Case-Based Clinical Guidance on Dosing and Management of the Hepatic Artery Infusion Chemotherapy Pump.

Hepatic artery infusion (HAI) delivers localized high-dose floxuridine directly to liver tumors through an implanted pump. While patients are undergoing active treatment, the pump is refilled with chemotherapy alternating with saline every 2 weeks using a specialized noncoring needle. Numerous clinical scenarios influence the dosing of floxuridine, which do not conform to the usual dose modification schema for systemic chemotherapy. This article aims to provide practical clinical management solutions to overcome the common challenges faced by oncologists in the real-world management of HAI pump therapy.

First-line regorafenib with nivolumab and chemotherapy in advanced oesophageal, gastric, or gastro-oesophageal junction cancer in the USA: a single-arm, single-centre, phase 2 trial.

BACKGROUND: The addition of nivolumab to chemotherapy improves survival in patients with advanced oesophagogastric (oesophageal, gastric, or gastro-oesophageal junction) adenocarcinoma; however, outcomes remain poor. We assessed the safety and activity of regorafenib in combination with nivolumab and chemotherapy in the first-line treatment of advanced oesophagogastric adenocarcinoma. METHODS: This investigator-initiated, single-arm, phase 2 trial in adult patients (aged ≥18 years) with previously untreated, HER2-negative, metastatic oesophagogastric adenocarcinoma was done at the Memorial Sloan Kettering Cancer Center (New York, NY, USA). Eligible patients had measurable disease or non-measurable disease that was evaluable (defined by Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received FOLFOX chemotherapy (fluorouracil [400 mg/m2 bolus followed by 2400 mg/m2 over 48 h], leucovorin [400 mg/m2], and oxaliplatin [85 mg/m2]) and nivolumab (240 mg) intravenously on days 1 and 15, and oral regorafenib (80 mg) on days 1-21 of a 28-day cycle. Treatment was continued until disease progression (defined by RECIST version 1.1), unacceptable toxicity, or withdrawal of consent. The primary endpoint was 6-month progression-free survival in the per-protocol population (ie, all participants who received a dose of all study treatments). The regimen would be considered worthy of further investigation if at least 24 of 35 patients were progression free at 6 months. Safety was assessed in all participants who received at least one dose of any study treatment. This trial is registered with ClinicalTrials.gov, NCT04757363, and is now complete. FINDINGS: Between Feb 11, 2021, and May 4, 2022, 39 patients were enrolled, received at least one dose of study drug, and were included in safety analyses. 35 patients were evaluable for 6-month progression-free survival. Median age was 57 years (IQR 52-66), nine (26%) patients were women, 26 (74%) were men, 28 (80%) were White, and seven (20%) were Asian. At data cutoff (March 3, 2023), median follow-up was 18·1 months (IQR 12·7-20·4). The primary endpoint was reached, with 25 (71%; 95% CI 54-85) of 35 patients progression free at 6 months. Nine (26%) of 35 patients had disease progression and one (3%) patient died; the death was unrelated to treatment. The most common adverse event of any grade was fatigue (36 [92%] of 39). The most common grade 3 or 4 adverse events were decreased neutrophil count (18 [46%]), hypertension (six [15%]), dry skin, pruritus, or rash (five [13%]), and anaemia (four [10%]). Serious treatment-related adverse events occurred in ten (26%) patients, which were acute kidney injury (three [8%]), hepatotoxicity (two [5%]), sepsis (two [5%]), dry skin, pruritus, or rash (one [3%]), nausea (one [3%]), and gastric perforation (one [3%]). There were no treatment-related deaths. INTERPRETATION: Regorafenib can be safely combined with nivolumab and chemotherapy and showed promising activity in HER2-negative metastatic oesophagogastric cancer. A randomised, phase 3 clinical trial is planned. FUNDING: Bristol Myers Squibb, Bayer and National Institutes of Health/National Cancer Institute.

Neighborhood Characteristics and the Burden of E-Cigarette, or Vaping, Product Use-Associated Lung Injury: An Ecological Comparison Study.

