Clinical Infectious Diseases

The Association of Antibiotic Stewardship With Fluoroquinolone Prescribing in Michigan Hospitals: A Multi-hospital Cohort Study Abstract Background Fluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown. Methods This study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship. Results There were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003). Conclusions Hospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing.

Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF–identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012–2017: A Retrospective Province-Wide Cohort Study Abstract Background Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. Results Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71). Conclusions Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes. The Association of Antibiotic Stewardship With Fluoroquinolone Prescribing in Michigan Hospitals: A Multi-hospital Cohort Study Abstract Background Fluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown. Methods This study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship. Results There were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003). Conclusions Hospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing. Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF–identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012–2017: A Retrospective Province-Wide Cohort Study Abstract Background Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. Results Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71). Conclusions Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes. Glycocalyx Breakdown is Associated with Severe Disease and Fatal Outcome in Plasmodium falciparum Malaria Abstract Background Interactions between the endothelium and infected erythrocytes, microvascular dysfunction and parasite sequestration play major roles in the pathogenesis of severe falciparum malaria. The glycocalyx is a carbohydrate-rich layer lining the endothelium mediating NO production and vascular homeostasis. The role of the glycocalyx in falciparum malaria and the association with disease severity is not known. Methods We prospectively enrolled Indonesian inpatients (≥18 years old) with severe (SM) or moderately-severe (MSM) falciparum malaria and healthy controls (HCs). Glycocalyx breakdown products were measured in enrolment samples of urine (glycosaminoglycans; dimethylmethylene blue [GAG-DMMB] and liquid chromatography-tandem mass spectrometry [GAG-MS] assays) and plasma (syndecan-1; ELISA), and related to vascular NO bioavailability (reactive hyperemia-peripheral arterial tonometry). Results A total of 129 subjects (SM=43, MSM=57, HC=29) were recruited. Syndecan-1 (µg/ml), GAG-DMMB and GAG-MS (g/mol creatinine) were increased in SM [median (range) 332.4 (85-3-1913), 3.16 (0.04-27.9) and 4.73 (2.02-27.13)] compared to MSM [99.1 (19.9-767.6), 1.28 (0.03-9.3) and 4.44 (1.19-13.87)], and HCs [48.9 (32.3-88.3), 0.11 (0.02-1.9) and 2.55 (0.73-10.19)]; P<0.001. In SM, GAG-DMMB and GAG-MS were increased in non-survivors (n=3) [median (IQR): 6.72 (3.80-27.87) and 12.15 (7.88-17.20)] compared to survivors n=39 [(3.10 (0.46-4.5) and 4.64 (2.02-15.20)]; P=0.03. Glycocalyx degradation was associated with parasite biomass in MSM (r=0.31, P=0.03 [syndecan-1]; r=0.48 [GAG-DMMB] and r=0.43 [GAG-MS], P<0.001), and SM patients (r=0.29, P=0.04, r=0.47; P=0.002 and r=0.33, P=0.04), and inversely associated with endothelial NO bioavailability. Conclusions Increased endothelial glycocalyx breakdown is associated with impaired vascular NO, severe disease and fatal outcome in adults with falciparum malaria, likely contributing to pathogenesis. Impact of rotavirus vaccine introduction in children less than 2 years of age presenting for medical care with diarrhea in rural Matlab, Bangladesh Abstract Background Following the conclusion of a Rotarix vaccine (HRV) cluster-randomized controlled trial (CRT) in Matlab, Bangladesh, HRV was included in Matlab's routine immunization program. We describe the population-level impact of programmatic rotavirus vaccination in Bangladesh in children <2 years of age Methods Interrupted time series were used to estimate the impact of HRVintroduction. Diarrheal surveillance collected between 2000 and 2014 within the two service delivery areas (icddr,b service area [ISA] and government service area [GSA]) of the Matlab Health and Demographic Surveillance System administered by icddr,b was used. Age-group specific incidence rates were calculated for both rotavirus-positive (RV+) and rotavirus-negative (RV-) diarrhea of any severity presenting to the hospital. Two models were used to assess impact within each service area: Model 1 used the pre-vaccine time period in all villages (HRV- and control-only) and Model 2 combined the pre-vaccine time period and the CRT time period using outcomes from control-only villages. Results Both models demonstrated a downward trend in RV+ diarrheal incidence in the ISA villages during 3.5 years of routine HRV use, though only Model 2 was statistically significant. Significant impact of HRV on RV+ diarrhea incidence in GSA villages was not observed in either model. Differences in population-level impact between the two delivery areas may be due to varied rotavirus vaccine coverage and presentation rate to the hospital. Conclusions This study provides initial evidence of the population-level impact of rotavirus vaccines in children <2 years of age in Matlab, Bangladesh. Further studies of rotavirus vaccine impact after nationwide introduction in Bangladesh are needed. Transmission-blocking effects of primaquine and methylene blue suggest P. falciparum gametocyte sterilisation rather than effects on sex ratio Abstract Gametocyte density and sex-ratio can predict the proportion of mosquitoes that become infected after feeding on blood of patients receiving non-gametocytocidal drugs. Because primaquine and methylene blue sterilize gametocytes before affecting their density and sex-ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects. Principal Controversies in Vaccine Safety in the United States