Characterization of initial CLABSI culture results to support antimicrobial de-escalation in pediatric GI inpatients.

OBJECTIVES: Central Line-associated Bloodstream Infections (CLABSIs) pose a serious mortality and morbidity risk. An institutional protocol was developed for the evaluation and empirical antibiotic treatment of possible CLABSIs. The potential impact of de-escalating antimicrobial therapy based on initial Gram stain and molecular identification was assessed. METHODS: All positive blood cultures from patients admitted to the gastroenterology service at a large pediatric medical center were collected from 1/1/14 to 12/31/20. Cultures that were negative, repeated, or causative organisms that were unable to be identified with susceptibility data were excluded. Timepoints and organism(s) from each culture were recorded. Polymicrobial cultures were classified as containing only gram-positive organisms (polymicrobial GP), only gram-negative organisms (polymicrobial GN), or mixed spectrum. RESULTS: During the 6-year period, 361 positive blood cultures were included in the study. Single isolates were identified in 79.5% (287/361) of cultures. Polymicrobial cultures from confirmed central line source accounted for 15.0% (54/361), with 6.4% (23/361) Polymicrobial GP, 4.4% (16/361) Polymicrobial GN, and 4.2% (15/361) being mixed-spectrum cultures. Both organism types were detected on initial gram-stain in 40% (6/15) of the mixed-spectrum cultures, another 26.7% (4/15) had the opposite-spectrum organism identified within an average of <3 h and the remaining 33.3% (5/15) had the opposite-spectrum organism identified by culture growth. CONCLUSIONS: Polymicrobial mixed-spectrum cultures accounted for <5% of positive blood cultures and most isolates were identified within 3 h of first positivity. This may allow for further investigation of early de-escalation of therapy for this population and limit antimicrobial exposure.

Chronic Mucosal Inflammation in Pediatric Intestinal Failure Patients-A Unique Phenomenon.

INTRODUCTION/OBJECTIVES: As intestinal failure (IF) management improves and long-term survival rate increases, its physiological complications have become more apparent. The development of chronic intestinal inflammation resembling inflammatory bowel disease (IBD) in this population has been reported, but the literature describing it in detail is sparse. The present study was designed to characterize children with IF who developed chronic intestinal inflammation and identify the potential predisposing clinical factors. METHODS: This retrospective study was based on the electronic medical records of pediatric patients seen at the Cincinnati Children's Hospital Medical Center between January 2000 and July 2022. Demographic and medical history data were collected and compared between children with IF that developed chronic intestinal inflammation and children with IF that did not develop chronic intestinal inflammation. RESULTS: During the follow-up period, 23 children were diagnosed with chronic intestinal inflammation. Of these, 12 (52%) were males, with a median age of 4.5 (3-7) years at diagnosis. Nearly one-third of the patients had gastroschisis (31%), followed by necrotizing enterocolitis (26%), and malrotation and volvulus (21.7%). More children in the chronic intestinal inflammation group lacked an ileocecal valve (ICV) and adjoining distal ileum as compared to the short bowel syndrome (SBS)-IF control group (15 patients, 65% vs 8 patients, 33%). Moreover, more children in the chronic intestinal inflammation group had undergone a prior lengthening procedure than the SBS-IF control group (5 patients, 21.7% vs. 0, respectively). DISCUSSION: SBS patients are at risk of relatively early onset chronic intestinal inflammation. The absence of an ICV (and adjoin ileum) and prior lengthening procedures emerge as factors associated with the risk of IBD in these patients.

[Rare diseases in the differential diagnosis of myalgia]. / Seltene Erkrankungen in der Differenzialdiagnose bei Myalgien.

