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in60Co applying the recommendations in the IAEA TRS-398 CoP.Main results.The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k= 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k= 1) for proton beams).Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Carbapenem-resistant Enterobacterales in patients with bacteraemia at tertiary academic hospitals in South Africa, 2019 - 2020: An update.

BACKGROUND: The emergence of carbapenem-resistant Enterobacterales (CRE) has become a serious and significant public health threat worldwide, owing to the limited antimicrobial therapy options, and the elevated mortality rates associated with these infections. OBJECTIVES: To present an update on the epidemiology of CRE bloodstream infections among hospitalised patients reported under the Group for Enteric, Respiratory and Meningeal Diseases Surveillance in South Africa (GERMS-SA) between January 2019 and December 2020. METHODS: Patients of all ages with CRE bacteraemia were included and isolates, when available, were sent to the reference laboratory for confirmatory testing and molecular characterisation. Multivariable logistic regression analysis was performed to assess factors associated with in-hospital mortality. RESULTS: We included 2 144 patients with CRE bacteraemia with a median age of 33 (interquartile range 1 - 51) years, of whom 1 145 (54.2%) were male. Klebsiella pneumoniae accounted for 79.8% of infections (n=863/1 082), of which 89.5% (n=611/683) were healthcare associated (HA). The most common carbapenemase genes were carbapenem-hydrolysing oxacillinase-48 (blaOXA-48-like) (76.8%; n=761/991), New Delhi metallo-ß-lactamase (blaNDM) (21.1%; n=209/991) and Verona integron-encoded metallo-ß-lactamase (blaVIM) (1.3%; n=13/991). None of the screened isolates with a colistin minimum inhibitory concentration >2 µg/mL harboured the mobilised colistin resistance (mcr)-1 to mcr-5 genes. The crude in-hospital mortality rate was 36.6% (n=377/1 029). Patients aged ≥60 years (v. 1.6 - 9 years) (adjusted odds ratio (aOR) 4.53; 95% confidence interval (CI) 2.21 - 9.28), those with comorbidities (diabetes, malignancy, renal and/or cardiovascular failure) (aOR 1.72; 95% CI 1.17 - 2.52), those with altered mental state (aOR 5.36; 95% CI 3.21 - 8.92) and those with previous antimicrobial use (aOR 1.88; 95% CI 1.27 - 2.77) had increased odds of in-hospital mortality. CONCLUSION: The epidemiology of CRE bloodstream infections remained similar compared with the previous surveillance report. Most infections were HA and caused by OXA-48-like carbapenemase-producing K. pneumoniae with no plasmid-mediated colistin resistance. Standard infection control measures should be strengthened.

Plastic bronchitis: A rare complication following a motor vehicle collision.

Plastic bronchitis, more appropriately termed chyloptysis, is a rare and potentially fatal condition caused by chylous coating of the airways. These cast coating can dislodge and become an obstructive mass in the patient's airway, necessitating rapid intervention. PB is well described to occur following single ventricle physiology heart disease corrective procedures, particularly following Fontan procedures. It is less commonly seen in traumatic settings. We present the youngest known case of a traumatic injury induced plastic bronchitis. A 19-year-old man was involved in a motor vehicle accident with airbag deployment. The airbags struck him in the chest; however, the patient felt well at the time and did not seek medical attention. Several months later the patient began coughing up milky white masses identified as casts. He was initially diagnosed with asthma but did not respond to therapy. He ultimately was found to have evidence of thoracic duct injury. Options for therapy were discussed, including possible thoracic duct ligation. The patient opted to continue a lowfat diet and has remained cast free. This case highlights the importance of considering plastic bronchitis in patients with cast production and a history of trauma to the chest.

Exploring neural correlates of behavioral and academic resilience among children in poverty.

