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Background Suppurative intracranial complications of sinusitis are rare events in children and can lead to harmful neurologic sequelae and significant morbidity. We sought to review the presentation and management of patients admitted at our hospital with these conditions. Methods This was a retrospective study of pediatric patients admitted to a quaternary children’s hospital from 2007 to 2019 for operative management of sinusitis with intracranial extension. Clinical characteristics, including surgical and microbiological data, were collected and analyzed. Results Fifty-four patients were included; the median age was 11.0 years, and there was a male predominance. Eighty-nine percent of patients had prior healthcare visits for the current episode of sinusitis; 46% of patients had an abnormal neurologic exam on admission. Epidural abscess and subdural empyema were the most common complications, and subdural empyema was associated with repeat surgical intervention. The dominant pathogens were Streptococcus anginosus group organisms (74%). The majority of patients completed treatment parenterally, with a median duration of therapy of 35 days. Neurological sequelae, including epilepsy or ongoing focal deficits, occurred in 22% of patients. History of seizure or an abnormal neurological exam at admission were associated with neurological sequelae. Conclusions Clinicians should consider intracranial complications of sinusitis in patients with symptoms of sinusitis for >1 week. Patients should undergo urgent neuroimaging, as neurosurgical intervention is essential for these patients. Subdural empyema was associated with repeat neurosurgical intervention. Neurological sequelae occurred in 22% of patients, and new onset seizure or an abnormal neurological exam at admission were associated with neurological sequelae.

BACKGROUND Exhaled nitric oxide (eNO) is a known biomarker for the diagnosis and monitoring of bronchial hyperreactivity in adults and children. AIMS To investigate the potential role of eNO measurement for predicting perioperative respiratory adverse events in children, we sought to determine its feasibility and acceptability before adenotonsillectomy. METHODS We attempted eNO testing in children, 4-12 years of age, immediately prior to admission for outpatient adenotonsillectomy. We used correlations between eNO levels and postoperative adverse respiratory events to make sample size predictions for future studies that address the predictability of the device. RESULTS One hundred and three (53%) of 192 children were able to provide an eNO sample. The success rate increased with age from 23% (9%-38%) at age 4 to over 85% (54%-98%) after age 9. Using the eNO normal value (

Background. The combination of chemotherapy plus anti HER-2 agents is the mainstay of HER-2 positive advanced breast cancer (ABC) therapy. We conducted a phase II trial testing activity and safety of trastuzumab and metronomic capecitabine/cyclophosphamide (HEX) as first-line therapy in HER-2 positive ABC. Methods. Patients at first relapse or with synchronous metastasis were treated with trastuzumab (4 mg/kg, biweekly) plus oral capecitabine (1500 mg/daily) and cyclophosphamide (50 mg/daily). Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival (PFS), clinical benefit rate (CBR; PR + CR + SD for ≥ 24 weeks) and tolerability. Optimal two-stage design was applied. Results. Sixty patients with measurable ABC, tumors scored as +3 for HER-2 or FISH +, untreated for advanced disease were enrolled. Median age was 62.5 years, visceral metastases were present in most patients (57.9%). Median number of cycles was 16 (range 1–98). ORR was 56.7% (95% CI, 44.1–68.4%), with 5 CR (8.3%) and 29 PR (48.3%). Fifteen patients had SD (25%). The CBR was 78.2%. Nine progressions were observed (15%). Median PFS was 11 months. One year PFS was 47.7%. Median OS was 45.9 months. Worst toxicities were grade 3 hand-foot syndrome in 2 pts (3.3%), grade 3 anaemia in 2 pts (3.3%), grade 2 nausea in 2 pts (3.3%) and grade 3–4 diarrhea in 2 pts (3.3%). Cardiac toxicity grade 1 was reported in 1 pt. Conclusions. Combination of trastuzumab and metronomic oral chemotherapy has clinical activity. The tolerability was excellent and allowed the prolonged delivery of treatment., Highlights • Combination of chemotherapy plus anti HER-2 agents is the standard treatment of HER-2 positive breast cancer. • Combination of trastuzumab and metronomic chemotherapy is an alternative therapeutic approach. • Metronomic therapy allows long-term administration of drugs. • Mild toxicity in advanced breast cancer is desirable.