Myalgia describes pain in the skeletal muscles. According to the current German clinical guidelines from 2020 (AWMF register number: 030/051), the initial diagnostic assessment consists of the anamnesis, clinical examination, electrophysiological examination and standard laboratory tests. Additional special examinations, such as molecular genetic investigations, special laboratory tests, medical imaging and muscle biopsy are only needed in certain cases. This article focuses on rare neurological diseases that are classically associated with myalgia. In this context etiologically different diseases are considered, whereby some genetically linked diseases (fascioscapulohumeral dystrophy, FSHD, dystrophia myotonica, McArdle's disease, Pompe's disease, limb girdle muscular dystrophy) are contrasted with diseases with an (auto)immune-related pathogenesis (stiff-person syndrome, Isaacs syndrome). The aspects relevant for the diagnosis are particularly highlighted. The therapeutic aspects of the diseases are not part of this article.

[Rare diseases in the differential diagnosis of myalgia]. / Seltene Erkrankungen in der Differenzialdiagnose bei Myalgien.

Myalgia describes pain in the skeletal muscles. According to the current German clinical guidelines from 2020 (AWMF register number: 030/051), the initial diagnostic assessment consists of the anamnesis, clinical examination, electrophysiological examination and standard laboratory tests. Additional special examinations, such as molecular genetic investigations, special laboratory tests, medical imaging and muscle biopsy are only needed in certain cases. This article focuses on rare neurological diseases that are classically associated with myalgia. In this context etiologically different diseases are considered, whereby some genetically linked diseases (fascioscapulohumeral dystrophy, FSHD, dystrophia myotonica, McArdle's disease, Pompe's disease, limb girdle muscular dystrophy) are contrasted with diseases with an (auto)immune-related pathogenesis (stiff-person syndrome, Isaacs syndrome). The aspects relevant for the diagnosis are particularly highlighted. The therapeutic aspects of the diseases are not part of this article.

Neurodevelopmental and Growth Outcomes of Extremely Preterm Infants with Short Bowel Syndrome.

OBJECTIVE: To determine if preterm infants with surgical necrotizing enterocolitis (sNEC) or spontaneous intestinal perforation (SIP) with short bowel syndrome (SBS) have worse neurodevelopmental and growth outcomes than those with sNEC/SIP without SBS, and those with no necrotizing enterocolitis, SIP, or SBS. STUDY DESIGN: We undertook a retrospective analysis of prospectively collected data from infants born between 22 and 26 weeks of gestation in the National Institute of Child Health and Human Development Neonatal Research Network centers from January 1, 2008, to December 31, 2016. Survivors were assessed at 18-26 months corrected age by standardized neurologic examination and Bayley Scales of Infant and Toddler Development, Third Edition. The primary outcome was moderate-severe neurodevelopmental impairment. Growth was assessed using World Health Organization z-score standards. Adjusted relative risks were estimated using modified Poisson regression models. RESULTS: Mortality was 32%, 45%, and 21% in the 3 groups, respectively. Eighty-nine percent of survivors were seen at 18-26 months corrected age. Moderate-severe neurodevelopmental impairment was present in 77% of children with SBS compared with 62% with sNEC/SIP without SBS (adjusted relative risk, 1.22; 95% CI, 1.02-1.45; P = .03) and 44% with no necrotizing enterocolitis, SIP, or SBS (adjusted relative risk, 1.60; 95% CI, 1.37-1.88; P < .001). Children with SBS had lowcognitive, language, and motor scores than children with sNEC/SIP without SBS. At follow-up, length and head circumference z-scores remained more than 1 SD below the mean for children with SBS. CONCLUSIONS: Preterm infants with sNEC/SIP and SBS had increased risk of adverse neurodevelopmental outcomes at 18-26 months corrected age and impaired growth compared with peers with sNEC/SIP without SBS or without any of these conditions.

Identification of novel HLA-restricted preferentially expressed antigen in melanoma peptides to facilitate off-the-shelf tumor-associated antigen-specific T-cell therapies.