Children in poverty must contend with systems that do not meet their needs. We explored what, at a neural level, helps explain children's resilience in these contexts. Lower coupling between lateral frontoparietal network (LFPN) and default mode network (DMN)-linked, respectively, to externally- and internally-directed thought-has previously been associated with better cognitive performance. However, we recently found the opposite pattern for children in poverty. Here, we probed ecologically-valid assessments of performance. In a pre-registered study, we investigated trajectories of network coupling over ages 9-13 and their relation to school grades and attention problems. We analyzed longitudinal data from ABCD Study (N = 8366 children at baseline; 1303 below poverty). The link between cognitive performance and grades was weaker for children in poverty, highlighting the importance of ecologically-valid measures. As predicted, higher LFPN-DMN connectivity was linked to worse grades and attentional problems for children living above poverty, while children below poverty showed opposite tendencies. This interaction between LFPN-DMN connectivity and poverty related to children's grades two years later; however, it was attenuated when controlling for baseline grades and was not related to attention longitudinally. Together, these findings suggest network connectivity is differentially related to performance in real-world settings for children above and below poverty.

Trauma-informed Approaches to Substance Use Interventions with Indigenous Peoples: A Scoping Review.

Indigenous Peoples experience disproportionately higher rates of problematic substance use. These problems are situated in a context of individual and intergenerational trauma from colonization, residential schools, and racist and discriminatory practices, policies, and services. Therefore, substance use interventions need to adopt a trauma-informed approach. We aimed to synthesize and report the current literature exploring the intersection of trauma and substance use interventions for Indigenous Peoples. Fourteen databases were searched using keywords for Indigenous Peoples, trauma, and substance use. Of the 1373 sources identified, 117 met inclusion criteria. Literature on trauma and substance use with Indigenous Peoples has increased in the last 5 years (2012-2016, n = 29; 2017-2021, n = 48), with most literature coming from the United States and Canada and focusing on historical or intergenerational trauma. Few articles focused on intersectional identities such as 2SLGBTQIA+ (n = 4), and none focused on veterans. There were limited sources (n = 25) that reported specific interventions at the intersection of trauma and substance use. These sources advocate for multi-faceted, trauma-informed, and culturally safe interventions for use with Indigenous Peoples. This scoping review illuminates gaps in the literature and highlights a need for research reporting on trauma-informed interventions for substance use with Indigenous Peoples.

Longitudinal wave attenuation in polycrystals with elongated grains: 3D numerical and analytical modeling.

This work develops a second-order approximation (SOA) model and a three-dimensional (3D) finite element (FE) model to calculate scattering-induced attenuation for elastic wave propagation in polycrystals with elongated grains of arbitrary crystal symmetry. The SOA model accounts for some degree of multiple scattering, whereas the 3D FE model includes all scattering possibilities. The SOA model incorporates the accurate geometric two-point correlation function obtained from the FE material systems to enable comparative studies between the two models. Also, the analytical Rayleigh and stochastic asymptotes are presented to provide explicit insights into propagation behaviors. Quantitative agreement is found between the FE and analytical models for all evaluated cases. In particular, the FE simulations support the SOA model prediction that grain shape does not exert influence on attenuation in the Rayleigh regime and its effect emerges as frequency increases to the stochastic regime showing anisotropy in attenuation. This attenuation anisotropy intensifies with the increase in frequency, but it exhibits a complicated behavior as frequency transits into the geometric regime. Wavefield fluctuations captured from the FE simulations are provided to help observe these complex scattering behaviors. The proportionality of attenuation to elastic scattering factors is also quantitatively evaluated.

Skin Toxicity Profile of Photon Radiotherapy versus Proton Beam Therapy in Paediatric and Young Adult Patients with Sarcomas.

