Lost dwell time and cycler alarms in inpatient automated peritoneal dialysis at a tertiary care hospital.

BACKGROUND AND AIMS: Dwell time is a critical component of automated peritoneal dialysis (APD) prescription, the stage at which transmembrane mass and fluid transfer occur. Loss of prescribed dwell time (LDT) can negatively influence the efficiency of APD. We investigated the incidence of LDT and related causes using APD in the acute care setting at a tertiary care center. METHODS: Retrospective analysis was conducted of all inpatients receiving APD treatments from 1 December 2021 to 1 June 2023. Patient demographics, comorbidities, laboratory, and treatment data were extracted from electronic medical records and a propriety database. RESULTS: N = 235 cycler treatments completed by 32 patients were included for analysis. The total LDT per treatment exceeding 30 minutes and 60 minutes occurred in 27% and 20% of all treatments. LDT of more than 10 minutes per each cycle exchange occurred in 26%. Session disruptions were caused by slow out-flow (55%), inadequate drain volumes (32%), patient line occlusions (20%), and priming errors (23%). The slow flow alarm requiring user intervention was reported to occur in about one-third of all treatments (31%). CONCLUSION: There was significant LDT and inadequate drain volume seen in about one-quarter and one-third of all inpatient APD treatments respectively. This can impact solute clearance and ultrafiltration.  Slow flow alarms were the most prevalent and the leading cause of LDT followed by inadequate drain volume. Future studies are required to investigate measures to reduce slow drain and improve drain volume in the hospital setting.   .

Representation of women in clinical trials supporting FDA-approval of contemporary cancer therapies.

Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.

Comparison of atrial fibrillation prevalence and in-hospital cardiovascular outcomes between patients undergoing allogeneic versus autologous hematopoietic stem cell transplantation: insights from the national inpatient sample.

Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for several malignant and non-malignant hematologic conditions. However, patients undergoing HSCT are at increased risk of developing serious cardiovascular events. Whether cardiovascular risks differ by the type of transplantation strategy used, allogeneic versus autologous HSCT, is unknown. Leveraging the National Inpatient Sample (2016-2019), we assessed the incidence of early cardiovascular events by HSCT mode (allogeneic vs autologous). The primary outcome was the incidence of atrial fibrillation (AF). The secondary outcome was the occurrence of any major adverse cardiac events (MACE), defined as acute heart failure, myocardial infarction (MI), symptomatic atrial or ventricular arrhythmia or heart block, and cardiovascular death. Outcomes were compared between those undergoing allogeneic versus autologous HSCT. Multivariable regression, adjusting for cardiovascular and cancer-related factors, was used to define the association between pre-HSCT factors and MACE. We further assessed the effect of acute cardiovascular events on in-patient mortality by calculating adjusted odds ratio (aOR) with corresponding 95% confidence intervals (CI) and p-values. Overall, 64,705 weighted hospitalizations for HSCT were identified, of which 22,655 (35.0%) were allogeneic HSCT and 42,050 (65.0%) were autologous HSCT. The prevalence of AF was 9.1%, and 12.1% for any arrhythmia. In multivariable regression, allogeneic HSCT was associated with higher adjusted odds of peri-HSCT acute heart failure (aOR 2.64; 1.86-3.76; p < 0.0001), QT prolongation (aOR 1.40; 1.04-1.88; p = 0.025), MI (aOR 2.87; 1.16-7.11; p = 0.023), any major cardiovascular complication (aOR 1.16; 1.03-1.32; p = 0.016), and inpatient mortality (aOR 4.87; 3.60-6.58; p < 0.0001). Following cerebrovascular events, AF was the strongest predictor of mortality. Allogeneic HSCT was associated with higher odds of in-hospital cardiovascular complications among patients undergoing HSCT.

Niraparib Maintenance Therapy for Brain Metastasis in Ovarian Endometrioid Adenocarcinoma With Peritoneal Carcinomatosis: A Comprehensive Case Study and Literature Review.

Brain metastasis is a rare complication of ovarian cancer, always found at the advanced stage. Even though different multimodal approaches are available, including surgical intervention and radiotherapy, there are no official guidelines for handling this serious complication. Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are a group of medications initially used for maintenance therapy in platinum-sensitive recurrent ovarian cancer. Niraparib has shown some efficacy in patients with brain metastasis due to its unique properties of penetrating the blood-brain barrier. Here, we present the case of a 51-year-old patient with advanced ovarian cancer with no germline breast cancer susceptibility gene (BRCA) mutations. Despite undergoing surgery and multiple rounds of chemotherapy, the patient's condition worsened, culminating in brain metastasis. Given her neurological issues, radiotherapy was not an option, prompting the initiation of a 300 mg dose of niraparib. To date, only sporadic case reports in the literature have described patients with ovarian cancer treated with niraparib and complicated by brain metastasis. Our case is unique because it is the first case of a patient with the endometrioid type of ovarian cancer.