Purpose: E-cigarette, or vaping, product use-associated lung injury (EVALI) is a severe consequence of vaping first described in 2019. Investigating associations between neighborhood-level characteristics and EVALI cases is an important step in identifying at-risk communities to implement future targeted prevention programs. Methods: We retrospectively identified 41 adolescents <19 years hospitalized for treatment for EVALI at Children's Medical Center Dallas from December 2018 to June 2021. Patient ZIP codes were extracted from the electronic medical record and were compared with Dallas area ZIP codes containing no EVALI cases. Socioeconomic status (SES) characteristics were obtained from the 2019 American Community Survey, and they were mapped for ZIP codes using ESRI ArcMap geospatial processing software. A parallel analysis was conducted utilizing data of adolescents hospitalized with appendicitis. Results: Ninety-five percent of our cohort used tetrahydrocannabinol-containing products, and 66% obtained their vaping products from informal sources. EVALI cases were less likely to reside in higher SES ZIP codes as measured by the proportion of the population with at least a high school education (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92-0.99), access to broadband access (OR: 0.95, 95% CI: 0.91-0.99), and private health insurance (OR: 0.97, 95% CI: 0.95-0.99). Alternatively, they were more likely to reside in lower SES ZIP codes as measured by proportion of the population without any health insurance (OR: 1.07, 95% CI: 1.01-1.12). No neighborhood level low SES characteristics were associated with appendicitis hospitalizations. Conclusions: Although small in magnitude, EVALI cases were associated with lower SES ZIP codes but not with vape shop density.

E-cigarettes and asthma in adolescents.

PURPOSE OF REVIEW: E-cigarettes have been long purported to be a mechanism of harm reduction in current smokers. However, market expansion to adolescents has been aggressive, despite government interventions. Research examining the adverse effects of e-cigarettes in teens with asthma has been limited. We discuss the most recent data on the pulmonary manifestations of e-cigarettes use and exposure in adolescents with asthma. RECENT FINDINGS: Adolescents with asthma are more likely to be e-cigarette users than those without asthma and more likely to have asthma exacerbations. Increased pulmonary inflammatory cytokines have been seen in e-cigarette users and mouse models. Yet, providers are not confident in e-cigarette screening and counselling despite acknowledging adolescents are using e-cigarettes regularly. SUMMARY: Since the introduction of e-cigarettes into the United States market in 2007, adolescents use of these products has risen, even after a brief decline during the height of the COVID-19 pandemic. This review will describe the most recent studies on e-cigarette use trends, cytotoxicity of e-cigarette aerosol and associations with the diagnosis and symptoms of asthma. Knowledge gaps, advocacy efforts, evidence on e-cigarette cessation will be highlighted.

Pancreatic cancer: Cutaneous metastases, clinical descriptors and outcomes.

BACKGROUND: Cutaneous metastases in pancreatic cancer (PC) are rare. Herein, we evaluate the clinical, genomic, and other descriptors of patients with PC and cutaneous metastases. METHODS: Institutional databases were queried, and clinical history, demographics, PC cutaneous metastasis details, and overall survival (OS) from cutaneous metastasis diagnosis were abstracted. OS was estimated using Kaplan-Meier methods. RESULTS: Forty patients were identified, and median age (Q1-Q3, IQR) of PC diagnosis was 66.0 (59.3-72.3, 12.9) years. Most patients had Stage IV disease at diagnosis (n = 26, 65%). The most common location of the primary tumor was the tail of the pancreas (n = 17, 43%). The most common cutaneous metastasis site was the abdomen (n = 31, 78%), with umbilical lesions occurring in 74% (n = 23) of abdominal lesions. The median OS (95% CI) was 11.4 months (7.0, 20.4). Twenty-three patients had umbilical metastases (58%), and 17 patients had non-umbilical metastases (43%). The median OS (95% CI) was 13.7 (7.0, 28.7) months in patients with umbilical metastases and 8.9 (4.1, Not reached) months in patients with non-umbilical metastases (p = 0.1). Sixteen of 40 (40%) patients underwent somatic testing, and findings were consistent with known profiles. Germline testing in 12 (30%) patients identified pathogenic variants in patients: CHEK2, BRCA1, and ATM. CONCLUSION: Cutaneous metastases from PC most frequently arise from a pancreas tail primary site and most frequently occur in the umbilicus. Cutaneous metastases may generally be categorized as umbilical or non-umbilical metastases.

Clinical manifestations of EVALI in adolescents before and during the COVID-19 pandemic.