Background The extent of surgery required in the management of pediatric non-medial subperiosteal orbital abscess (SPOA) due to medically refractory complicated acute sinusitis is unknown. Objectives The primary objective is to compare operative outcomes of children treated with combined endoscopic sinus surgery (ESS) and external orbital drainage (EOD) versus those treated with EOD alone. Methods Retrospective case series from a tertiary children’s hospital analyzing outcomes in children requiring surgical management for acute sinusitis complicated by non-medial SPOA between November 2007 and September 2019. Results Sixteen children with a mean age of 9.4 years (95% CI: 7.3–11.4) met inclusion. Eleven (68.8%) underwent combined EOD and ESS, while five (31.2%) underwent EOD alone. Groups were similar in age, symptom duration, white blood cell count, C-reactive protein level, intraocular pressure, Lund-Mackay score, and abscess volume. There was no significant difference in median length of stay between patients treated with a combined approach versus those treated by EOD alone. Cultures identified non-beta-hemolytic Streptococcus species in 56.3% of patients, with Streptococcus intermedius representing the most common organism in 37.5%. In one case, ESS identified a pathogen not acquired via concomitant EOD, which did influence management. No child required a subsequent surgical procedure and there were no operative complications. Conclusions The addition of ESS in the management of pediatric non-medial SPOA was not associated with a statistically different duration of hospitalization. Cultures from concomitant ESS rarely aided in diagnosis or antibiotic therapy. Further study should delineate the indications for ESS in these cases.

The coronavirus disease 2019 (COVID-19) pandemic requires clinicians to explore alternatives to routine patient management. Otolaryngologists caring for children commonly depend on physical examination, laboratory data, and ambulatory surgical procedures. Limiting patient care, mindful allocation of resources, and concern for safety have challenged all aspects of our health care system. This evidence-based clinical consensus is designed to guide practitioners of pediatric otolaryngology for common scenarios during this time.Peer-reviewed literature, published reports, institutional guidelines, and expert consensus.A clinical consensus on 6 common scenarios in pediatric otolaryngology developed with evidence-based strategies.Providers should suspend all in-person nonessential office visits and elective surgical procedures. An emphasis on medical management and caregiver education will provide reasonable approaches to many of the common outpatient concerns. Surgery for chronic otitis media, obstructive sleep apnea, and acute rhinosinusitis should occur only in response to severe complications or failure of medical regimens. The approach to the pediatric neck mass focuses on timely management for oncologic etiologies and cautious surgical intervention for abscess drainage or tissue sampling. Finally, epistaxis and otorrhea must be triaged and addressed without the usual ambulatory procedures.Adaptation of practice patterns during this unprecedented moment for our health care system requires thoughtful planning. The strategies described allow for safe handling of common pediatric otolaryngology diagnoses. Ultimately, otolaryngologists must be stewards of our global health community while advocating for the care of individual pediatric patients.

Introduction Invasive fungal sinusitis (IFS) is a rare but deadly clinical entity that occurs in immunocompromised patients. Diagnosis in children typically requires operative biopsies under general anesthesia, which has associated risks. Findings on bedside nasal endoscopy (BNE) can be used with history, exam, and imaging to determine the need for surgery, however, the accuracy of this tool has not been established among pediatric patients. Methods Patients who underwent BNE for evaluation of IFS from 2008 to 2016 at the Children's Hospital of Philadelphia were identified using Current Procedural Terminology (CPT) codes. Retrospective chart analysis was performed and included underlying diagnoses, presenting signs and symptoms, imaging findings, endoscopic findings and outcomes. Results Nineteen patients were identified who underwent evaluation for IFS using BNE during the period studied. Eight patients had exam findings that were concerning for IFS, including debris or crusting, darkened or pale mucosa, or copious, thick and/or purulent secretions. Immediate operative biopsies and debridement revealed IFS in six of eight patients. Eleven patients had exam findings deemed not concerning for IFS including mucosal edema, mucous without purulence, or normal findings. Six of eleven patients underwent operative biopsy despite negative endoscopy, and five were observed clinically. None of the 11 patients with negative bedside endoscopy developed IFS. Conclusions All patients with IFS had concerning exam findings on endoscopy and were treated with immediate biopsies and debridement. No patient with normal or non-concerning findings on BNE progressed to have invasive fungal sinusitis. While suspicion for IFS in immunocompromised children must remain high, BNE is feasible and useful in its assessment.