Clinical management of unremitting nephrogenic diabetes insipidus.

The polyuria and polydipsia state in diabetes insipidus (DI) can be challenging to manage for patients and clinicians with significant impact on the patients' well-being. A review of literature shows that nonsteroidal anti-inflammatory drugs (NSAIDs), thiazide and potassium-sparing diuretics, along with low dietary solute and protein, and high water intake remain the standard medical therapy. Although these therapeutic approaches improve symptoms, the urine-concentrating defect is still considerable, posing a serious risk to patient's life from hypovolemia if high fluid intake is not maintained. Our case describes the challenges faced with the medical management of a patient with nephrogenic DI that was only partially responsive to standard medical therapy, resulting in debilitating effects on the patient's quality of life.

Green synthesized silver nanoparticles from Phoenix dactylifera synergistically interact with bioactive extract of Punica granatum against bacterial virulence and biofilm development.

The global rise of antibiotic resistance poses a substantial risk to mankind, underscoring the necessity for alternative antimicrobial options. Developing novel drugs has become challenging in matching the pace at which microbial resistance is evolving. Recently, nanotechnology, coupled with natural compounds, has emerged as a promising solution to combat multidrug-resistant bacteria. In the present study, silver nanoparticles were green-synthesized using aqueous extract of Phoenix dactylifera (variety Ajwa) fruits and characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) coupled with Energy dispersive X-ray analysis (EDX), Transmission electron microscopy (TEM) and Thermogravimetric-differential thermal analysis (TGA-DTA). The in-vitro synergy of green synthesized P. dactylifera silver nanoparticle (PD-AgNPs) with selected antibiotics and bioactive extract of Punica granatum, i.e., ethyl acetate fraction (PGEF), was investigated using checkerboard assays. The most effective synergistic combination was evaluated against the QS-regulated virulence factors production and biofilm of Pseudomonas aeruginosa PAO1 by spectroscopic assays and electron microscopy. In-vivo anti-infective efficacy was examined in Caenorhabditis elegans N2 worms. PD-AgNPs were characterized as spherical in shape with an average diameter of 28.9 nm. FTIR analysis revealed the presence of functional groups responsible for the decrease and stabilization of PD-AgNPs. The signals produced by TGA-DTA analysis indicated the generation of thermally stable and pure crystallite AgNPs. Key phytocompounds detected in bioactive fractions include gulonic acid, dihydrocaffeic acid 3-O-glucuronide, and various fatty acids. The MIC of PD-AgNPs and PGEF ranged from 32 to 128 µg/mL and 250-500 µg/mL, respectively, against test bacterial strains. In-vitro, PD-AgNPs showed additive interaction with selected antibiotics (FICI 0.625-0.75) and synergy with PGEF (FICI 0.25-0.375). This combination inhibited virulence factors by up to 75 % and biofilm formation by 84.87 % in P. aeruginosa PAO1. Infected C. elegans worms with P. aeruginosa PAO1 had a 92.55 % survival rate when treated with PD-AgNPs and PGEF. The combination also reduced the reactive oxygen species (ROS) level in C. elegans N2 compared to the untreated control. Overall, these findings highlight that biosynthesized PD-AgNPs and bioactive P. granatum extract may be used as a potential therapeutic formulation against MDR bacteria.

Telehealth cognitive behaviour therapy for the management of sleep disturbance in women with early breast cancer receiving chemotherapy: a feasibility study.

