Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update.

PURPOSE: To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients. METHODS: The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered. RESULTS: We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients. CONCLUSION: The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care.

A Rare De Novo Myoepithelial Carcinoma Ex Pleomorphic Adenoma in a Young Woman.

Carcinoma ex pleomorphic adenoma, an uncommon neoplasm of the parotid gland, accounts for less than 4% of salivary gland tumors. It arises from a benign pleomorphic adenoma presenting in the sixth to eighth decades of life. We present this as a unique account of a primary parotid gland carcinoma, arising from myoepithelial cells, without a known precursor lesion, in a 28-year-old woman. This presentation seeks to provide familiarity of an unusual presentation of an unexpected rare pathology in a young female patient and the tools utilized for an accurate diagnosis.

Guideline for Antibacterial Prophylaxis Administration in Pediatric Cancer and Hematopoietic Stem Cell Transplantation.

BACKGROUND: Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Systemic antibacterial prophylaxis is one approach that can be used to reduce the risk of these infections. Our purpose was to develop a clinical practice guideline (CPG) for systemic antibacterial prophylaxis administration in pediatric patients with cancer and those undergoing HSCT. METHODS: An international and multidisciplinary panel was convened with representation from pediatric hematology/oncology and HSCT, pediatric infectious diseases (including antibiotic stewardship), nursing, pharmacy, a patient advocate, and a CPG methodologist. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to generate recommendations based on the results of a systematic review of the literature. RESULTS: The systematic review identified 114 eligible randomized trials of antibiotic prophylaxis. The panel made a weak recommendation for systemic antibacterial prophylaxis for children receiving intensive chemotherapy for acute myeloid leukemia and relapsed acute lymphoblastic leukemia (ALL). Weak recommendations against the routine use of systemic antibacterial prophylaxis were made for children undergoing induction chemotherapy for ALL, autologous HSCT and allogeneic HSCT. A strong recommendation against its routine use was made for children whose therapy is not expected to result in prolonged severe neutropenia. If used, prophylaxis with levofloxacin was recommended during severe neutropenia. CONCLUSIONS: We present a CPG for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. Future research should evaluate the long-term effectiveness and adverse effects of prophylaxis.

Cost-effective teaching of radiology with preclinical anatomy.

Graduating physicians in all subspecialties have an increased need for competency in radiology, particularly since the use of diagnostic imaging continues to grow. To integrate the teaching of radiology with anatomy during the first year of medical school at Howard University, a novel approach was developed to overcome the limitations of resources including funding, faculty, and curricular time. The resulting program relies on self-study and peer-to-peer interactions to develop proficiency at manipulating free versions of medical image viewer software (using the DICOM standard), identifying normal anatomy in medical images, and applying critical thinking skills to understand common clinical conditions. An effective collaborative relationship between a radiologist and anatomist was necessary to develop and implement the program of anatomic-radiographic instruction which consists of five tiers: (1) initial exposure to anatomy through dissection which provides a foundation of knowledge; (2) study of annotated radiographs from atlases; (3) a radiology quiz open to group discussions; (4) small group study of clinical cases with diagnostic images; and (5) radiographic tests. Students took all quizzes and tests by working from image datasets preloaded on their personal computers, mimicking the approach by which radiologists analyze medical images. In addition to stimulating student support of a new teaching initiative, the strengths of Howard's program are that it can be introduced into an existing preclinical curriculum in almost any medical school with minimal disruption, it requires few additional resources to implement and run, and its design is consistent with the principles of modern education theory. Anat Sci Educ 11: 196-206. © 2017 American Association of Anatomists.

Laparoscopic Repair of Diaphragmatic Rupture: A Case Report with Radiological and Surgical Correlation.