AIMS: Radiotherapy is key in the management of patients with both Ewing sarcoma and rhabdomyosarcoma. However, there is little evidence in the literature with regards to radiation-induced skin toxicities (RISTs) for patients treated with conventional radiotherapy with X-rays (XRT) or proton beam therapy (PBT) for these two conditions. In the present study we evaluated acute and late RIST in patients treated within European protocols with either PBT or XRT, taking both clinical and dosimetric variables into consideration. MATERIALS AND METHODS: This was a retrospective analysis of 79 paediatric/young adult patients treated with radical radiotherapy (with XRT or PBT) and concurrent chemotherapy. In all cases, radiotherapy was given in conventional fractionation (1.8 Gy/fraction). Acute and late RISTs were registered according to the Radiation Therapy Oncology Group (RTOG) scoring system. RESULTS: With regards to acute RIST, 47.9% (23/48) of XRT patients and 48.4% (15/31) of PBT patients had acute grade 2/3 toxicity. When it comes to late RIST, 17.5% (7/40 with known toxicity profile) of XRT patients and 29.0% (9/31) of PBT patients had grade 1/2 toxicity. This difference of -11.5% (95% confidence interval -31.2 to 7.9%) in grade 1/2 toxicity between XRT and PBT was not statistically significant (P = 0.25). Regardless of the radiotherapy technique, V30Gy seems a good predictor of acute RIST. Moreover, for the same value of V30Gy, patients who receive PBT may have a higher risk of moderate-severe acute RIST. Perhaps due to the small sample, definitive conclusions on the predictive factors of late RIST could not be drawn. CONCLUSIONS: No clinically meaningful differences in acute and late RIST were observed between PBT and XRT subgroups. Systematic differences in the modelling of the build-up region may exist between XRT and PBT algorithms, which could make the comparison of dose metrics between techniques potentially biased. A more comprehensive analysis of dosimetric data on larger patient cohorts is needed to elucidate the most relevant skin dose metrics. Dose-effect models of RIST for this unique patient population would be an invaluable tool in radiotherapy plan optimisation.

Determining the parameter space for effective oxygen depletion for FLASH radiation therapy.

There has been a recent revival of interest in the FLASH effect, after experiments have shown normal tissue sparing capabilities of ultra-high-dose-rate radiation with no compromise on tumour growth restraint. A model has been developed to investigate the relative importance of a number of fundamental parameters considered to be involved in the oxygen depletion paradigm of induced radioresistance. An example eight-dimensional parameter space demonstrates the conditions under which radiation may induce sufficient depletion of oxygen for a diffusion-limited hypoxic cellular response. Initial results support experimental evidence that FLASH sparing is only achieved for dose rates on the order of tens of Gy s-1or higher, for a sufficiently high dose, and only for tissue that is slightly hypoxic at the time of radiation. We show that the FLASH effect is the result of a number of biological, radiochemical and delivery parameters. Also, the threshold dose for a FLASH effect occurring would be more prominent when the parameterisation was optimised to produce the maximum effect. The model provides a framework for further FLASH-related investigation and experimental design. An understanding of the mechanistic interactions producing an optimised FLASH effect is essential for its translation into clinical practice.

Long-term outcomes of index cryoballoon ablation or point-by-point radiofrequency ablation in patients with atrial fibrillation and systolic heart failure.

Catheter ablation is an established effective approach for the treatment of atrial fibrillation (AF) in patients with heart failure, however, the role of cryoablation in this setting is unclear. Procedural success and left ventricular systolic dysfunction (LVEF) improvement in patients with LVEF ≤ 45% undergoing index catheter ablation with cryoablation were evaluated. Freedom from AF recurrence was seen in 43% rising to 59% following repeat procedure. There were significant improvements in LVEF and functional status at long-term follow-up. Results were comparable to a contemporaneous cohort of heart failure patients undergoing index ablation with radiofrequency ablation. Cryoablation is an effective first-line AF ablation approach in the setting of heart failure.

The association between labour epidural case volume and the rate of accidental dural puncture.