Introduction Biweekly schedule of XELOX-2 (capecitabine plus oxaliplatin) showed interesting results in first-line therapy of patients with metastatic colorectal cancer (mCRC). Bevacizumab plus FOLFOX-4 (oxaliplatin, folinic acid, and infusional 5-fluorouracil) is among standard first-line treatment options in this setting. We performed a phase II randomized trial in order to evaluate the activity of bevacizumab plus either FOLFOX-4 or XELOX-2 in first-line therapy of patients with mCRC. Materials and Methods Patients with mCRC were randomized, in a 1:2 ratio, to first-line bevacizumab plus either FOLFOX-4 (Arm A), as calibration arm, or XELOX-2 (Arm B), up to 12 cycles. Patients without progression were further randomized to maintenance bevacizumab alone or with the same induction fluoropyrimidine. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival, overall survival, and toxicity. The study design was formally non-comparative, but exploratory comparison was performed. Results Forty-five patients were randomized in arm A and 87 in arm B with an ORR of 55.6% versus 48.3% (P = .43), respectively. After a median follow-up of 47.2 months, progression-free survival was 10.0 versus 9.9 months (hazard ratio, 0.96; 95% confidence interval, 0.65-1.41; P = .84) and overall survival was 29.8 versus 25.0 months (hazard ratio, 1.21; 95% confidence interval, 0.77-1.92; P = .41), respectively. The main grade 3 to 4 toxicities (% A/B) were: neutropenia 15/3 and nausea 9/5. Conclusion This exploratory analysis showed that biweekly XELOX-2 plus bevacizumab has a comparable ORR with FOLFOX-4 plus bevacizumab in patients with mCRC.

Objective To provide recommendations to otolaryngologists and allied physicians for the comprehensive management of young infants who present with signs or symptoms of choanal atresia. Methods A two-iterative delphi method questionnaire was used to establish expert recommendations by the members of the International Otolaryngology Group (IPOG), on the diagnostic, intra-operative, post-operative and revision surgery considerations. Results Twenty-eight members completed the survey, in 22 tertiary-care center departments representing 8 countries. The main consensual recommendations were: nasal endoscopy or fiberscopy and CT imaging are recommended for diagnosis; unilateral choanal atresia repair should be delayed after at least age 6 months whenever possible; transnasal endoscopic repair is the preferred technique; long term follow-up is recommended (minimum one year) using nasal nasofiberscopy or rigid endoscopy, without systematic imaging. Conclusion Choanal atresia care consensus recommendations are aimed at improving patient-centered care in neonates, infants and children with choanal atresia.

Vascular malformations presenting in the nasal cavity and paranasal sinuses are rare. Differentiating benign vascular malformations of the sinonasal cavity from other pathologic entities can be challenging and the role of preoperative angiography and embolization is not well defined. We present two unique cases of large pediatric sinonasal vascular malformations and describe their presentation, diagnosis and subsequent management. Both patients underwent embolization of the ipsilateral arterial supply followed by successful and complete endonasal surgical excision. This report provides description of management of the very rare occurrence of sinonasal vascular malformation in two adolescents.

Purpose Surgeons resuming elective procedures during the COVID-19 pandemic should consider strategies to mitigate risk of exposure. For otolaryngologists performing surgery on children, unique vulnerability to SARS-CoV-2 results from a regular interface with the upper respiratory tract mucosa. A growing interest in perioperative application of povidone‑iodine (PVP-I) to the nasopharynx and oropharynx has emerged. The purpose of this review is to provide an evidence-based assessment of PVP-I in pediatric oral, nasal and pharyngeal surgery. Methods A contemporary literature review with algorithmic approach to the potential use of PVP-I in pediatric mucosal surgery. Results Several formulations of PVP-I have shown rapid in vitro virucidal activity against SARS-CoV-2. Antisepsis using 1.0% PVP-I mouthwash and 0.45% PVP-I throat spray can occur after 30 seconds of contact time. To date, in vivo effectiveness of PVP-I against SARS-CoV-2 has yet to be established and possible risks of its direct use on upper aerodigestive mucosa of children must be weighed. Conclusion Further research is required prior to strongly recommending PVP-I use in preparation for nasal, oral or pharyngeal surgery in children.