The leading cause of diaphragmatic rupture is penetrating abdominal trauma, including gunshot- and stab-related wounds; however, diaphragmatic rupture can also result from blunt trauma to the abdomen. The diagnosis can be difficult to make as the physical examination may be unremarkable, and imaging, that is, a conventional chest X-ray and/or CT imaging, may initially fail to reveal the injury. Failure to recognize diaphragmatic rupture can result in a delayed presentation, sometimes years later, with a potential catastrophic outcome. Therefore, prompt and swift diagnosis is critical to avoid this potential harmful scenario. Traditionally, repair is performed through a laparotomy or a thoracotomy incision. Owing to the many advances made in minimally invasive surgery, not only has laparoscopy become the modality of choice to diagnose diaphragmatic rupture due to its high degree of sensitivity and specificity, but it can provide simultaneous therapeutic intervention as well. We report a case of laparoscopic repair of a diaphragmatic rupture in a 22-year-old female who sustained blunt abdominal trauma during a motor vehicle accident.

Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update.

Purpose To update a clinical practice guideline (CPG) for the empirical management of fever and neutropenia (FN) in children with cancer and hematopoietic stem-cell transplantation recipients. Methods The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group of experts in pediatric oncology and infectious diseases that includes a patient advocate. For questions of risk stratification and evaluation, we updated systematic reviews of observational studies. For questions of therapy, we conducted a systematic review of randomized trials of any intervention applied for the empirical management of pediatric FN. The Grading of Recommendation Assessment, Development and Evaluation approach was used to make strong or weak recommendations and to classify levels of evidence as high, moderate, low, or very low. Results Recommendations related to initial presentation, ongoing management, and empirical antifungal therapy of pediatric FN were reviewed; the most substantial changes were related to empirical antifungal therapy. Key differences from our 2012 FN CPG included the listing of a fourth-generation cephalosporin for empirical therapy in high-risk FN, refinement of risk stratification to define patients with high-risk invasive fungal disease (IFD), changes in recommended biomarkers and radiologic investigations for the evaluation of IFD in prolonged FN, and a weak recommendation to withhold empirical antifungal therapy in IFD low-risk patients with prolonged FN. Conclusion Changes to the updated FN CPG recommendations will likely influence the care of pediatric patients with cancer and those undergoing hematopoietic stem-cell transplantation. Future work should focus on closing research gaps and on identifying ways to facilitate implementation and adaptation.

Effect of concomitant use of memantine on mortality and efficacy outcomes of galantamine-treated patients with Alzheimer's disease: post-hoc analysis of a randomized placebo-controlled study.

BACKGROUND: A large, prospective, 2-year, randomized study in patients with mild-to-moderate Alzheimer's disease or mixed dementia demonstrated reductions in mortality and cognitive/functional decline in galantamine-treated patients. A post-hoc analysis was conducted to study the effect of (the presence or absence of) concomitant memantine use on treatment outcome. METHODS: Randomized patients (N = 2045) were divided into subgroups based on memantine use. Analyses included demographic and clinical characteristics (age, nursing home placement, Mini-Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD) scores) and mortality endpoints. RESULTS: Overall, 496 (24.3 %) patients were memantine users and were older (mean (SD), 74.0 (8.76) vs 72.8 (8.76), p = 0.008), with lower MMSE scores (18.2 (4.16) vs 19.2 (4.02), p < 0.0001) and DAD scores (58.0 (23.49) vs 62.5 (20.52), p < 0.0001) than nonusers. Mortality rates (per 100 patient-years) in memantine nonusers (n = 1549) were lower for galantamine (1.39) vs placebo-treated patients (4.15). In memantine users, mortality rates were similar for placebo-treated (4.49) and galantamine-treated patients (5.57). In memantine nonusers at 24 months, the decline in MMSE scores (effect size (95 % CI) 0.25 (0.14; 0.36)) and DAD scores (0.17 (0.06; 0.28)) from baseline was lower in galantamine patients vs placebo patients. The absence of these benefits in memantine users could not be explained by baseline age, MMSE, or DAD scores. CONCLUSION: This post-hoc analysis shows that the beneficial effects of galantamine at 2 years post treatment were not observed in patients who had been placed on background memantine. The reasons for memantine treatment and the possibility of interaction between memantine and galantamine merit further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00679627 . Registered 15 May 2008.

Ossification of the Posterior Longitudinal Ligament: Imaging Findings in the Era of Cross-Sectional Imaging.