Accidental dural puncture is a recognised complication of labour epidural placement and can cause a debilitating headache. We examined the association between labour epidural case volume and accidental dural puncture rate in specialist anaesthetists and anaesthesia trainees. We performed a retrospective cohort study of labour epidural and combined spinal-epidural nerve blocks performed between 1 July 2013 and 31 December 2017 at Waitemata District Health Board, Auckland, New Zealand. The mean (SD) annual number of obstetric epidural and combined spinal-epidural procedures for high-case volume specialists was 44.2 (15.0), and for low-case volume specialists was 10.0 (6.8), after accounting for caesarean section combined spinal-epidural procedures. Analysis of 7976 labour epidural and combined spinal-epidural procedure records revealed a total of 92 accidental dural punctures (1.2%). The accidental dural puncture rate (95%CI) in high-case volume specialists was 0.6% (0.4-0.9%) and in low-case volume specialists 2.4% (1.4-3.9%), indicating probable skill decay. The odds of accidental dural puncture were 3.77 times higher for low- compared with high-case volume specialists (95%CI 1.72-8.28, p = 0.001). Amongst trainees, novices had a significantly higher accidental dural puncture complication rate (3.1%) compared with registrars (1.2%), OR (95%CI) 0.39 (0.18-0.84), p = 0.016, or fellows (1.1%), 0.35 (0.16-0.76), p = 0.008. Accidental dural puncture complication rates decreased once trainees progressed past the 'novice' training stage.

Outcome of ACHD patients with non-inducible versus inducible IART undergoing cavo-tricuspid isthmus ablation: the role of empiric ablation.

PURPOSE: Catheter ablation for supraventricular tachycardia (SVT) in adults with congenital heart disease (ACHD) is an important therapeutic option. Cavo-tricuspid isthmus (CTI)-dependent intraatrial re-entrant tachycardia (IART) is common. However, induction of sustained tachycardia at the time of ablation is not always possible. We hypothesised that performing an empiric CTI line in case of non-inducibility leads to good outcomes. Long-term outcomes of empiric versus entrained CTI ablation in ACHD patients were examined. METHODS: Retrospective, single-centre, case-control study over 7 years. Arrhythmia-free survival after empiric versus entrained CTI ablation was compared. RESULTS: Eighty-seven CTI ablations were performed in 85 ACHD patients between 2010 and 2017. The mean age of the cohort was 43 years and 48% were male. Underlying aetiology included ASD (31%), VSD (11.4%), AVSD (9.1%), AVR (4.8%), Fallot's (18.4%), Ebstein's (2.3%), Fontan's palliation (9.2%) and atrial switch (13.8%). CTI-dependent IART was entrained in 59 patients whereas it was non-inducible in 28. The latter had an empiric CTI ablation. Forty-three percent of procedures were performed under general anaesthesia. There were no reported procedural complications. There was no significant difference in the mean procedure or fluoroscopy times between the groups (empiric vs entrained CTI; 169.1 vs 183.3 and 28.1 vs 19.9 min). Arrhythmia-free survival was 64.3% versus 72.8% (p value 0.44) in the empiric and entrained groups at 21 months follow-up. CONCLUSIONS: Long-term outcomes after empiric and entrained CTI ablation for IART in ACHD patients are comparable. This is a safe and effective therapeutic option. In the case of non-inducibility of IART, an empiric CTI line should be considered in this cohort.

Finite element evaluation of a simple model for elastic waves in strongly scattering elongated polycrystals.

A simple semi-analytical model for longitudinal scattering-induced attenuation and phase velocity is proposed for strongly scattering cubic polycrystals with statistically elongated grains. It is formulated by iterating the Born approximation of the far-field approximation model and by empirically increasing the coefficient in the quadratic term for the elastic scattering factor. The comparison with the three-dimensional grain-scale finite element calculations shows excellent performance of the semi-analytical model for both attenuation and phase velocity in all studied frequency ranges and especially in the Rayleigh regime in which, for strongly scattering materials, the existing analytical models significantly disagree with the numerical results.