PURPOSE: Sleep quality commonly deteriorates in people receiving chemotherapy for breast cancer (BC). We aimed to determine feasibility and acceptability of telehealth-delivered cognitive behaviour therapy for insomnia (CBT-I) in people with early BC receiving (neo)adjuvant chemotherapy. METHODS: Multi-centre, single arm, phase 2 feasibility trial. People with stage I-III BC received 4 sessions of telehealth CBT-I over 8 weeks, during chemotherapy. Participants completed Pittsburgh Sleep Quality Index (PSQI) and other Patient Reported Outcome Measures (PROMs) at baseline, post-program (week 9) and post-chemotherapy (week 24); and an Acceptability Questionnaire at week 9. Primary endpoint was proportion completing 4 sessions of telehealth CBT-I. RESULTS: In total, 41 participants were recruited: mean age 51 years (range 31-73). All 4 CBT-I sessions were completed by 35 (85%) participants. Acceptability of the program was high and 71% reported 'the program was useful'. There was no significant difference in the number of poor sleepers (PSQI score ≥ 5) at baseline 29/40 (73%) and week 24 17/25 (68%); or in the mean PSQI score at baseline (7.43, SD 4.06) and week 24 (7.48, SD 4.41). From baseline to week 24, 7/25 (28%) participants had a ≥ 3 point improvement in sleep quality on PSQI, and 5/25 (20%) had a ≥ 3 point deterioration. There was no significant difference in mean PROM scores. CONCLUSION: It is feasible to deliver telehealth CBT-I to people with early BC receiving chemotherapy. Contrary to literature predictions, sleep quality did not deteriorate. Telehealth CBT-I has a potential role in preventing and managing sleep disturbance during chemotherapy. Australian New Zealand Clinical Trials Registry (ANZCTR) registration number: ACTRN12620001379909 and date 22/12/2020.

Hepatitis C viremic lung transplantation to aviremic recipients: Comprehensive outcomes and post-transplant viremia.

BACKGROUND/AIMS: Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). METHODS: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. RESULTS: We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p = .43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p = .89, p = .87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p = .90, p = .88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p = .3), acute cellular rejection (60.0% vs. 58.0%, p = .8) and antibody-mediated rejection (16.7% vs. 14.2%, p = .7). CONCLUSION: There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.

Attitude and Behavior of Parents of Children With Sickle Cell Disease Toward the Disease: An Observational Study in Saudi Arabia.

BACKGROUND: Sickle cell disease (SCD) is a significant hematological disorder affecting populations worldwide, with a notable prevalence in certain regions of Saudi Arabia. Despite extensive screening programs, there is a critical need for improved public health education to enhance understanding and management of SCD. This study examines the relationship between the attitudes and behaviors of parents toward their children's disease and its management. METHODS: We conducted a cross-sectional observational study at the King Fahd Medical Research Center in Jeddah. This research encompassed children aged 5-16 years with SCD and their parents. Comprehensive questionnaires assessed sociodemographic data, attitudes toward SCD, and behavioral responses to the illness and treatment. RESULTS: The study included 66 parents, predominantly in the age range of 30-39 years and earning below 5000 Saudi Riyals, who exhibited varying attitudes towards SCD, with a majority questioning the availability of a cure and expressing caution towards new treatments. Despite a cautious approach to invasive treatments, parents relied on information from healthcare providers. Attitudes towards treatment showed significant differences based on gender and education level, with females and less-educated parents exhibiting more hesitancy towards new treatment and blood transfusions. CONCLUSION: The study indicates that while parents show a positive and proactive attitude toward SCD, there is hesitancy towards new and invasive treatments, reflecting the need for continued educational support. The results underscore the importance of tailored healthcare communication strategies to address the diverse needs of families affected by SCD.

Comparison of fungal vs bacterial infections in the medical intensive liver unit: Cause or corollary for high mortality?

BACKGROUND: Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure. AIM: To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections. METHODS: From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review. RESULTS: All fungal infections were due to Candida species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% vs 52%, P < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% vs 64%, P = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% vs 70%, P = 0.04), mechanical ventilation (96% vs 65%, P < 0.001), and dialysis due to acute kidney injury (78% vs 52%, P = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 vs 91, P = 0.003), Acute Physiology Score (86 vs 65, P = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 vs 65, P = 0.041). There was no significant difference in the rate of central line use preceding culture (52% vs 40%, P = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance. CONCLUSION: Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.

Giredestrant for Estrogen Receptor-Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study.