BACKGROUND AIMS: Preferentially expressed antigen in melanoma (PRAME) is a cancer/testis antigen that is overexpressed in many human malignancies and poorly expressed or absent in healthy tissues, making it a good target for anti-cancer immunotherapy. Development of an effective off-the-shelf adoptive T-cell therapy for patients with relapsed or refractory solid tumors and hematological malignancies expressing PRAME antigen requires the identification of major histocompatibility complex (MHC) class I and II PRAME antigens recognized by the tumor-associated antigen (TAA) T-cell product. The authors therefore set out to extend the repertoire of HLA-restricted PRAME peptide epitopes beyond the few already characterized. METHODS: Peptide libraries of 125 overlapping 15-mer peptides spanning the entire PRAME protein sequence were used to identify HLA class I- and II-restricted epitopes. The authors also determined the HLA restriction of the identified epitopes. RESULTS: PRAME-specific T-cell products were successfully generated from peripheral blood mononuclear cells of 12 healthy donors. Ex vivo-expanded T cells were polyclonal, consisting of both CD4+ and CD8+ T cells, which elicited anti-tumor activity in vitro. Nine MHC class I-restricted PRAME epitopes were identified (seven novel and two previously described). The authors also characterized 16 individual 15-mer peptide sequences confirmed as CD4-restricted epitopes. CONCLUSIONS: TAA T cells derived from healthy donors recognize a broad range of CD4+ and CD8+ HLA-restricted PRAME epitopes, which could be used to select suitable donors for generating off-the-shelf TAA-specific T cells.

Management of Central Venous Access in Children With Intestinal Failure: A Position Paper From the NASPGHAN Intestinal Rehabilitation Special Interest Group.

ABSTRACT: Intestinal failure requires the placement and maintenance of a long-term central venous catheter for the provision of fluids and/or nutrients. Complications associated with this access contribute to significant morbidity and mortality, while the loss of access is an increasingly common reason for intestinal transplant referral. As more emphasis has been placed on the prevention of central line-associated bloodstream infections and new technologies have developed, care for central lines has improved; however, because care has evolved independently in local centers, care of central venous access varies significantly in this vulnerable population. The present position paper from the Intestinal Failure Special Interest Group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) reviews current evidence and provides recommendations for central line management in children with intestinal failure.

Approach to Intestinal Failure in Children.

PURPOSE OF REVIEW: Pediatric intestinal failure is a complex condition requiring specialized care to prevent potential complications. In this article, we review the available evidence supporting recent advances in care for children with intestinal failure. RECENT FINDINGS: Multidisciplinary intestinal rehabilitation teams utilize medical and surgical management techniques to help patients achieve enteral autonomy (EA) while preventing and treating the complications associated with intestinal failure. Recent advances in lipid management strategies, minimization of intestinal failure associated liver disease, prevention of central line-associated blood stream infections, and loss of access, as well as development of promising new hormone analogue therapy have allowed promotion of intestinal adaptation. These advances have decreased the need for intestinal transplant. There have been recent advances in the care of children with intestinal failure decreasing morbidity, mortality, and need for intestinal transplantation. The most promising new therapies involve replacement of enteroendocrine hormones.

[Pain management in sickle cell disease]. / Schmerztherapie bei Sichelzellkrankheit.

Sickle cell disease is associated with numerous symptoms and complications. Acute painful crisis is the most characteristic manifestation of the disease. In addition, many patients report chronic pain. As both acute and chronic pain severely diminish quality of life, adequate pain management is crucial. Recommendations for the treatment of acute painful crises are based on the World Health Organization analgesic ladder, which has been developed for cancer-related pain. Chronic pain can be treated with basic long-acting opioids and on-demand short-acting opioids. If patients show signs of neuropathic pain, administration of anticonvulsants, antidepressants or possibly ketamine should be considered.

[Pain management in osteoporosis]. / Schmerztherapie bei Osteoporose.

Osteoporosis is a very common disease all over the world, in which a reduction in bone density can lead to an increased risk of fractures and a diminished physical height. Osteoporosis is also associated with acute and chronic pain, which especially occurs in the back and can significantly reduce the quality of life. To provide sufficient care for affected patients, it is essential to know the particularities of pain management in osteoporosis, such as pharmacological and nonpharmacological treatment options. This article gives a comprehensive review of pain management in osteoporosis and also explains the underlying pathomechanisms, risk factors, and diagnostic procedures.