Elastic wave velocity dispersion in polycrystals with elongated grains: Theoretical and numerical analysis.

The phase velocity dispersion of longitudinal waves in polycrystals with elongated grains of arbitrary crystallographic symmetry is studied in all frequency ranges by the theoretical second-order approximation (SOA) and numerical three-dimensional finite element (FE) models. The SOA and FE models are found to be in excellent agreement for three studied polycrystals: cubic Al, Inconel, and a triclinic material system. A simple Born approximation for the velocity, not containing the Cauchy integrals, and the explicit analytical quasi-static velocity limit (Rayleigh asymptote) are derived. As confirmed by the FE simulations, the velocity limit provides an accurate velocity estimate in the low-frequency regime where the phase velocity is nearly constant on frequency; however, it exhibits dependence on the propagation angle. As frequency increases, the phase velocity increases towards the stochastic regime and then, with further frequency increase, behaves differently depending on the propagation direction. It remains nearly constant for the wave propagation in the direction of the smaller ellipsoidal grain radius and decreases in the grain elongation direction. In the Rayleigh and stochastic frequency regimes, the directional velocity change shows proportionalities to the two elastic scattering factors even for the polycrystal with the triclinic grain symmetry.

Maximizing the accuracy of finite element simulation of elastic wave propagation in polycrystals.

Three-dimensional finite element (FE) modelling, with representation of materials at grain scale in realistic sample volumes, is capable of accurately describing elastic wave propagation and scattering within polycrystals. A broader and better future use of this FE method requires several important topics to be fully understood, and this work presents studies addressing this aim. The first topic concerns the determination of effective media parameters, namely, scattering induced attenuation and phase velocity, from measured coherent waves. This work evaluates two determination approaches, through-transmission and fitting, and it is found that these approaches are practically equivalent and can thus be used interchangeably. For the second topic of estimating modelling errors and uncertainties, this work performs thorough analytical and numerical studies to estimate those caused by both FE approximations and statistical considerations. It is demonstrated that the errors and uncertainties can be well suppressed by using a proper combination of modelling parameters. For the last topic of incorporating FE model information into theoretical models, this work presents elaborated investigations and shows that to improve agreement between the FE and theoretical models, the symmetry boundary conditions used in FE models need to be considered in the two-point correlation function, which is required by theoretical models.

Changes in structural and functional connectivity during two years of fingolimod therapy for multiple sclerosis.

BACKGROUND: Fingolimod, an oral drug, has been reported to reduce relapse rate in multiple sclerosis (MS). However disease progression may still occur in spite of control of inflammation. Functional imbalances within and between cerebral networks associated with disruption of structural and functional network integrity, have been reported in MS. An effective therapy is expected to stabilize such functional network integrity. OBJECTIVE: The purpose of this study was to investigate changes in structural and resting-state functional connectivity of motor and cognitive networks, and associated changes in neurologic scores in MS, during 2 years of fingolimod therapy. METHODS: Twenty five subjects with MS were recruited for this study. Subjects were scanned with diffusion tensor imaging (DTI) and resting-state functional connectivity MRI (fcMRI) scan protocol at 3 T with 6-month interval over a period of 2 years. Neurologic performance scores of motor and cognitive performances were also obtained. RESULTS: DTI measures worsened during the 1st year and then stabilized; any trend of stabilization of fcMRI was delayed until the 2nd year. While motor performance did not change, cognitive performance showed improvement. Several baseline DTI measures correlated with relevant neurologic scores. CONCLUSION: Initial worsening of motor and cognitive network was reported after 1 year of treatment, but seems DTI and fcMRI measures seem to stabilize after around one year fingolimod therapy.

A multisectoral investigation of a neonatal unit outbreak of Klebsiella pneumoniae bacteraemia at a regional hospital in Gauteng Province, South Africa.