Abstract Concerns about vaccine safety can lead to decreased acceptance of vaccines and resurgence of vaccine-preventable diseases. We summarize the key evidence on some of the main current vaccine safety controversies in the United States, including: 1) MMR vaccine and autism; 2) thimerosal, a mercury-based vaccine preservative, and the risk of neurodevelopmental disorders; 3) vaccine-induced Guillain-Barré Syndrome (GBS); 4) vaccine-induced autoimmune diseases; 5) safety of HPV vaccine; 6) aluminum adjuvant-induced autoimmune diseases and other disorders; and 7) too many vaccines given early in life predisposing children to health and developmental problems. A possible small increased risk of GBS following influenza vaccination has been identified, but the magnitude of the increase is less than the risk of GBS following influenza infection. Otherwise, the biological and epidemiologic evidence does not support any of the reviewed vaccine safety concerns. Insertion as resistance mechanism against integrase inhibitors in several retroviruses Birth Cohort Studies Assessing Norovirus Infection and Immunity in Young Children: A Review Abstract Globally, noroviruses are among the foremost causes of acute diarrheal disease, yet there are many unanswered questions on norovirus immunity, particularly following natural infection in young children during the first 2 years of life when the disease burden is highest. We conducted a literature review on birth cohort studies assessing norovirus infections in children from birth to early childhood. Data on infection, immunity, and risk factors are summarized from 10 community-based birth cohort studies conducted in low- and middle-income countries. Up to 90% of children experienced atleast one norovirus infection and up to 70% experienced norovirus-associated diarrhea, most often affecting children 6 months of age and older. Data from these studies help to fill critical knowledge gaps for vaccine development, yet study design and methodological differences limit comparison between studies, particularly for immunity and risk factors for disease. Considerations for conducting future birth cohort studies on norovirus are discussed. In the Literature Saddle Nose Deformity in an Immunosuppressed Patient Cover News Ebola's Curse: 2013–2016 Outbreak in West Africa By OldstoneMichael and OldstoneMadeleine. Elsevier, 2017. 126 pp. $89.95 (hardcover). ISBN: 9780128138885. Cost-effectiveness and Cost-utility of the Adherence Improving Self-management Strategy in Human Immunodeficiency Virus Care: A Trial-based Economic Evaluation Abstract Background Several promising human immunodeficiency virus (HIV) treatment adherence interventions have been identified, but data about their cost-effectiveness are lacking. This study examines the trial-based cost-effectiveness and cost-utility of the proven-effective Adherence Improving Self-Management Strategy (AIMS), from a societal perspective, with a 15-month time horizon. Methods Treatment-naive and treatment-experienced patients at risk for viral rebound were randomized to treatment as usual (TAU) or AIMS in a multicenter randomized controlled trial in the Netherlands. AIMS is a nurse-led, 1-on-1 self-management intervention incorporating feedback from electronic medication monitors, delivered during routine clinical visits. Main outcomes were costs per reduction in log10 viral load, treatment failure (2 consecutive detectable viral loads), and quality-adjusted life-years (QALYs). Results Two hundred twenty-three patients were randomized. From a societal perspective, AIMS was slightly more expensive than TAU but also more effective, resulting in an incremental cost-effectiveness ratio (ICER) of €549 per reduction in log10 viral load and €1659 per percentage decrease in treatment failure. In terms of QALYs, AIMS resulted in higher costs but more QALYs compared to TAU, which resulted in an ICER of €27759 per QALY gained. From a healthcare perspective, AIMS dominated TAU. Additional sensitivity analyses addressing key limitations of the base case analyses also suggested that AIMS dominates TAU. Conclusions Base case analyses suggests that over a period of 15 months, AIMS may be costlier, but also more effective than TAU. All additional analyses suggest that AIMS is cheaper and more effective than TAU. This trial-based economic evaluation confirms and complements a model-based economic evaluation with a lifetime horizon showing that AIMS is cost-effective. Clinical Trials Registration NCT01429142 First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient Abstract Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus–1 Infection: Week 48 Results of the DRIVE-AHEAD Trial Abstract Background Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile. Methods DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment–naive adults with ≥1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%). Results Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved <50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) (-3.83 vs +13.26 mg/dL) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (−1.6 vs +8.7 mg/dL and −3.8 vs +13.3 mg/dL, respectively). Conclusions In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non–HDL-C compared with EFV/FTC/TDF. Clinical Trials Registration NCT02403674 A 44-Year-Old Female With Overwhelming Sepsis sepsisaspleniaRPSA geneHowell-Jolly bodiesStreptococcus pneumonia Concurrent Seroprevalence of Antibodies to Toxoplasma gondii and Toxocara Species in the United States, 2011–2014 To the Editor—We report supplemental findings incorporating Toxoplasma gondii serology results from our study of risk factors for Toxocara seropositivity in the United States [1] using stored serum samples collected from the National Health and Nutrition Examination Survey (NHANES), 2011–2014. Whereas T. gondii is a protozoan parasite and Toxocara is an intestinal nematode, both share ingestion of contaminated soil as means of exposure in humans. Both parasites can contaminate soil when environmentally resistant T. gondii oocysts or Toxocara cati eggs are shed in the feces of infected cats [2, 3].

Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection Abstract Recognizing the importance of timely guidance regarding the rapidly evolving field of hepatitis C management, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) developed a web-based process for the expeditious formulation and dissemination of evidence-based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance website undergoes periodic updates as necessitated by availability of new therapeutic agents and/or research data. A major update was released electronically in September 2017, prompted primarily by approval of new direct-acting antiviral agents and expansion of the guidance's scope. This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication. The recommendations herein were developed by volunteer hepatology and infectious disease experts representing AASLD and IDSA and have been peer reviewed and approved by each society's governing board.

Functional Improvements Utilizing the Short Physical Performance Battery (SPPB) in the Elderly after Epidural Steroid Injections

Abstract

Purpose of Review

The treatment of debilitating pain and loss of function secondary to lumbar stenosis is in high demand with the aging patient population. Options, including epidural steroid injections (ESIs) and medication therapy, are limited and it is unclear if they provide any functional improvements. In this prospective study, we evaluate functional outcomes in older adults with symptomatic lumbar stenosis treated with ESIs compared to those managed with medications by introducing the Short Physical Performance Battery (SPPB). Our study was IRB-approved and included 16 patients, 68 to 83 years old, with symptomatic back and radicular leg pain secondary to lumbar stenosis. Patients could elect to undergo a lumbar ESI (n = 11) or be treated via medication management (n = 5). Numeric pain score, SPPB score, and adverse events were measured and compared at baseline and a 1-month follow-up visit.