INTRODUCTION: E-cigarette, or vaping, product use-associated lung injury (EVALI) results from inhaling the aerosol of e-cigarettes and has similar clinical features to coronavirus disease 2019 (COVID-19). EVALI case counts since the declaration of the COVID-19 pandemic is unknown. METHODS: A retrospective electronic health record chart review of adolescents hospitalized at one institution with EVALI was conducted. Clinical characteristics and hospital course of patients hospitalized during the pandemic were compared to those prepandemic. RESULTS: The clinical presentation of adolescents hospitalized prior-to (n = 19) and during the COVID-19 pandemic (n = 22) were similar with respect to constitutional, respiratory, and gastrointestinal symptoms. All patients hospitalized during the pandemic were tested for COVID-19 at least once. Only one patient had a positive SARS-CoV-2 RT-PCR test result. Thirty-one out of 39 patients treated with corticosteroids had clinical improvement within 24 h (79%). Patients hospitalized during the pandemic had a shorter median length of stay (5 vs. 7 days, p < 0.01), and were less often discharged with home oxygen (1 vs. 6 patients, p = 0.04). Pulmonary function tests improved pre- to postcorticosteroid treatment and postcorticosteroid to follow-up. CONCLUSIONS: Eliciting a history of vaping in adolescents presenting with constitutional, respiratory, and gastrointestinal symptoms is important to identify EVALI cases, which have continued throughout the COVID-19 pandemic. A shorter length of stay with less need for mechanical ventilation and home oxygen in adolescents hospitalized during the pandemic may reflect increased familiarity with EVALI characteristics. Corticosteroids led to clinical and pulmonary function improvement.

Appendiceal adenocarcinoma found by surgery for acute appendicitis is associated with older age.

BACKGROUND: Appendectomy for acute appendicitis is the most common procedure performed emergently by general surgeons in the United States. The current management of acute appendicitis is increasingly controversial as non-operative management gains favor. Although rare, appendiceal neoplasms are often found as an incidental finding in the setting of appendectomy. Criteria and screening for appendiceal neoplasms are not standardized among surgical societies. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for all patients who underwent appendectomy over a 9-year period (2010-2018). Over the same time period, patients who underwent appendectomy in two municipal hospitals in The Bronx, New York City, USA were reviewed. RESULTS: We found a 1.7% incidence of appendiceal neoplasms locally and a 0.53% incidence of appendiceal tumors in a national population sample. Both groups demonstrated an increased incidence of appendiceal carcinoma by age. This finding was most pronounced after the age of 40 in both local and national populations. In our study, the incidence of appendiceal tumors increased with each decade interval up to the age of 80 and peaked at 2.1% in patients between 70 and 79 years. CONCLUSIONS: Appendiceal adenocarcinomas were identified in patients with acute appendicitis that seem to be associated with increasing age. The presence of an appendiceal malignancy should be considered in the management of older patients with acute appendicitis before a decision to embark on non-operative therapy.

The COVID-19 cannabis health study: Results from an epidemiologic assessment of adults who use cannabis for medicinal reasons in the United States.

Background: Clinical indications for medicinal cannabis include chronic conditions; thus users (MCUs) are at an increased risk of morbidity and mortality resulting from SARS-CoV-2 infection (COVID-19). The study aimed to provide data on cannabis use and self-reported behavioral changes among MCUs with preexisting chronic conditions in response to the pandemic.Methods: An internet-based questionnaire was administered to adults ≥18 who self-reported medicinal cannabis use within the past year. Data are from respondents between March 21 and April 23, 2020; response rate was 83.3%. Health conditions and cannabis frequency, route, and patterns of use were assessed via the COVID-19 Cannabis Health Questionnaire (Vidot et al. 2020).Results: Participants (N = 1202) were predominantly non-Hispanic white (82.5%) and 52.0% male (mean age 47.2 years). Mental health (76.7%), pain (43.7%), cardiometabolic (32.9%), respiratory (16.8%), and autoimmune (12.2%) conditions were most reported. Those with mental health conditions reported increased medicinal cannabis use by 91% since COVID-19 was declared a pandemic compared to those with no mental health conditions (adjusted odds ratio: 1.91, 95% CI: 1.38-2.65). 6.8% reported suspected COVID-19 symptoms. Two percent (2.1%) have been tested for COVID-19 with only 1 positive test result. Some MCUs (16%) changed their route of cannabis administration, switching to nonsmoking forms.Conclusions: The majority of MCUs reported at least one preexisting chronic health condition. Over half report fear of COVID-19 diagnosis and giving the virus to someone else; yet only some switched from smoking to nonsmoking forms of cannabis. Clinicians may consider asking about cannabis use among their patients, particularly those with chronic health conditions.

Oncolytic Reovirus (pelareorep) Induces Autophagy in KRAS-mutated Colorectal Cancer.