BACKGROUND: Rates of healthcare-associated infections (HAIs) among babies born in developing countries are higher than among those born in resource-rich countries, as a result of suboptimal infection prevention and control (IPC) practices. Following two reported deaths of neonates with carbapenem-resistant Klebsiella pneumoniae bloodstream infections (BSIs), we conducted an outbreak investigation in a neonatal unit of a regional hospital in Gauteng Province, South Africa. OBJECTIVES: To confirm an outbreak of K. pneumoniae BSIs and assess the IPC programme in the neonatal unit. METHODS: We calculated total and organism-specific BSI incidence risks for culture-confirmed cases in the neonatal unit for baseline and outbreak periods. We conducted a clinical record review for a subset of cases with K. pneumoniae BSI that had been reported to the investigating team by the neonatal unit. An IPC audit was performed in different areas of the neonatal unit. We confirmed species identification and antimicrobial susceptibility, and used polymerase chain reaction for confirmation of carbapenemase genes and pulsed-field gel electrophoresis (PFGE) for typing of submitted clinical isolates. RESULTS: From January 2017 to August 2018, 5 262 blood cultures were submitted, of which 11% (560/5 262) were positive. Of 560 positive blood cultures, 52% (n=292) were positive for pathogenic organisms associated with healthcare-associated BSIs. K. pneumoniae comprised the largest proportion of these cases (32%; 93/292). The total incidence risk of healthcare-associated BSI for the baseline period (January 2017 - March 2018) was 6.8 cases per 100 admissions, and that for the outbreak period (April - September 2018) was 10.1 cases per 100 admissions. The incidence risk of K. pneumoniae BSI for the baseline period was 1.6 cases per 100 admissions, compared with 5.0 cases per 100 admissions during the outbreak period. Average bed occupancy for the entire period was 118% (range 101 - 133%), that for the baseline period was 117%, and that for the outbreak period was 121%. In a subset of 12 neonates with K. pneumoniae bacteraemia, the median (interquartile range (IQR)) gestational age at birth was 27 (26 - 29) weeks, and the median (IQR) birth weight was 1 100 (880 - 1 425) g. Twelve bloodstream and 31 colonising K. pneumoniae isolates were OXA-48-positive. All isolates were genetically related by PFGE analysis (89% similarity). Inadequate IPC practices were noted, including suboptimal adherence to aseptic technique and hand hygiene (57% overall score in the neonatal intensive care unit), with poor monitoring and reporting of antimicrobial use (pharmacy score 55%). CONCLUSIONS: Overcrowding and inadequate IPC and antimicrobial stewardship contributed to a large outbreak of BSIs caused by genetically related carbapenemase-producing K. pneumoniae isolates in the neonatal unit.

Stabilization of Metastatic Uterine Leiomyosarcoma Using Pembrolizumab.

The estimated 5-year survival rate for patients with stage IV uterine leiomyosarcoma is 29%, with a median survival of <1 year. This report describes a patient with stage IVB leiomyosarcoma who experienced stable disease for 15 months on pembrolizumab. A woman aged 62 years, gravida 2 para 2, with postmenopausal bleeding and a necrotic uterine fibroid underwent a dilation and curettage and was diagnosed with uterine leiomyosarcoma. CT imaging showed pulmonary and bony metastasis. She underwent surgical staging with biopsy-proved stage IVB disease. A mixed partial response was noted using first- and second-line chemotherapy. Molecular tumor profiling confirmed PD-L1 expression. The patient was started on pembrolizumab, and at the time of writing she is status post 23 cycles with stable disease. Pembrolizumab was well tolerated and aided prolonged disease stabilization.

Correction to: Merkel Cell Carcinoma Outcomes: Does AJCC8 Underestimate Survival?

C.R. Farley and M.C. Perez contributed equally to this publication and are co-first authors. J.S. Zager and M.C. Lowe contributed equally to this publication and are co-corresponding authors.