PURPOSE: To compare giredestrant and physician's choice of endocrine monotherapy (PCET) for estrogen receptor-positive, HER2-negative, advanced breast cancer (BC) in the phase II acelERA BC study (ClinicalTrials.gov identifier: NCT04576455). METHODS: Post-/pre-/perimenopausal women, or men, age 18 years or older with measurable disease/evaluable bone lesions, whose disease progressed after 1-2 lines of systemic therapy (≤1 targeted, ≤1 chemotherapy regimen, prior fulvestrant allowed) were randomly assigned 1:1 to giredestrant (30 mg oral once daily) or fulvestrant/aromatase inhibitor per local guidelines (+luteinizing hormone-releasing hormone agonist in pre-/perimenopausal women, and men) until disease progression/unacceptable toxicity. Stratification was by visceral versus nonvisceral disease, prior cyclin-dependent kinase 4/6 inhibitor, and prior fulvestrant. The primary end point was investigator-assessed progression-free survival (INV-PFS). RESULTS: At clinical cutoff (February 18, 2022; median follow-up: 7.9 months; N = 303), the INV-PFS hazard ratio (HR) was 0.81 (95% CI, 0.60 to 1.10; P = .1757). In the prespecified secondary end point analysis of INV-PFS by ESR1 mutation (m) status in circulating tumor DNA-evaluable patients (n = 232), the HR in patients with a detectable ESR1m (n = 90) was 0.60 (95% CI, 0.35 to 1.03) versus 0.88 (95% CI, 0.54 to 1.42) in patients with no ESR1m detected (n = 142). Related grade 3-4 adverse events (AEs), serious AEs, and discontinuations due to AEs were balanced across arms. CONCLUSION: Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.

Cardiovascular toxicities associated with bispecific T-cell engager therapy.

BACKGROUND: Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs. METHODS: Leveraging the US Food and Drug Administration's Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated. RESULTS: From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome. CONCLUSION: In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk.

Are We the Problem? A Call to Action for Addressing Institutional Challenges to Engaging Community Partners in Research.

Community-engaged research (CEnR) is a potent tool for addressing health inequities and fostering equitable relationships among communities, researchers, and institutions. CEnR involves collaboration throughout the research process, demonstrating improvements in study recruitment and retention, intervention efficacy, program sustainability, capacity building among partners, and enhanced cultural relevance. Despite the increasing demand for CEnR, institutional policies, particularly human participation protection training (HPP), lag behind, creating institutional barriers to community partnerships. Here, we highlight challenges encountered in our ongoing study, Fostering Opportunities in Research through Messaging and Education (FOR ME), focused on promoting shared decision-making around clinical trial participation among Black women diagnosed with breast cancer. Grounded in CEnR methods, FOR ME has a partnership with a community-based organization (CBO) that addresses the needs of Black women with breast cancer. Our CBO partner attempted to obtain HPP training, which was administratively burdensome and time-consuming. As CEnR becomes more prevalent, academic and research institutions, along with researchers, are faced with a call to action to become more responsive to community partner needs. Accordingly, we present a guide to HPP training for community partners, addressing institutional barriers to community partner participation in research. This guide outlines multiple HPP training pathways for community partners, aiming to minimize institutional barriers and enhance their engagement in research with academic partners.

Gender and its association with cardiac defects in down syndrome population at Children Hospital & Institute of Child Health, Lahore, Pakistan.

Objective: The objective of this study was to determine the frequency of different congenital cardiac defects co-existing in karyotypically proved Down syndrome population. It also highlighted the association between gender and pattern of congenital cardiac defects and gender as a risk factor. Methods: A cross sectional comparative study was done in the Department of Genetics, Children Hospital Lahore in the year 2017. A total of 160 patients were subjected to karyotypic analysis through blood test for determining the type of Down Syndrome and Echocardiography of all established cases was performed for determining presence and types of congenital cardiac defects. Results were evaluated in terms of establishing co-existence of various cardiac phenotypes in Down Syndrome cases. Results: In karyotypically proven 160 cases of Down syndrome, 58.1% of Down Syndrome cases and 88.2% of Down Syndrome with Congenital Cardiac Defects presented in infancy. The odds ratio (OR) suggested that females are 1.72 times more likely to experience a cardiac effect compared to males. Female gender was potentially associated (p-value 0.07) with occurrence of Patent Ductus Arteriosus (47.8%), whereas VSD (Ventricular Septal Defects) was most prevalent (41.1%) in males. Patent Ductus Arteriosus + Atrial Septal Defects (44.4%) was the commonest cardiac defect in female cases. The combined data for pattern of cardiac anomalies showed no significant association with gender, as indicated by a p-value of 0.990. Conclusion: The study concluded that most of Down syndrome cases and Down syndrome with congenital cardiac defects present to the hospital in infancy. Female cases are more prone to develop cardiac defects as compared to males. The manifestation of PDA (Patent Ductus Arteriosus) was significantly associated as an isolated anomaly in females and VSD (Ventricular Septal Defects) as isolated anomaly in males. Patent Ductus Arteriosus tend to co-exist most with ASD (Atrial Septal Defects) in female cases. Gender was not established as a risk factor for affecting the pattern of cardiac defects.

A Rare Case of Primary Malignant Melanoma of Cervical Spine Having Extramedullary Intradural Origin: A Single Case Report and Literature Review.