Recent Findings

Statistically significant improvements were observed from baseline compared to the 1-month follow-up for total SPPB score in the injection group. Similar improvements in the injection group were observed for pain scores and the SPPB subcomponents such as the 4-m walk test, chair stand time, and balance score. Comparatively, no statistically significant improvements were observed in the medication group.

Summary

Lumbar ESIs improved objective physical capacity parameters and pain scores in elderly patients with symptomatic lumbar stenosis compared to medication management. In addition, the SPPB is an easy-to-use tool to measure changes in physical function in older adults and could easily be integrated into an outpatient pain clinic.

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Perioperative Considerations in the Management of Anticoagulation Therapy for Patients Undergoing Surgery

Abstract

Purpose of Review

As ambulatory surgery has become increasingly more common, the appropriate management of anticoagulation therapy in patients undergoing invasive procedures has become progressively more relevant to healthcare professionals. The purpose of this literature review is to provide an overview of current common anaticoagulants and their pharmacological properties and to evaluate recent relevant literature and bridging therapy and provide recommendations on risk-guided therapy.

Recent Findings

With the development of new drugs and the advancing study and practice of anticoagulation use, clinicians must keep up-to-date on the optimal management of patients requiring anticoagulation. NOACs and warfarin continue to be the mainstays of treatment, with varying timelines regarding when to hold administration of the different agents within the perioperative period.

Summary

There are numerous factors that are considered in patients with multiple comorbidities including the risk for stroke on long-term anticoagulation and risk for thromboembolism, particularly in the perioperative setting when certain medication regimens may be altered and/or briefly held. There is ongoing investigation whether certain NOACs have more efficacy or greater safety profiles, depending on the degree of surgical intervention.

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Surgery is not the only determinant of an outcome in patients with hypopharyngeal carcinoma

Abstract

Background

The aim of this study was to evaluate the outcomes in patients treated for hypopharyngeal carcinoma in a single‐center and the importance of considering how patient factors influence outcomes.

Methods

A retrospective review was conducted on patients who were seen at the Prince of Wales Hospital from 1968 to 2015. Kaplan‐Meier and Cox regression analyses were performed for each patient and treatment factor to investigate outcomes of local control, cancer‐specific survival (CSS), and ultimate local control.

Results

Three hundred thirty patients were analyzed. Significant multivariate predictors for improved local control and CSS were fitness for surgery, cancer operability, surgery with adjuvant radiotherapy, no treatment interruptions (P < .05). Five‐year local control (84%), CSS (50%), and ultimate local control (84%) rates were significantly higher in patients treated surgically with adjuvant radiotherapy, compared to single modality treatment (P < .05).

Conclusion

Patient factors influence the outcomes experienced by patients with hypopharyngeal carcinoma.

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Spindle cell liposarcoma with a TRIO-TERT fusion transcript

Abstract

Conventional well-differentiated, dedifferentiated, and myxoid liposarcomas have long been known to harbor numerous typical genetic alterations that allow for diagnosis of these tumors. These include MDM2 and CDK4 amplification in well-differentiated and dedifferentiated liposarcomas as well as FUS-DDIT3 rearrangements in myxoid liposarcoma. More recently, in-frame TRIO-TERT fusion genes have been described in a subset of non-translocation-related sarcomas including myxofibrosarcoma, dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, pleomorphic rhabdomyosarcoma, and leiomyosarcoma. These genetic rearrangements lead to TERT mRNA expression levels hundreds of times higher than normal, causing increased telomerase activation in these tumors. Herein, we describe an unusual case of a liposarcoma with spindle cell features and a TRIO-TERT fusion transcript identified through next-generation sequencing.

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Whatever Happened to Local Otolaryngology Societies?

This essay describes the importance of, and decline of membership in, specialty medical societies.