[Pain management in rare diseases]. / Schmerztherapie bei seltenen Erkrankungen.

In this article we address the relevance of rare diseases and their peculiarities with respect to pain therapy. Towards this end, four rare diseases (hemophilia, Morbus Fabry, dermatomyositis, and facioscapulohumeral dystrophy (FSHD)) will be presented and fundamental aspects of their pain therapies described. The diseases were chosen to showcase a pain therapy based on the WHO-step-by-step plan (hemophilia), a complex but established pain therapy (M. Fabry), and two less well established, individually adapted pain therapies (dermatomyositis, FSHD).

[Pain management in osteoporosis]. / Schmerztherapie bei Osteoporose.

Osteoporosis is a very common disease all over the world, in which a reduction in bone density can lead to an increased risk of fractures and a diminished physical height. Osteoporosis is also associated with acute and chronic pain, which especially occurs in the back and can significantly reduce the quality of life. To provide sufficient care for affected patients, it is essential to know the particularities of pain management in osteoporosis, such as pharmacological and nonpharmacological treatment options. This article gives a comprehensive review of pain management in osteoporosis and also explains the underlying pathomechanisms, risk factors, and diagnostic procedures.

Ultra-short bowel syndrome during infancy: improving outcomes and novel therapies.

PURPOSE OF REVIEW: Ultra-short bowel syndrome is relatively rare and has not yet been extensively reported. In ultra-short bowel syndrome, poor absorption of nutrients and dysmotility, interfere with fluid, energy, electrolyte and micronutrient balance. Patients with this disorder are managed through prolonged parenteral nutrition with the ultimate goal of achieving enteral autonomy. Overall outcomes of these patients are dependent on postsurgical bowel anatomy (residual length, intact colon, ostomy closure timing), incidence of sepsis, and care by a multidisciplinary specialized team. RECENT FINDINGS: Over the years, standardization of management has improved outcomes. This includes central line care, lipid alternatives, enteral therapy, medications (antidiarrheal agents, acid suppression medications, bile acid binding salts, and enteral antibiotics) including Teduglutide. Bowel lengthening procedures have also proven beneficial, and finally bowel transplant does remain an option for a patient in whom rehabilitation has failed. SUMMARY: Although there are many factors that influence outcomes of ultra-short bowel patients, novel therapies such as Teduglutide have been introduced with the aim of improving intestinal adaptation. Surgical lengthening and transplant are viable options in the setting of failed rehabilitation.

The Hadlock Method Is Superior to Newer Methods for the Prediction of the Birth Weight Percentile.

OBJECTIVES: To compare a traditional ultrasound (US) method for estimated fetal weight (EFW) calculation and fetal growth restriction diagnosis with 2 newer methods for the prediction of small for gestational age (SGA) at birth. METHODS: We reviewed deliveries at our institution from January 1, 2013, to March 31, 2017. Singleton, nonanomalous, well-dated fetuses with a US examination within 2 weeks of delivery were included. Estimated fetal weights and percentiles were calculated by a traditional method (Hadlock et al; Radiology 1991; 181:129-133) and 2 newer methods: Intergrowth-21st (INTG; Ultrasound Obstet Gynecol 2017; 49:478-486) and Salomon et al (Ultrasound Obstet Gynecol 2007; 29:550-555). We calculated each method's test characteristics to predict SGA (birth weight < 10th percentile) using both traditional (EFW < 10th percentile) and receiver operating characteristic (ROC)-derived fetal growth restriction cutoffs. Mean percentile discrepancies between EFW and birth weight measurements were calculated to compare method accuracy. We hypothesized that the INTG and Salomon methods would have superior SGA prediction compared with the Hadlock method. RESULTS: Of 831 pregnancies with a US examination within 2 weeks of delivery, 138 (16.7%) were SGA at birth. Hadlock had the smallest US-birth weight percentile discrepancy (P < .001 versus both INTG and Salomon). When comparing ROC curves, the Hadlock and INTG methods performed comparably, with areas under the curve of 0.91 and 0.90 (P = .08) and optimal EFW cutoffs of the 15th and 22nd percentiles, respectively. The Salomon method performed less well, with an area under the curve of 0.82 (P < .001 versus both Hadlock and INTG methods). CONCLUSIONS: In our study cohort, the Hadlock method predicted the birth weight percentile more accurately than the INTG or Salomon methods and performed comparably with INTG to predict SGA when ROC-derived cutoffs were used.