Introduction: Primary spinal malignant melanoma (PSMM) of extramedullary intradural origin is a rare malignant condition with limited current literature regarding its clinical course, magnetic resonance imaging (MRI) findings, treatment strategies, and outcomes. Case Discussion: This is a case report of a patient with PSMM who was treated with surgery followed by radiotherapy for his residual disease in Shaukat Khanum Memorial Trust, Pakistan. The clinical and radiological findings of this case were retrospectively analyzed using the Hospital Information System. Practical implementations: PSMM of extramedullary intradural origin is a rare malignant tumor that shows characteristic findings on MRI. Surgical resection is the preferred treatment, and radiotherapy is useful for residual disease.

Association of cerebrospinal fluid parameters with treatment and complications among children with cerebrospinal fluid shunt infections: a multicenter study.

OBJECTIVE: Cerebrospinal fluid (CSF) white blood cell (WBC) count, neutrophil percentage, protein concentration, and glucose level are typically measured at diagnosis and serially during the treatment of CSF shunt infections. The objective of this retrospective cohort study was to describe the longitudinal profile of CSF parameters in children with CSF shunt infections and assess their association with treatment and outcome. METHODS: Participants were children treated at 11 tertiary pediatric hospitals in Canada and the United States for CSF shunt infection, from July 1, 2013, through June 30, 2019, with hardware removal, external ventricular drain placement, intravenous antibiotics, and subsequent permanent shunt reinsertion. The relationship between CSF parameters and a complicated course (a composite outcome representing children with at least one of the following: contiguous soft-tissue infection, worsening hydrocephalus, CSF leak, intracranial bleed, brain abscess, venous thrombosis, reinfection after insertion of the new shunt, other complication, ICU admission, or death) was analyzed. RESULTS: A total of 109 children (median age 2.8 years, 44% female) were included in this study. CSF pleocytosis, elevated protein, and hypoglycorrhachia had sensitivities of 69%, 47%, and 38% for the diagnosis of culture-confirmed CSF shunt infection, respectively. The longitudinal profile of the neutrophil percentage followed a monotonic trend, decreasing by 1.5% (95% CI 1.0%-2.0%, p < 0.0001) per day over the course of treatment. The initial WBC count differed significantly between pathogens (p = 0.011), but the proportion of neutrophils, protein concentration, and glucose level did not, and was lowest with Cutibacterium acnes. The duration of antibiotic treatment and the time to shunt reinsertion were longer in patients with a higher initial neutrophil percentage. Fifty-eight patients (53%) had one or more complications during their admission. A neutrophil percentage > 44% (Youden index) in the initial CSF sample was associated with a 1.8-fold (95% CI 1.2- to 2.8-fold) higher relative risk of a complicated course. In a random-intercept, random-slope linear mixed-effects model, the longitudinal neutrophil trajectory differed significantly between patients with and without complications (p = 0.030). CONCLUSIONS: A higher proportion of neutrophils in the CSF at diagnosis was associated with a complicated clinical course. Other CSF parameters were associated with treatment and outcome; however, wide variability in values may limit their clinical utility.

Proposed diagnostic criteria for the diagnosis of hypophosphatasia in children and adolescents: results from the HPP International Working Group.

Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL gene, resulting in low activity of tissue nonspecific alkaline phosphatase (TNSALP). Patients with HPP tend have a similar pattern of elevation of natural substrates that can be used to aid in diagnosis. No formal diagnostic guidelines currently exist for the diagnosis of this condition in children, adolescents, or adults. The International HPP Working Group is a comprised of a multidisciplinary team of experts from Europe and North America who have expertise in the diagnosis and management of patients with HPP. This group reviewed 93 papers through a Medline, Medline In-Process, and Embase search for the terms "HPP" and "hypophosphatasia" between 2005 and 2020 and that explicitly address either the diagnosis of HPP in children, clinical manifestations of HPP in children, or both. Two reviewers independently evaluated each full-text publication for eligibility and studies were included if they were narrative reviews or case series/reports that concerned diagnosis of pediatric HPP or included clinical aspects of patients diagnosed with HPP. This review focused on 15 initial clinical manifestations that were selected by a group of clinical experts.The highest agreement in included literature was for pathogenic or likely pathogenic ALPL variant, elevation of natural substrates, and early loss of primary teeth. The highest prevalence was similar, including these same three parameters and including decreased bone mineral density. Additional parameters had less agreement and were less prevalent. These were organized into three major and six minor criteria, with diagnosis of HPP being made when two major or one major and two minor criteria are present.