PURPOSE: To explore the effects of pelareorep on autophagy in multiple models of colorectal cancer, including patient-derived peripheral blood mononuclear cells (PBMCs). EXPERIMENTAL DESIGN: HCT116 [KRAS mutant (mut)] and Hke3 [KRAS wild-type (WT)] cells were treated with pelareorep (multiplicity of infection, 5) and harvested at 6 and 9 hours. LC3 A/B expression was determined by immunofluorescence and flow cytometry; five autophagic proteins were analyzed by Western blotting. The expression of 88 autophagy genes was determined by qRT-PCR. Syngeneic mouse models, CT26/Balb-C (KRAS mut) and MC38/C57B6 (KRAS WT), were developed and treated with pelareorep (10 × 106 plaque-forming unit/day) intraperitoneally. Protein and RNA were extracted from harvested tumor tissues. PBMCs from five experimental and three control patients were sampled at 0 (pre) and 48 hours, and on days 8 and 15. The gene expression normalized to "pre" was determined using 2-ΔΔC t method. RESULTS: Pelareorep induced significant upregulation of LC3 A/B in HCT116 as compared with Hke3 cells by immunofluorescence (3.24 × and 8.67 ×), flow cytometry (2.37 × and 2.58 ×), and autophagosome formation (2.02 × and 1.57 ×), at 6 and 9 hours, respectively; all P < 0.05. Western blot analysis showed an increase in LC3 A/B (2.38 × and 6.82 ×) and Beclin1 (1.17 × and 1.24 ×) at 6 and 9 hours, ATG5 (2.4 ×) and P-62 (1.52 ×) at 6 hours, and VPS-34 (1.39 ×) at 9 hours (all P < 0.05). Induction of 13 transcripts in cell lines (>4 ×; 6 and 9 hours; P < 0.05), 12 transcripts in CT26 (qRT-PCR), and 14 transcripts in human PBMCs (P < 0.05) was observed. LC3 A/B, RICTOR, and RASD1 expression was upregulated in all three model systems. CONCLUSIONS: Pelareorep hijacks host autophagic machinery in KRAS-mut conditions to augment its propagation and preferential oncolysis of the cancer cells.

E-cigarette or vaping product use-associated lung injury (EVALI) features and recognition in the emergency department.

Since August 2019, the pulmonary disease termed e-cigarette or vaping product-use associated lung injury (EVALI), has resulted in 2758 hospitalizations and 64 deaths in the United States. EVALI is considered in patients who have vaped or dabbed within 90 days of symptom onset, and have abnormal lung imaging in the absence of any pulmonary infection. The majority of EVALI patients are otherwise healthy adolescents and young adults. The leading etiology of EVALI is contamination of delta-9-tetrahydrocannabinoid (THC) e-liquids with vitamin E acetate. Although the exact pathophysiology of vitamin E acetate-induced lung injury is unknown, vitamin E acetate may lead to pulmonary lipid accumulation and/or interfere with surfactant functioning. EVALI symptoms are vague but consist of a constellation of constitutional, pulmonary, and gastrointestinal symptoms. Patients often present multiple times to healthcare facilities as their clinical condition worsens with a considerable mortality risk. The diagnosis of EVALI hinges on obtaining history leading to the recognition of vaping/dabbing. Physicians need to be persistent, but nonjudgmental, in obtaining vaping histories, especially in THC-prohibited states. Radiographical findings of nonspecific bilateral ground-glass infiltrates are best detected on computed tomography. Management for EVALI requires a multidisciplinary approach focused on supportive respiratory care and ruling-out infectious causes. Corticosteroids may be of benefit. Most patients who are hypoxic, have comorbidities, or lack appropriate follow-up within 24-48 hours should be admitted for monitoring. Patients may benefit from substance abuse counseling and should be instructed to avoid vaping. As the outbreak continues, cases should be reported to local health departments and poison control centers.

Clinical Features of E-cigarette, or Vaping, Product Use-Associated Lung Injury in Teenagers.