[Cannabis and cannabinoids-easier access, hype and disappointment : What has been confirmed in therapy?] / Cannabis und Cannabinoide ­ erleichterter Zugang, Hype und Enttäuschung : Was ist gesichert in der Therapie?

BACKGROUND: Cannabis products are being increasingly liberalized all over the world and there is a huge interest in cannabis-based medicine. OBJECTIVES: Presentation of current studies on the efficacy of different cannabis-based medicine for the treatment of various diseases CURRENT DATA: In German pharmaceutical legislation, nabiximols is approved for the treatment of moderate to severe therapy-resistant spasticity in multiple sclerosis and nabilone is approved for the treatment of therapy-resistant chemotherapy-associated nausea and vomiting. In case of therapy failure cannabinoids, as part of an individual therapeutic attempt, may be considered for the treatment of chronic pain (neuropathic pain, cancer pain, non-neuropathic noncancer pain), cachexia in human immunodeficiency virus as well as for Dravet and Lennox-Gastaut syndrome. From the authors' perspective there is not enough evidence for the use in chemotherapy-associated nausea and vomiting and chronic non-neuropathic pain. CONCLUSIONS: Currently, a wide use of cannabinoids does not seem probable in the near future. Further studies involving more patients and evaluating long-term effects are necessary.

ABOUND.2L+: A randomized phase 2 study of nanoparticle albumin-bound paclitaxel with or without CC-486 as second-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC).

BACKGROUND: This randomized phase 2 trial compared the efficacy and safety of second-line nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without the addition of CC-486 (an oral formulation of 5-azacytidine) in patients with advanced-stage, nonsquamous non-small cell lung cancer. METHODS: Patients were randomized to receive either nab-paclitaxel 100 mg/m2 on days 8 and 15 plus CC-486 200 mg daily on days 1 to 14 or single-agent nab-paclitaxel 100 mg/m2 on days 1 and 8, with both regimens administered every 21 days until tumor progression or unacceptable toxicity. The primary endpoint was progression-free survival. Secondary endpoints included the overall response rate, the disease control rate, and overall survival. RESULTS: Between January 2015 and August 2016, 161 patients were randomized (81 to the combination arm and 80 to the single-agent nab-paclitaxel arm). There was no benefit from the addition of CC-486 to nab-paclitaxel. The median progression-free survival was 3.2 months for the combination and 4.2 months for single-agent nab-paclitaxel (hazard ratio, 1.3; 95% confidence interval, 0.9-1.9). The median overall survival was 8.1 months in the combination arm and 17 months in the single-agent nab-paclitaxel arms (hazard ratio, 1.7; 95% confidence interval, 1.08-2.57). Grade 3 or greater treatment-related, emergent adverse events were reported by 40.5% of patients in the combination arm and by 31.6% of those in the single-agent nab-paclitaxel arm. CONCLUSIONS: Single-agent nab-paclitaxel was associated with promising outcomes and a tolerable safety profile as second-line treatment for patients with advanced-stage, nonsquamous non-small cell lung cancer. There was no benefit from the addition of CC-486 to nab-paclitaxel.

Comparing the Hadlock fetal growth standard to the Eunice Kennedy Shriver National Institute of Child Health and Human Development racial/ethnic standard for the prediction of neonatal morbidity and small for gestational age.