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An Indolent Middle Ear Mass

A woman in her 30s with a 1-year history of left ear fullness presented with left-sided hearing that improved temporarily with autoinsufflation. What is your diagnosis?

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February Issue Highlights

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Publication Bias and Systematic Reviews in Top-Ranked Otolaryngology Journals

This study analyzes whether 324 systematic reviews that contain at least 1 meta-analysis with 10 or more primary studies published in top otolaryngology journals that do not evaluate for publication bias show evidence of such bias.

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Error in Figure Labels

In the article titled "Is It Time to Rethink the Approach to Internal Nasal Valve Stenosis?," the 2 Figure labels (a and b) were transposed so that the labels corresponded to the incorrect descriptions in the Figure caption. The Figure has been corrected online.

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Association of Treatment Delays With Survival for Patients With Head and Neck Cancer

This systematic review synthesizes information about the association between delays in the delivery of care for head and neck cancer and oncologic outcomes.

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Labels Reversed in Figure 1

In the Original Investigation titled "Association of Adjuvant Radiation Therapy With Survival in Patients With Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck" by Harris et al, the labels in Figure 1 were reversed. This article has been corrected online.

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Pretreatment Hearing Level—Another Prognostic Factor in Sudden Sensorineural Hearing Loss—Reply

In Reply We thank Dr Wu and colleagues for their interest and comments on our research. Various factors may affect hearing recovery after SSHL, such as age, degree of hearing loss, type of hearing loss, interval from onset of symptoms to treatment, tinnitus, type 2 diabetes, cardiovascular disease, and the presence of vertigo. We were unable to include the hearing level at onset into our analyses owing to the lack of corresponding data in the included studies. Moreover, only 1 of the included studies assessed the possible association between the presence of vertigo and hearing recovery in patients with severe sudden sensorineural hearing loss (≥60 dB). We also think that the opinion by Dr Wu et al that the presence of vertigo is significantly correlated only with hearing recovery in the group with profound SSHL may have implications for the understanding of the mechanisms of SSHL with vertigo, but we were unable to retrieve the raw data. At present, the pathogenesis, clinical manifestations, optimal treatments, and prognostic factors of SSHL are not clear. We are in the process of validating the occurrence of vertigo and its possible role in SSHL. A complete analysis of this role will require more unbiased studies with prospectively gathered data in a large sample size to estimate the precise association of vertigo with the clinical manifestation and prognosis of SSHL.

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Traumatic Lower Lip Myiasis

This is the report of a case of a homeless man in his 50s who presented with traumatic lower lip myiasis.

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Anemia and 30-Day Morbidity and Mortality After Thyroidectomy in Thyroid Cancer Treatment

This cross-sectional cohort study uses the American College of Surgeons National Surgical Quality Improvement Program database to evaluate whether an association exists between preoperative anemia and postoperative 30-day morbidity and mortality outcomes following thyroidectomy in adult patients with thyroid cancer.

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Aspiration in Infants With Laryngomalacia and Respiratory and Feeding Difficulties

This study evaluates the medical records of infants with laryngomalacia and associated breathing and feeding difficulties to determine the prevalence of aspiration among this pediatric patient population.

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Secondary Endolymphatic Hydrops Associated With Spontaneous Intracranial Hypotension

This case report describes a woman in her 40s who presented with spontaneous intracranial hypotension associated with cerebrospinal fluid leakage.

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Silent Aspiration in Laryngomalacia?