BACKGROUND: In the United States in 2019, there was an outbreak of electronic cigarette, or vaping, product use-associated lung injury (EVALI). The manifestations of EVALI in adolescents are not well characterized. We describe the diagnosis, evaluation, and management of EVALI in adolescents hospitalized at a tertiary care, university-affiliated children's hospital. METHODS: A multidisciplinary committee developed an EVALI algorithm on the basis of guidelines from the Centers for Disease Control and Prevention. A retrospective chart review was conducted on patients diagnosed with EVALI. Descriptive analyses included sociodemographic characteristics, clinical presentation, laboratory and imaging results, pulmonary function testing, oxygen requirements, and clinic follow-up. RESULTS: Thirteen hospitalized adolescents were diagnosed with confirmed or probable EVALI. The majority were female (54%) with a mean age of 15.9 years. Sixty-nine percent of patients presented with respiratory symptoms, whereas gastrointestinal symptoms were prominent in 85% of patients. Vaping Δ-9-tetrahydrocannabinol was reported in 92% of patients, and vaping nicotine was reported in 62% of patients. All had bilateral ground-glass opacities on the chest computed tomography (CT) scan. Treatment with glucocorticoids led to clinical improvement in 11 of 12 patients. Treatment with glucocorticoids led to improvement in both forced expiratory volume in 1 second and forced vital capacity (P < .05). Four patients required home oxygen on the basis of 6-minute walk test results. CONCLUSIONS: Diagnosis of EVALI should be suspected on the basis of vaping history and clinical presentation. Glucocorticoid treatment led to an improvement in symptoms and lung function. The 6-minute walk test may help determine oxygen needs at discharge.

Pediatric Chest Radiographic and CT Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI).

Background Electronic cigarette or vaping product use-associated lung injury (EVALI) is a serious public health concern with substantial morbidity and mortality, particularly in young individuals. Purpose To evaluate chest radiographic and chest CT findings of EVALI in the pediatric population. Materials and Methods This was a retrospective study of children who presented to a tertiary pediatric hospital from December 2018 to December 2019. Patients fulfilled the Centers for Disease Control and Prevention criteria for EVALI and had chest radiographs and CT images available at initial presentation. Two pediatric radiologists independently reviewed imaging for pattern, distribution, and extent of pulmonary abnormalities, as well as for extrapulmonary abnormalities. Clinical information, management, and outcomes were reviewed. Interobserver agreement was measured with Cohen κ coefficient. Results Seven male patients (50%) and seven female patients (50%) (mean age, 16 years; range, 13-18 years) were evaluated. All patients underwent chest radiography and CT within 4 days of presentation (range, 0-4 days). Chest radiographic findings included ground-glass opacity in 14 of 14 (100%) and consolidation in eight of 14 (57%). CT findings included ground-glass opacity in 14 of 14 (100%), consolidation in nine of 14 (64%), and interlobular septal thickening in two of 14 (14%). At CT, subpleural sparing was seen in 11 of 14 (79%) and a reversed halo sign was seen in five of 14 (36%). Chest radiographic and CT abnormalities were predominately bilateral in 14 of 14 (100%) and symmetric in 13 of 14 (93%), with lower lobe predominance in seven of 14 (50%). Extent of abnormality was predominately diffuse at both chest radiography and CT. There was almost perfect interobserver agreement between two reviewers for detecting abnormalities on chest radiographs (κ = 0.99; 95% confidence interval: 0.97, 1.00) and CT (κ = 0.99; 95% confidence interval: 0.98, 1.00). Conclusion In pediatric patients, electronic cigarette or vaping product use-associated lung injury is characterized by bilateral symmetric ground-glass opacities, consolidation, and a lower lobe predominance at CT. © RSNA, 2020.

Excision repair cross-complementing group-1 (ERCC1) induction kinetics and polymorphism are markers of inferior outcome in patients with colorectal cancer treated with oxaliplatin.

BACKGROUND: ERCC1, a component of nucleotide excision repair pathway, is known to repair DNA breaks induced by platinum drugs. We sought to ascertain if ERCC1 expression dynamics and a single nucleotide polymorphism (SNP) rs11615 are biomarkers of sensitivity to oxaliplatin therapy in patients with colorectal cancer (CRC). METHODS: Western blot and qPCR for ERCC1 expression was performed from PBMCs isolated from patients receiving oxaliplatin-based therapy at specified timepoints. DNA was also isolated from 59 biorepository specimens for SNP analysis. Clinical benefit was determined using progression free survival (PFS) for metastatic CRC. RESULTS: ERCC1 was induced in PBMC in response to oxaliplatin in 13/25 patients with mCRC (52%). Median PFS with ERCC1 induction was 190d compared to 237d in non-induced patients (HR 2.35, CI 1.005-5.479; p=0.0182). ERCC1 rs11615 SNP analysis revealed that 43.3% harbored C/C, 41.2%-T/C and 15.5%-T/T genotype. Median PFS was significantly lower with C/C or T/C (211 and 196d) compared to T/T (590d; p=0.0310). CONCLUSIONS: ERCC1 was induced in a sub-population of patients undergoing oxaliplatin treatment, which was associated with poorer outcome, suggesting this could serve as a marker of oxaliplatin response. C/C or C/T genotype in ERCC1 rs11615 locus decreased benefit from oxaliplatin.