Imaging appearance and classification systems of ossification of the posterior longitudinal ligament (OPLL) on computed tomography and magnetic resonance imaging will be reviewed. Computed tomography evaluation most accurately demonstrates OPLL length and thickness, whereas magnetic resonance imaging has the advantage of demonstrating abnormal signal in the cord. Neurologic symptoms are most common in the cervical spine and are related to the degree of spinal stenosis and presence of cord edema. Surgical treatment usually involves cases of cervical OPLL and includes anterior or posterior decompression.

Renal malakoplakia mimicking a malignant renal carcinoma: a patient case with literature review.

Malakoplakia, a medical, surgical, pathological and radiological enigma, is an infrequent chronic inflammatory condition that can affect many organ systems, including the gastrointestinal tract, integument, skeletal system and genitourinary tract. Review of the literature has shown that malakoplakia presents in paediatric as well as adult populations, and that it is associated with impaired immune function. Variable clinical manifestations as well as the sometimes non-specific radiological findings of malakoplakia can be misleading, making diagnosis quite difficult. We present a clinical case of renal malakoplakia mimicking a malignant renal carcinoma in a 62-year-old woman. This report highlights the importance of awareness of malakoplakia in the differential diagnosis for renal masses and renomegaly. This case can serve as a reminder that things are not always what they seem, and it reinforces the idea that unusual disease entities should be explored to aid in achieving a correct diagnosis and, thus, potentially avoid unnecessary treatment.

Assessing the value of routine upper gastrointestinal contrast studies following bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: Understanding both the efficacy of upper gastrointestinal (UGI) contrast studies and the factors that impact their accuracy is necessary to optimize postoperative imaging protocols. However, a consensus as to the value of UGI performed after bariatric surgery remains elusive. The objective was to determine the sensitivity and specificity of UGI conducted routinely within 2 days after bariatric surgery for detecting anastomotic leaks. METHODS: We conducted an electronic search of MEDLINE for all English language articles published between 2003 and 2013 concerning diagnostic imaging after bariatric surgery. Nineteen studies evaluating a total of 10,139 patients met the inclusion criteria. The methodological quality of each included study was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 procedure. RESULTS: UGI has an overall sensitivity of .54 and a specificity of 1.00. The standard deviation of the reported sensitivities was .36. Positive and negative predictive values were .67 and .98, respectively. Sensitivity and specificity were negatively correlated. CONCLUSIONS: The sensitivity of UGI for detecting the presence of anastomotic leaks within 2 days of bariatric surgery is moderate overall but fluctuates substantially. The negative correlation between sensitivity and specificity could indicate that the threshold used to distinguish between positive and negative test results varies between institutions. Accordingly, clinicians may consider shifting the threshold for declaring a UGI positive; treating marginal radiological evidence of leakage as presumptively positive may be a simple way to lower specificity, increase sensitivity, and in turn maximize UGI's clinical value.

Complication of Invasive Molar Pregnancy with Clostridium perfringens Sepsis.

Clostridium perfringens (CP) is an anaerobic, Gram-positive bacillus associated with malignant diseases and near-term pregnancies. The necrotic tissue that results from these disease processes fuels the proliferation of CP, leading to gas gangrene and subsequently sepsis. Herein, we report a case of a 41-year-old female patient with a history of invasive molar pregnancy that was further complicated with a CP infection. Although past research has shown a link between Clostridium infection and choriocarcinoma (Chern-Horng and Hsieh, 1999), no previous cases of CP infection have been associated with invasive molar pregnancy. We also report complete resolution of the CP sepsis and its associated symptoms following the hysterectomy.

Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease.

BACKGROUND: Currently available treatments for Alzheimer's disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD. METHODS: In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the 'last observation carried forward' approach, in an analysis of covariance model. RESULTS: In all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (-2.14 [4.34]) compared with the galantamine group (-1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (-10.81 [18.27]) versus the galantamine group (-8.16 [17.25]) (P=0.002). Incidences of treatment-emergent adverse events were 54.0% for the galantamine and 48.6% for the placebo group. CONCLUSION: Long-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients. IDENTIFICATION: This study is registered at ClinicalTrials.gov (NCT00679627).

Curative treatment of esophageal cancer; an evidenced based review.