Laryngomalacia is the most common laryngeal anomaly in infants, with a presentation of inspiratory stridor being nearly ubiquitous. In addition, young children with laryngomalacia can demonstrate feeding difficulty, dysphagia, aspiration, failure to thrive, apnea, cyanosis, and/or obstructive sleep apnea. Managing the balancing act between sucking, breathing, and swallowing is anticipated to carry additional challenge in infants with airway abnormalities, potentially leading to dysphagia, aspiration, and feeding difficulties. Somewhat unsurprisingly, infants with laryngomalacia may cough and choke during feeding, take their feeds slowly, or develop a worsening of their stridor during feeding. The association between laryngomalacia and feeding disorders is further strengthened by a biological gradient relationship, with more severe laryngomalacia cases shown to be more likely to have symptoms of feeding difficulty. In addition to dyscoordination, other proposed causes for feeding challenges in patients with laryngomalacia include decreased laryngeal sensation secondary to acid reflux and an alteration in the sensorimotor integrative function of the larynx. The association between acid reflux and laryngomalacia is well established, although evidence is lacking for causality or even direction of causality (ie, which is the chicken and which is the egg). Sensorimotor impairment in laryngomalacia is evidenced by the finding that children with laryngomalacia have higher rates of neurologic abnormalities such as hypotonia, central apneas and developmental disorders, and histopathologic nerve differences in their laryngeal mucosa.

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JAMA Otolaryngology–Head & Neck Surgery

Mission Statement:JAMA Otolaryngology–Head & Neck Surgery provides timely information for physicians and scientists concerned with diseases of the head and neck. Given the diversity of structure and function based in this anatomic region, JAMA Otolaryngology–Head & Neck Surgery publishes clinical, translational, and population health research from an array of disciplines. We place a high priority on strong study designs that accurately identify etiologies, evaluate diagnostic strategies, and distinguish among treatment options and outcomes. Our objectives are to (1) publish original contributions that will enhance the clinician's understanding of otolaryngologic disorders, benefit the care of our patients, and stimulate research in our field; (2) forecast important advances within otolaryngology—head and neck surgery, particularly as they relate to the prevention, diagnosis, and treatment of disease through clinical and translational research, including that of the human genome and novel imaging techniques; (3) address questions of clinical outcomes and cost-effectiveness that result from clinical intervention, which grow in importance as health care providers are increasingly challenged to provide evidence of enhanced survival and quality of life; (4) provide expert reviews of topics that keep our readers current with true advances and also to provide a valuable educational resource for trainees in the several disciplines that treat patients with diseases of the head and neck; (5) serve as a forum for the concerns of otolaryngologists such as socioeconomic, legal, ethical, and medical issues; (6) provide helpful critiques that enable contributing authors to improve their submissions. We encourage a concise presentation of information and employ an abstract format that efficiently assesses validity and relevance from a clinical perspective. This approach promotes succinct yet complete presentation for our readers and electronic information resources. We believe this approach typifies the commitment of JAMA Otolaryngology–Head & Neck Surgery to providing important information that is easily interpreted by its diverse readership.

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Drug-Induced Sleep Endoscopy Findings in Supine vs Nonsupine Body Positions in Obstructive Sleep Apnea

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The International Society of Urological Pathology Education web—a web-based system for training and testing of pathologists

Abstract

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Sponsors:   Xencor, Inc.;   ICON plc
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Recruiting

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Pneumocephalus and pneumoventricle

CASE REPORT

Year : 2019  |  Volume : 14  |  Issue : 1  |  Page : 325-328

Delayed pneumoventricle following endonasal cerebrospinal fluid rhinorrhea repair with thecoperitoneal shunt

Shyam Sundar Krishnan, Adarsh Manuel, Madabhushi Chakravarthy Vasudevan
Department of Neurosurgery, Achanta Lakshmipathi Neurosurgical Centre, Voluntary Health Services Hospital, Chennai, Tamil Nadu, India

Date of Web Publication

21-Feb-2019

Correspondence Address:
Dr. Shyam Sundar Krishnan
Department of Neurosurgery, Achantha Lakshmipathy Neurosurgical Centre, Voluntary Health Services, TTTI Post, Taramani, Chennai - 600 113, Tamil Nadu 
India