The microbiology of pediatric complicated acute rhinosinusitis (ARS) has evolved, and our current understanding of pathogenic organisms is limited. The objectives of this study are to describe the incidence of pathogens causing complicated ARS requiring surgical intervention at our institution over a 10-year period as well as their associated treatment outcomes.Retrospective cohort study.A single tertiary care children's hospital.Data were reviewed from all patients who underwent surgery for complicated ARS and had positive culture data from 2006 to 2016. Associations among pathogens, complications, and outcomes were analyzed with Pearson χEighty-nine patients met criteria. Complications included orbital infections (78%), intracranial infections (48%), Pott's puffy tumor (13%), and cavernous sinus thrombosis (9.0%). Bacterial isolates were majority polymicrobial (55%) and included Streptococcus species (58%), Staphylococcus species (49%; including methicillin-resistant S aureus [MRSA], 11%), and anaerobic bacteria (35%). S pneumoniae (9.0%), Haemophilus species (4.5%), and Moraxella catarrhalis (1.1%) were relatively uncommon. Bacterial isolates were similar among patients with all types of complications.Among a large cohort of pediatric patients with complicated ARS, most bacterial isolates were polymicrobial, with Streptococcus and Staphylococcus species contributing to the majority of cases. S aureus species, including MRSA and anaerobic pathogens, were common. The pattern of bacterial isolates was similar among patients with all types of complications of ARS. We suggest treatment for complicated ARS with broad-spectrum antibiotics with coverage for Streptococcus species, Staphylococcus species including MRSA, and anaerobic bacteria.

The EPHA2 tyrosine kinase receptor is implicated in tumor progression and targeted therapies resistance. We evaluated EPHA2 as a potential resistance marker to the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in colorectal cancer. We studied activation of EPHA2 in a panel of human colorectal cancer cell lines sensitive or resistant to anti-EGFR drugs. The in vitro and in vivo effects of ALW-II-41-27 (an EPHA2 inhibitor) and/or cetuximab treatment were tested. Formalin-fixed paraffin-embedded tumor specimens from 82 RAS wild-type (WT) metastatic colorectal cancer patients treated with FOLFIRI + cetuximab as first-line therapy in the CAPRI-GOIM trial were assessed for EPHA2 expression by immunohistochemistry and correlated with treatment efficacy. EPHA2 was differentially activated in colorectal cancer cell lines. Combined treatment with ALW-II-41-27 plus cetuximab reverted primary and acquired resistance to cetuximab, causing cell growth inhibition, inducing apoptosis and cell-cycle G1–G2 arrest. In tumor xenograft models, upon progression to cetuximab, ALW-II-41-27 addition significantly inhibited tumor growth. EPHA2 protein expression was detected in 55 of 82 tumor samples, frequently expressed in less-differentiated and left-sided tumors. High levels of EPHA2 significantly correlated with worse progression-free survival [8.6 months; confidence interval (CI) 95%, 6.4–10.8; vs. 12.3 months; CI 95%, 10.4–14.2; P = 0.03] and with increased progression rate (29% vs. 9%, P = 0.02). A specific EPHA2 inhibitor reverts in vitro and in vivo primary and acquired resistance to anti-EGFR therapy. EPHA2 levels are significantly associated with worse outcome in patients treated with FOLFIRI + cetuximab. These results highlight EPHA2 as a potential therapeutic target in metastatic colorectal cancer.

Introduction Cisplatin with pemetrexed (CP) and carboplatin with paclitaxel and bevacizumab (CbTB) are standard first-line treatments for patients with advanced nonsquamous (NS) non–small-cell lung cancer (NSCLC). Quality of life (QoL) is a key objective in the management of advanced NSCLC. Thus, effect on QoL could be an additional factor in the choice of treatment. Patients and Methods Patients with untreated stage IIIB/IV NS-NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomized to receive first-line chemotherapy with cisplatin 75 mg/m 2 and pemetrexed 500 mg/m 2 , every 3 weeks, for 6 cycles followed by maintenance pemetrexed; or carboplatin area under the curve 6, paclitaxel 200 mg/m 2 , and bevacizumab 15 mg/kg, every 3 weeks, for 6 cycles followed by maintenance bevacizumab. The primary end point was the difference in QoL between the 2 treatment arms after 12 weeks of maintenance, measured using the EuroQoL 5 Dimensions-Index (EQ5D-I) and EQ5D-visual analogue scale (EQ5D-VAS). Results One hundred eighteen patients were randomized to CP (n = 60) or CbTB (n = 58). Baseline characteristics were well balanced. The proportion of patients evaluable for the primary end point was lower than planned. After 12 weeks of maintenance, the difference between mean changes in EQ5D-I was 0.137, favoring CP (95% confidence interval [CI], −0.02 to 0.29, Wilcoxon P = .078), although not statistically significant; and the difference between mean changes in EQ5D-VAS was 0.97 (95% CI, −9.37 to 11.31, Wilcoxon P = .41). Conclusion Although the study was underpowered because of a small number of patients evaluable for the primary end point, QoL did not differ between treatment arms. Other factors such as comorbidities and schedule should be used when deciding on first-line treatment.