BACKGROUND: The fetal growth standard in widest use was published by Hadlock >25 years ago and was derived from a small, homogeneous cohort. In 2015, The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Study published updated standards that are specific to race/ethnicity. These do not allow for precise estimated fetal weight percentile calculation, however, and their effectiveness to predict neonatal morbidity and small for gestational age has not yet been compared to the long-standing Hadlock standard. OBJECTIVE: We compared the ability of the Hadlock standard to predict neonatal morbidity and small for gestational age at birth with that of The Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific standard. Our secondary objective was to compare their performance among our Native American population, which is not accounted for in the Eunice Kennedy Shriver National Institute of Child Health and Human Development standard. STUDY DESIGN: For this retrospective study of diagnostic accuracy, we reviewed deliveries at the University of New Mexico Hospital from Jan. 1, 2013, through March 31, 2017. We included mothers with singleton, well-dated pregnancies and nonanomalous fetuses with an estimated fetal weight within 30 days of delivery. Cubic spline interpolation was performed on the Eunice Kennedy Shriver National Institute of Child Health and Human Development estimated fetal weight-percentile tables to calculate percentiles specific to the gestational day. Estimated fetal weight percentiles were then calculated using both the Hadlock and Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific standards according to maternal self-identified race/ethnicity. We calculated the receiver operator area under the curve of each method to predict composite and severe composite neonatal morbidity and small for gestational age at birth (birthweight <10th percentile). As an additional measure of method accuracy, we calculated the mean ultrasound-birthweight percentile discrepancy. For Native Americans, percentiles were calculated using the Hadlock and Eunice Kennedy Shriver National Institute of Child Health and Human Development race/ethnicity standards (white, black, Hispanic, Asian), and test characteristics were calculated for each to predict neonatal morbidity and small for gestational age. RESULTS: We included 1514 women, with a mean ultrasonography-to-delivery interval of 14.4 days (±8.8) and a small for gestational age rate of 13.6% (n = 206). For the prediction of both composite and severe composite neonatal morbidity, the Hadlock method had superior performance, with higher areas under the curve than the Eunice Kennedy Shriver National Institute of Child Health and Human Development method (P < .001 for both), though neither had good discriminatory value (all areas under the curve <0.8). For the prediction of small for gestational age at birth, the Hadlock standard had higher sensitivity (61.1%) than the Eunice Kennedy Shriver National Institute of Child Health and Human Development standard, both when using the interpolated Eunice Kennedy Shriver National Institute of Child Health and Human Development method (36.2%, P < .01) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development whole-week 10th percentile cutoff (46.7%, P < .01). The Hadlock method also had a higher area under the curve than the Eunice Kennedy Shriver National Institute of Child Health and Human Development interpolated method to predict small for gestational age (0.89 vs 0.88, P < .01). The Hadlock method had a lower ultrasound-birthweight percentile discrepancy than the Eunice Kennedy Shriver National Institute of Child Health and Human Development method (6.1 vs 16.5 percentile points, P < .01). Fetuses classified as growth restricted by Hadlock but not Eunice Kennedy Shriver National Institute of Child Health and Human Development had significantly higher composite morbidity than normally grown fetuses. Among Native American women, the Hadlock method had the highest area under the curve to predict composite and severe composite morbidity, while the Hadlock and all Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific methods performed comparably to predict small for gestational age. CONCLUSION: Despite its publication >25 years ago, the Hadlock standard is superior to the Eunice Kennedy Shriver National Institute of Child Health and Human Development race-/ethnicity-specific standard for the prediction of both neonatal morbidity and small for gestational age.

Cantharidin is Superior to Trichloroacetic Acid for the Treatment of Non-mucosal Genital Warts: A Pilot Randomized Controlled Trial.

Condyloma Acuminatum is a sexually transmitted viral disease caused by the human papilloma virus (HPV). It is the most common viral sexually transmitted disease. In this randomized controlled trial, cantharidin was found to be more effective and better tolerated than trichloroacetic acid for the treatment of these lesions. Patients treated with cantharidin healed with less scarring than those treated with TCA (P<0.034), had less pain during treatment (P<0.01), and required fewer treatments to eradicate warts (P<0.01) when compared to Trichloroacetic acid.