Immunotherapeutic advances in gastrointestinal malignancies.

Cancer is an important global issue with increasing incidence and mortality, placing a substantial burden on the healthcare system. Colorectal cancer is the third most common cancer diagnosed among men and women in US. It is estimated that in 2018 there will be 319,160 new diagnosis and 160,820 deaths related to cancer of the digestive system including both genders in the United States alone. Considering limited success of chemotherapy, radiotherapy, and surgery in treatment of these cancer patients, new therapeutic avenues are under constant investigation. Therapy options have consistently moved away from typical cytotoxic chemotherapy where patients with a given type and stage of the disease were treated similarly, to an individualized approach where a tumor is defined by its specific tissue characteristics /epigenetic profile, protein expression and genetic mutations. This review takes a deeper look at the immune-biological aspects of cancers in the gastrointestinal tract (entire digestive tract extending from esophagus/stomach to rectum, including pancreatico-biliary apparatus) and discusses the different treatment modalities that are available or being developed to target the immune system for better disease outcome.

Pancreatic Cancer Heralded by Worsening Glycemic Control: A Report of Two Cases.

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related death in the United States. Since it is usually diagnosed at an advanced stage, its prognosis remains poor. The initial presentation varies according to the tumor location. The most common presenting signs are weight loss, jaundice, and pain. Several epidemiological, clinical, and experimental studies over the past 2 decades have shown that long-standing diabetes is a modest risk factor for pancreatic cancer. However, new-onset diabetes has also been observed to be an early manifestation of pancreatic cancer. We report 2 cases where worsening glycemic control led to the diagnosis of pancreatic cancer.

Impact of cilia ultrastructural examination on the diagnosis of primary ciliary dyskinesia.

Ultrastructural examination of cilia is the "gold standard" for diagnosing primary ciliary dyskinesia. There is little evidence suggesting the most effective method of procuring a ciliary biopsy and scant benchmark data on rates of conclusive biopsies or on the diagnostic impact of such biopsies. To critically assess rates of inconclusive, positive, and negative ciliary biopsies and to identify clinical factors associated with conclusive results, we reviewed ciliary biopsies submitted for electron microscopy from 2006 to 2011, noting whether specimens were adequate for analysis and whether the ciliary structure was normal. The biopsy site, method used, procedurist's specialty, and clinical diagnoses were determined. Biopsy findings were categorized by diagnostic impact. Over 5 years, 187 patients had 211 biopsies. Conclusive results were obtained on 133/211 biopsies (63%); the remainder were insufficient. The rate of inconclusive biopsies did not vary significantly (P > 0.05; Fisher's exact) among sampling methods. Abnormal results were identified in 8/133 (6.0%) of the adequate specimens. Forceps compared to brush biopsies (abnormal in 4/12 versus 4/121 of the adequate specimens, P  =  0.002), along with multiple biopsy samples (taken on same or different days) compared with a single biopsy sample (abnormal in 3/12 versus 1/110 of the adequate specimens, P  =  0.01), were more likely to yield an abnormal result. Only 63% of pediatric ciliary biopsies provide adequate morphology for analysis, the large majority of these samples showing normal ciliary anatomy. The method of obtaining biopsies did not significantly affect result conclusiveness. Understanding the diagnostic impact of ultrastructural analysis is important as new diagnostic algorithms are developed for primary ciliary dyskinesia.

Impact of environmental controls on childhood asthma.

Exposure to allergens early in life can lead to sensitization and the development of childhood asthma. It is thought that increased exposure with the advent of modern housing is likely contributing to the rise in prevalence of childhood asthma during the past few decades. The progression from allergen exposure to sensitization and asthma development has been noted with respect to dust mites, pets, cockroach, mouse, mold, tobacco smoke, endotoxin, and air pollution, although some have found a protective effect with pet and endotoxin exposure. Recent studies have shown that allergen remediation may be beneficial in reducing asthma morbidity and development, although there is also some evidence to the contrary. Examples of allergen remediation that have been studied include the use of dust mite-impermeable covers, high-efficiency particulate air filtration, integrated pest management, home repairs, ventilation improvement, and pet removal. Several multifaceted, randomized controlled trials have shown that reducing multiple early allergen exposures with environmental controls is associated with a decreased risk of asthma.