Background Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy. Patients and methods In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing. Results A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P

Background Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. Patients and methods We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progression-free survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. Results Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7–8.0] versus 4.5 months (95% CI 3.3–5.7); [hazard ratio (HR), 0.81; 95% CI 0.58–1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5–8.2) versus 5.3 months (95% CI 3.7–6.9); HR, 0.56 (95% CI 0.33–0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4–28.0) versus 19.8 months (95% CI 14.9–24.7); HR, 0.57 (95% CI 0.32–1.02); P = 0.056]. Conclusions Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials.

Objective To describe our outcomes after laryngotracheal reconstruction that required posterior costal cartilage grafting focused on decannulation rates and complications. Study Design Case series with chart review. Subjects and Methods Charts were reviewed on 58 patients. Operation specific and overall decannulation rates were determined. Complications were reviewed and correlated with technique of graft placement. Available voice outcomes were reviewed. Results Forty-eight patients were included. There was no statistically significant correlation between degree of stenosis and rate of decannulation. The overall decannulation rate, regardless of number of surgeries performed, was 96 percent. The relative risk for complications was higher among children who had a sutured versus a sutureless flanged posterior graft (RR = 2.5, P Conclusions Operation-specific decannulation rates are not significantly different with increasing disease severity, although the power to detect small differences in this study is low. Sutureless graft placement is associated with a lower complication rate. Supraglottic compression is a common postoperative compensatory vocal behavior and may correlate with disease severity.

Cochlear implantation is increasingly being performed in children with inner ear malformations. In severe cochleovestibular anomalies, such as severe partitioning defects and common cavity dysplasia, positioning of the electrode array can be hazardous, with inadvertent placement into the internal auditory canal (IAC) or carotid canal being well known. We describe a case in which real-time intraoperative computed tomographic scanning was used to help achieve proper electrode positioning in a child with a severe malformation.Child with common cavity malformations undergoing cochlear implantation.Intraoperative computed tomography used during implantation procedure.Use of technique in determining electrode position.A 10-year-old patient with bilateral common cavity malformations presented with declining performance in a functioning implant placed 7 years earlier. The family elected implantation of the contralateral ear. Via a posterior labyrinthotomy approach, a straight array was placed into the common cavity. Intraoperative computed tomographic scanning was immediately performed on the operating room table, showing that the array was in the IAC. A second attempt with a different insertion angle also resulted in IAC placement. In a third attempt, the electrode was advanced as a loop, grasping the tip through an adjacent second labyrinthotomy. Computed tomography confirmed good position against the outer wall of the cavity.Real-time intraoperative computed tomography is a new technology with many potential applications in surgery. In our patient, it allowed rapid and accurate determination of electrode position and helped achieve ideal placement in a severely malformed inner ear.

To determine the pediatric age groups viable for nasoseptal flap (NSF) reconstruction of endoscopic endonasal approaches (EEA) to intracranial pathology of suprasella neoplasms.Retrospective cohort study.Retrospective review of 16 pediatric patients who underwent EEA with NSF reconstruction for a suprasellar defect from 2012 to 2014. Radioanatomic analysis was utilized to assess feasibility of NSF reconstruction of suprasellar neoplasms approached via EEA. Computed tomography (CT) measurements for defect size and potential flap coverage were measured by preoperative maxillofacial CT. Radiographic measurements and surgical outcomes were compared to determine if flap size would be sufficient to cover said defects in two pediatric age groups: those10 years of age (mean age 14 years) and those10 years (mean age 6 years).Of all patients encountered in this cohort, one postoperative cerebrospinal fluid leak was identified in the10 years of age population, and this was not due to insufficient flap coverage. Average potential flap length and width are sufficient to cover average suprasellar defect length and width in both age groups (P.05 in all age groups).Patient selection is critical for successful pediatric EEA. Preoperative radiographic assessment of NSF feasibility is a critical to ensure adequate flap coverage for suprasellar defects. NSF appears to provide a sufficient and reliable coverage option in reconstruction of suprasellar defects in pediatric patients.4.