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/ajns.AJNS_224_18

Abstract

Pneumocephalus and pneumoventricle are well-documented in neurosurgical practice. Although both are common posttraumatic sequelae, iatrogenic causes are also well recognized. Iatrogenic causes may be seen after intracranial surgical procedures or cerebrospinal fluid (CSF) diversion procedures. Small amount of pneumoventricle postshunt procedure is usually a self-limiting condition. Rarely, the patient may develop tension pneumoventricle which requires emergency intervention. The occurrence of delayed tension pneumoventricle/pneumatocele following surgery for CSF rhinorrhea with CSF diversion procedures is very rare. We report one case of late presentation of delayed tension pneumoventricle with temporal pneumatocele in a patient who underwent transnasal endoscopic repair of CSF fistula followed by thecoperitoneal shunt. This condition is potentially lethal that requires prompt recognition and surgical treatment.

Keywords: Cerebrospinal fluid rhinorrhea, pneumatocele, pneumocephalus, tension pneumoventricle, thecoperitoneal shunt

How to cite this article: Krishnan SS, Manuel A, Vasudevan MC. Delayed pneumoventricle following endonasal cerebrospinal fluid rhinorrhea repair with thecoperitoneal shunt. Asian J Neurosurg 2019;14:325-8

How to cite this URL: Krishnan SS, Manuel A, Vasudevan MC. Delayed pneumoventricle following endonasal cerebrospinal fluid rhinorrhea repair with thecoperitoneal shunt. Asian J Neurosurg [serial online] 2019 [cited 2019 Feb 21];14:325-8. Available from: http://www.asianjns.org/text.asp?2019/14/1/325/250010

Introduction

The occurrence of pneumoventricle as a delayed complication of cerebrospinal fluid (CSF), rhinorrhea repair with thecoperitoneal shunt is a rare presentation. Tension pneumocephalus is a known and common entity as compared to tension pneumoventricle. The presence of pneumatocele in the temporal lobe in association with the above condition makes it a unique clinical presentation.

Case Report

This 48-year-old female presented with complaints of CSF rhinorrhea since 2 months. There was no history or clinical finding suggestive of trauma or meningitis. Her neurological examination otherwise was unremarkable. Computed tomography (CT) face/skull base followed by magnetic resonance imaging (MRI) brain and diagnostic nasal endoscopy were done which showed the defect in the cribriform plate and left a lateral wall of the sphenoid sinus [Figure 1]. Lumbar puncture done showed the CSF opening pressure of 35 cm of water and no evidence of infection.

Figure 1: Magnetic resonance images of the patient showing cerebrospinal fluid fistula in cribriform plate (short arrow) and lateral wall of sphenoid sinus (long arrow) and computed tomography paranasal sinuses bone window showing defect (long arrow) in the sphenoid bone with cerebrospinal fluid filling into the left sphenoid sinus (long arrow) Click here to view

She underwent transnasal endoscopic repair of CSF fistula along with placement of thecoperitoneal shunt with no anti-siphon device. The bath-plug technique was used to seal the defects by introducing a fat plug with a specifically secured vicryl suture into the intradural space, followed by applying traction on the suture to seal the defect much like a bathplug seals a bath. Rectus abdominis fascia graft was harvested from the same abdominal wound used for shunt placement. The defect was further reinforced by fascia, fat and surgical, and fibrin sealant. It was decided to place thecoperitoneal shunt as the CSF opening pressure was very high to prevent the recurrent CSF leak. Postoperatively, she was symptom-free and discharged to home.

After 1 month, she presented with memory disturbances, multiple episodes of vomiting and headache. There was no recurrence of CSF rhinorrhea or postnasal drip. MRI brain showed pneumoventricle with right temporal pneumatocele [Figure 2]. Diagnostic endoscopy was done which showed dislodged fascia graft. She underwent emergency repacking of the CSF fistula with the removal of thecoperitoneal shunt and aspiration of pneumoventricle underwater seal which was under high pressure. Fasica graft was repositioned to cover the defect after sealing it with fat using the bath-plug technique as in the previous surgery. Fat and fascia packing was reinforced with a pedicled Hadad flap and fibrin sealant. She improved in her symptoms postoperatively. Postoperative CT brain showed good resolution of pneumoventricle with reduced size of ventricular system [Figure 3]. She remained symptom free at 6-month follow-up.