BACKGROUND: In 2013, roughly 18,000 cases of esophageal cancer will be diagnosed in the United States with more than 15,000 people dying from the disease. Worldwide, an estimated 482,300 new esophageal cancer cases were diagnosed with 406,800 deaths in 2008. Squamous cell carcinoma (SCC) and adenocarcinoma (AC) account for >90% of all esophageal cancer cases. METHODS: The authors will examine the role of radiation therapy, chemotherapy, and surgery in the curative management of esophageal cancer by examining randomized control data, single arm phase II trials, several recently published meta-analyses, as well as retrospective data where there is no clinical trial data available. The role of positron emission tomography (PET) will be reviewed as well. RESULTS: Current data support the role of neoadjuvant chemoradiotherapy followed by surgical resection for locally advanced esophageal cancer with 3-year overall survival ranging from 30% to 60%. The benefit of adjuvant chemoradiation therapy is limited to margin positive and/or node positive patients. There is emerging data questioning the survival benefit of surgical resection after chemoradiotherapy. External beam radiation therapy alone results in very few long-term survivors and is considered palliative at best. Radiation dose-escalation has failed to improve local control or survival. PET scanning is vital in staging and has become a strong predictor of response and survival. CONCLUSIONS: Preoperative or definitive concurrent chemoradiotherapy is the established standard of care for locally advanced cancers of the esophagus. While preoperative chemotherapy is supported by level 1 evidence, the true benefit of induction chemotherapy before chemoradiotherapy has not been established in a prospective randomized control trial. The role of surgery in the management of SCC is still a hotly debated subject, however, it is still recommended for AC. There is no data to support adjuvant chemotherapy after preoperative chemoradiotherapy. The benefit of neoadjuvant chemotherapy seems to be limited AC. Radiation without chemotherapy is palliative and never curative. PET continues to be integrated into treatment decisions and predicts for response and survival after therapy.

A qualitative study on the experiences of female firefighters.

PURPOSE: Firefighters are exposed to high physical and psychological occupational factors while providing an essential service to our communities. Female firefighters represent a minority group in this male dominated occupation. The purpose of this study was to qualitatively determine the impact of a male dominated, physically demanding occupation on women's work health and job satisfaction through the experiences of female firefighters. METHODS: A phenomenological approach was used to collect data through semi-structured, recorded interviews with female firefighters. The recorded interviews were transcribed into text and inductive thematic analysis was used to qualitatively analyze the transcripts. RESULTS: Review and analysis of the participant responses identified seven themes: physical demands/difficulties, gender related physiological differences, compensatory strategies, equipment mal-adaptation, earning respect, negative attitudes of male counterparts: impact on social inclusion and health behaviors, recognition of injury risk. CONCLUSION: Female firefighters are exposed to increased risk of injury due to the psychological and physical occupational stressors in firefighting. Implications of this research are provided and include recommendations for future research to target the physical and psychosocial aspects of firefighting.

Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation.

PURPOSE: To develop an evidence-based guideline for the empiric management of pediatric fever and neutropenia (FN). METHODS: The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group composed of experts in pediatric oncology and infectious disease as well as a patient advocate. The Panel was convened for the purpose of creating this guideline. We followed previously validated procedures for creating evidence-based guidelines. Working groups focused on initial presentation, ongoing management, and empiric antifungal therapy. Each working group developed key clinical questions, conducted systematic reviews of the published literature, and compiled evidence summaries. The Grades of Recommendation Assessment, Development, and Evaluation approach was used to generate summaries, and evidence was classified as high, moderate, low, or very low based on methodologic considerations. RESULTS: Recommendations were made related to initial presentation (risk stratification, initial evaluation, and treatment), ongoing management (modification and cessation of empiric antibiotics), and empiric antifungal treatment (risk stratification, evaluation, and treatment) of pediatric FN. For each recommendation, the strength of the recommendation and level of evidence are presented. CONCLUSION: This guideline represents an evidence-based approach to FN specific to children with cancer. Although some recommendations are similar to adult-based guidelines, there are key distinctions in multiple areas. Implementation will require adaptation to the local context.

Absent infrarenal inferior vena cava.

Absence of an infrarenal inferior vena cava is an infrequent finding on computed tomography scans and is usually an unexpected, incidental finding. This report concerns a young patient with an absent infrarenal inferior vena cava who presented with abdominal and back pain.