More than 500,000 children undergo tonsillectomy each year in the United States. Although prior studies suggest that most patients received perioperative antibiotics, practice varies across centers. In 2011, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) published a practice guideline recommending against perioperative antibiotic use for pediatric tonsillectomy. The impact of this recommendation has not been thoroughly examined.To determine the impact of the AAO-HNS guideline on the use of perioperative antibiotics and patient outcomes for pediatric tonsillectomy.This was a quasi-experimental study including 9265 children who underwent routine tonsillectomy from January 2009 through August 2012 within a large pediatric health care network containing hospital-based and ambulatory surgical facilities. Data were collected from a shared electronic health record and validated through manual medical record review. We used an interrupted time series analysis with segmented logistic regression and a nonequivalent dependent variable (tympanoplasty) to assess acute changes and differences in trends over time relative to guideline publication.Publication of the AAO-HNS clinical practice guideline.The primary outcome was antibiotic administration on the day of surgery. Secondary outcomes included otolaryngology clinic encounters, emergency department encounters, hospital admissions, and surgical procedures for bleeding in the 30 days following tonsillectomy.Of 9265 tonsillectomies during the study period, 5359 met inclusion criteria. Immediately after guideline publication, perioperative antibiotic use dropped by 86.5% (P .001) and was sustained throughout the postintervention period. Rates of otolaryngology clinic encounters, emergency department encounters, and hospital admissions did not change significantly over time. There was a small but statistically significant increase in surgical procedures for bleeding following the intervention from 1.35% (95% CI, 0.57%-2.14%) to 3.48% (95% CI, 1.85%-5.10%).AAO-HNS guideline publication decreased perioperative antibiotic use for pediatric tonsillectomy across a large pediatric health care network. Although there were no changes in otolaryngology clinic visits, emergency department visits, or admissions, we found a small but significant increase in surgery for bleeding following guideline publication. Additional studies are necessary to verify this unexpected association.

Background: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to assess potential clinical implications. Patients and methods: Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculated by multiplying by 2 the frequency of mutant alleles in neoplastic cells. Therefore, HS virtually corresponds to the fraction of neoplastic cells carrying a specific mutation. Results: The KRAS HS ranged between 12 and 260 with mean value of 87.1 and median value of 84.4, suggesting that in most CRC, the majority of neoplastic cells carry mutant KRAS. Similar findings were observed for NRAS (HS range 35.5-146.7; mean 102.8; median 117.1). In contrast, in BRAF (HS range 17.1-120; mean 54.8; median 54.3) and PIK3CA (HS range 14.3-120; mean 59.5; median 47.3) mutant cases, only a fraction of neoplastic cells seem to carry the mutant allele. The response rate was 70% in KRAS mutant patients with an HS 33 patients (high KRAS; n = 35); median progression-free survival were 7.97 and 8.37 months, respectively. Low-KRAS tumors had a higher frequency of additional mutations in PIK3CA when compared with high-KRAS (6/10 versus 8/35). Conclusions: KRAS and NRAS mutations are usually present in the majority of neoplastic cells, whereas BRAF and PIK3CA mutations often affect a limited fraction of transformed cells. Resistance to cetuximab in low-KRAS patients might be driven by the complex mutational profile rather than KRAS mutation load.

Retrospective studies have limitations in predicting perioperative risk following adenotonsillectomy in children with obstructive sleep apnea syndrome (OSAS). Few prospective studies exist. We hypothesized that demographic and polysomnographic (PSG) variables would predict respiratory and general perioperative complications.Prospective, observational cohort study.Pediatric tertiary center.Consecutive children undergoing adenotonsillectomy for OSAS within 12 months of PSG were evaluated for complications occurring within 2 weeks of surgery.There were 329 subjects, with 27%3 years old, 24% obese, 16% preterm, and 29% with comorbidities. In this higher risk population, 28% had respiratory complications (major and/or minor), and 33% had nonrespiratory complications. Significant associations were found between PSG parameters and respiratory complications as follows: apnea hypopnea index (rank-biserial correlation coefficient [r] = 0.174, P = .017), SpO2 nadir (r = -0.332, P.0005), sleep time with SpO290% (r = 0.298, P.0005), peak end-tidal CO2 (r = 0.354, P.0005), and sleep time with end-tidal CO250 mm Hg (r = 0.199, P = .006). Associations were also found between respiratory complications and age3 years (r = -0.174, P = .003) or black race (r = 0.123, P = .039). No significant associations existed between PSG parameters and nonrespiratory complications. A model using age3 years, SpO2 nadir, and peak CO2 predicted respiratory complications better than the American Academy of Pediatrics or American Academy of Otolaryngology-Head and Neck Surgery Foundation guidelines but was imperfect (area under the curve = 0.72).Thus, PSG predicted perioperative respiratory, but not nonrespiratory, complications in children with OSAS. Age3 years or black race are high-risk factors. Present guidelines have limitations in determining the need for postoperative admission.

Treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies has been restricted to metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors. Next-generation sequencing (NGS) allows the assessment in a single analysis of a large number of gene alterations and might provide important predictive and prognostic information.In the CAPRI-GOIM trial, 340 KRAS exon 2 wild-type mCRC patients received first-line FOLFIRI plus cetuximab. Tumor samples (182/340, 53.5%) were assessed by NGS to search for mutations in 22 genes involved in colon cancer.Objective responses in the NGS cohort were observed in 104/182 patients [overall response rate (ORR) 57.1%; 95% confidence interval (95% CI) 52% to 66.4%] with a median progression-free survival (mPFS) of 9.8 (95% CI 8.7-11.5) months. NGS analysis was successfully completed in all 182 samples. One or more gene mutations (up to five) were detected in 124/182 (68.1%) tumors within 14/22 genes for a total of 206 mutations. KRAS exon 2 mutations were identified in 29/182 (15.9%) samples, defined as wild type by local laboratory assessment. Frequently mutated genes were: TP53 (39.6%), KRAS exons 3/4 (8.8%), NRAS exons 2/3 (7.1%), PIK3CA exons 9/20 (13.2%), BRAF (8.2%). FOLFIRI plus cetuximab treatment determined ORR of 62.0% (95% CI 55.5% to 74.6%) with mPFS of 11.1 (95% CI 9.2-12.8) months in patients with KRAS and NRAS wild-type tumors. Conversely, ORR was 46.6% (95% CI 39.9-57.5%) with mPFS of 8.9 (95% CI 7.4-9.6) months in patients with KRAS or NRAS mutations. Similarly, the subgroup of patients carrying KRAS, NRAS, BRAF, or PIK3CA mutations showed a worse outcome, although this might be due to a prognostic effect.This study demonstrates that NGS analysis in mCRC is feasible, reveals high level of intra and intertumor heterogeneity, and identifies patients that might benefit of FOLFIRI plus cetuximab treatment.

We report an episode of transient, severe hypertension occurring within 2 minutes of injection of 1% lidocaine with 1:100 000 U of epinephrine in a patient taking midodrine for orthostatic hypotension. We hypothesize that the patient's autonomic nervous system was dangerously susceptible to the effect of local anesthetic when combined with the vasoactive systemic effect of midodrine. Surgeons should minimize the use of vasoconstrictors in patients treated with midodrine to avoid hypertensive complications.

Purpose of review The timing and role of surgery in the management of pediatric chronic rhinosinusitis (pCRS) remains unclear. This review attempts to summarize the existing literature regarding this topic. Recent findings pCRS is a complex clinical syndrome that results from multiple potential causes. Multimodal medical therapy is the accepted primary treatment. Adenoidectomy continues to be the appropriate first-line surgical therapy, and the addition of antral lavage or balloon dilation to this procedure may improve outcomes. Functional endoscopic sinus surgery (FESS) in children is safe and effective in relieving symptoms in the majority of patients. Failure to respond to maximal medical therapy continues to be a commonly cited, although poorly defined, requisite for proceeding to surgery. Recent literature has been focused on the outcomes after FESS rather than specifically defining when this intervention should be considered. Nevertheless, the literature seems to continue to support FESS in children with persistent symptoms despite adenoidectomy and appropriate medical treatment for pCRS. As the symptoms of chronic rhinosinusitis (CRS) may result from multiple underlying causes, clinicians must understand that the role and timing of surgery may vary with particular patients' disease. Summary Surgical management of CRS in children continues to be a frequent topic of study in the otolaryngology literature. As recent research tends to be focused on outcomes after surgery, further prospective studies comparing surgical versus nonsurgical treatment of CRS will likely be required to better define indications for proceeding to surgery at all.

Purpose The aim of the study was to determine the prognostic impact of preepiglottic space (PES) involvement on local failure after concurrent chemoradiation therapy for squamous cell carcinoma. Materials and methods Retrospective chart review of patients who underwent concurrent chemoradiation therapy for T3 or T4 laryngeal, T4 hypopharyngeal, and T3 or T4 oropharyngeal squamous cell carcinoma were eligible for inclusion. Patients were then stratified by the presence or absence of PES tumor involvement. A multivariate analysis was performed on the presence of recurrence using the following pretreatment variables: PES involvement, tumor extent, pathologic cell differentiation, lymph node involvement, age, and sex. Results A total of 102 patients were included in the study. Twenty-seven (28%) patients had documented PES involvement. Mean follow-up for all patients was 46 months. Involvement of the PES was not significantly associated with local tumor persistence or recurrence ( P = .69). No other variables significantly impacted tumor recurrence. Conclusion Preepiglottic space involvement does not negatively impact local tumor control after concurrent chemoradiation therapy.

In the past, hemlock poisoning was only known for its neurotoxic effects; quite recently non-neurological features, consisting of rhabdomyolysis and acute renal failure, have been also described. Here we report our experience with these clinical findings, which we frequently observe in accidental hemlock poisoning. Between 1972 and 1990 we studied 18 patients: 17 of them were poisoned by conline (an alkaloid of Conium maculatim) in Apulia (Italy), and one by cicutoxin (the active principle of water hemlock) in New Mexico (USA). In the non-rapidly-fatal cases we tested myoglobinuria, serum muscle enzymes, and renal function. In the patients with acute renal failure we performed microscopical examination of kidney specimens; immunohistochemistry was carried out to identify myoglobin and actin in tubules. Coniine was detected in urine, serum, or tissues. Neurological features were present in all of our cases: coniine had a curare-like effect on the neuromuscular junction, whereas cicutoxin was convulsant on the central nervous system. In addition rhabdomyolysis was noted in the 17 subjects poisoned by coniine. Acute renal failure was observed in five patients; it was confirmed by histological evidence of tubular necrosis with intratubular deposition of myoglobin and actin released by rhabdomyolysis. Our cases seem to be the first with histopathologically proven acute tubular necrosis in coniine intoxication. In conclusion, in hemlock poisoning neurotoxic manifestations may be accompanied by rhabdomyolysis and acute tubular necrosis; increased awareness of these clinical features is recommended in order to improve the diagnostic and therapeutic procedure.

We report the clinical and histological findings in patients with acute renal failure caused by the ingestion of wildfowl who had eaten hemlock buds. Neurotoxic effects were accompanied by rhabdomyolysis, myoglobinuria, and acute tubular necrosis. Histological studies showed diffuse degeneration of the tubular epithelium. Immunohistological studies demonstrated the presence of myoglobin and actin in renal tubular cells.

One oral dose of 1,000 mg of acetazolamide caused an acute 38% increase in cerebral blood flow (CBF) in eight healthy volunteers. During the following 10 days the subjects took 1,000 mg acetazolamide daily. CBF normalized within the first 2 days. The drug induced mild hyperventilation, gradually decreasing alveolar PCO2 to 70% of the control value at the end of the treatment period. In healthy humans the hyperventilation will not increase brain oxygenation significantly at sea level. But at high altitudes the enhanced ventilatory drive will improve oxygenation of the brain, and this may account for the beneficial effects of the drug on the symptoms of acute mountain sickness. During the treatment there was a significant 10% decrease of the hematocrit but an unaltered hemoglobin concentration. In combination with data in the literature our studies suggest that the initial CBF increase is a consequence of a transient extracellular acidosis dilating brain arterioles, whereas increased ventilatory drive results from a gradually increasing mild intracellular acidosis in the brain.

Myoglobinuria secondary to hypopotassemia was noted in a hypertensive patient treated for a long period with diuretics (chlorthalidone and indapamide). The picture included hypokalemic myopathy, with myoglobinuria, an increase in serum enzymes related by rhabdomyolysis, and flaccid paralysis. In spite of reinstatement management with potassium chloride, hypopotassemia promoted a torsade de pointes, quickly followed by terminal ventricular fibrillation.