Porcelain atrium: a case report with literature review.

Massive left atrial wall calcification, or porcelain atrium, is very rare. We describe a case of an unusual pattern of cardiac calcification demonstrated on routine preoperative chest X-ray for cataract surgery in a 71-year-old Nigerian woman. Past medical history was significant for mitral stenosis and atrial fibrillation. Radiographic imaging revealed curvilinear high density areas of calcification outlining the left atrium on the chest X-ray. Noncontrast CT scan of the thorax confirmed the left atrial distribution of calcification and, thus, the diagnosis of porcelain left atrium.

Interrelation of saturated fat, trans fat, alcohol intake, and subclinical atherosclerosis.

BACKGROUND: Intake of saturated fat, trans fat, and alcohol alter cardiovascular disease risk, but their effect on subclinical atherosclerosis remains understudied. OBJECTIVE: The objective was to examine and quantify the interrelation of saturated fat, trans fat, alcohol intake, and mean carotid artery intimal medial thickness (IMT). DESIGN: We conducted a population-based, cross-sectional study among 620 persons of Aboriginal, South Asian, Chinese, or European origin aged 35-75 y, who had lived in Canada for >or=5 y. Mean IMT was calculated from 6 well-defined segments of the right and left carotid arteries with standardized B-mode ultrasound, and saturated fat, trans fat, and alcohol intakes were measured with validated food-frequency questionnaires. RESULTS: For every 10-g/d increase in saturated fat intake, IMT was 0.03 mm higher (P=0.01) after multivariate adjustment. A 1-g/d higher intake of trans fat was associated with a 0.03-mm higher IMT (P=0.02) after multivariate adjustment. The ratio of polyunsaturated to saturated fat (P:S) was inversely associated with IMT after multivariate adjustment (change in IMT: -0.06 mm; P<0.01). Saturated and trans fat intakes were independently associated with IMT thickness (change in IMT: 0.03 mm; P<0.01 and 0.02, respectively; P for interaction=0.01). Polyunsaturated, monounsaturated, cholesterol, and total fat intakes were unrelated to IMT. The relation between saturated fat intake and IMT strengthened (beta=0.0066, P<0.001) in persons who never or rarely consumed alcohol as compared with moderate or heavy drinkers (beta=0.0001, P=0.79, P for interaction=0.01). CONCLUSION: Higher habitual intakes of saturated and trans fats are independently associated with increased subclinical atherosclerosis, and alcohol intake may attenuate the relation between saturated fat and subclinical atherosclerosis.

Defining obesity cut points in a multiethnic population.

BACKGROUND: Body mass index (BMI) is widely used to assess risk for cardiovascular disease and type 2 diabetes. Cut points for the classification of obesity (BMI >30 kg/m2) have been developed and validated among people of European descent. It is unknown whether these cut points are appropriate for non-European populations. We assessed the metabolic risk associated with BMI among South Asians, Chinese, Aboriginals, and Europeans. METHODS AND RESULTS: We randomly sampled 1078 subjects from 4 ethnic groups (289 South Asians, 281 Chinese, 207 Aboriginals, and 301 Europeans) from 4 regions in Canada. Principal components factor analysis was used to derive underlying latent or "hidden" factors associated with 14 clinical and biochemical cardiometabolic markers. Ethnic-specific BMI cut points were derived for 3 cardiometabolic factors. Three primary latent factors emerged that accounted for 56% of the variation in markers of glucose metabolism, lipid metabolism, and blood pressure. For a given BMI, elevated levels of glucose- and lipid-related factors were more likely to be present in South Asians, Chinese, and Aboriginals compared with Europeans, and elevated levels of the blood pressure-related factor were more likely to be present among Chinese compared with Europeans. The cut point to define obesity, as defined by distribution of glucose and lipid factors, is lower by approximately 6 kg/m2 among non-European groups compared with Europeans. CONCLUSIONS: Revisions may be warranted for BMI cut points to define obesity among South Asians, Chinese, and Aboriginals. Using these revised cut points would greatly increase the estimated burden of obesity-related metabolic disorders among non-European populations.