Figure 2: Magnetic resonance imaging brain showing pneumatocele (long arrow) in the right temporal lobe and pneumoventricle (short arrow) Click here to view

Figure 3: Postoperative computed tomography brain showing good resolution of tension pneumoventricle and right temporal pneumatocele Click here to view

Discussion

Pneumocephalus is defined as the presence of air in the intracranial compartment due to communication between intracranial and extracranial compartments.^[1],[2],[3] Tension pneumocephalus is a rarer form of pneumocephalus in which the air is under high pressure.^{[1],[2],[4],[5],[6],[7]}Pneumocephalus occur most commonly in head injuries.^[1],[2],[3] Intra- and post-operative pneumocephalus/pneumoventricle is well-documented, especially, in sitting position surgeries, nitrous oxide anesthesia, and CSF diversion surgeries.^[1],[2],[3] Other conditions causing pneumocephalus are CNS infections caused by gas-producing organisms, congenital neurenteric cysts, and postradiotherapy for nasopharyngeal carcinoma.^{[1],[2],[4],[5],[6],[7]} Small amounts of pneumoventricle alone are common after shunt surgeries, ventricular tumor surgeries.^{[1],[2],[3],[8]} Sometimes, wound breakdown following the shunt surgeries may cause influx of air peritubally and cause pneumoventricle.^[9] Delayed tension pneumoventricle is an extremely rare complication and <50 cases have been described in the literature.^[1]Pneumocephalus/pneumoventricle is usually benign which does not require any treatment, and it decreases at a rate of 25% per week.^{[4],[9],[10],[11],[12]}

Two different mechanisms have been proposed in the development of delayed tension pneumoventricle/pneumocephalus.^{[1],[2],[3],[13],[14]}

1. Dandy's theory of ball valve mechanism: one-way ball valve mechanism causing air to flow into the skull through dural defect where the exit is prevented by brain or meninges sealing the leak site
2. Horowitz inverted soda-bottle effect: negative pressure develops inside the cranial cavity as a result of excessive loss of CSF. This drop in intracranial pressure (ICP) causes air to flow from the extra to the intracranial space across the pressure gradient.

In our case, the patient presented with spontaneous CSF rhinorrhea and was treated by endoscopic skull base defect repair with thecoperitoneal shunt placement. CSF rhinorrhea can be due to traumatic or nontraumatic causes. Traumatic can be either due to head injuries causing skull base fractures or due to iatrogenic causes. Spontaneous leaks could be associated with or without raised ICP. High-pressure leaks could account up to 45% of the nontraumatic CSF rhinorrhea.^[15] Sustained increase in ICP causes bony erosion and creation of an osteodural defect in pneumatized parts of the skull base such as cribriform plate, craniopharyngeal canal, sella, and spheno-occipital synchondrosis leading to CSF leak.^[7],[15] CSF leaks in these cases have been postulated to represent a manifestation of benign intracranial hypertension or pseudotumor cerebri.^{[16],[17],[18],[19]} In our case also CSF leak was associated with raised ICP with no evidence of trauma or infection. This could be an underlying benign ICP with or without congenital defect.

Normal pressure leaks represent 55% of the nontraumatic cases of the CSF rhinorrhea.^[20],[21] It is hypothesized that the spontaneous leak is due to point erosions in the skull base which occur in normal person as a result of physiologic alterations in CSF pressure with transient increase in ICP up to 80 mm of water lasting for few seconds.^[15] Other nontraumatic causes of CSF leak include congenital skull base defects, erosion of the skull base by tumors, infection, mucocele, and following radiation.

CSF diversion in patients with long-standing raised ICP may result in the pneumoventricle by air aspiration through a preexisting congenital or iatrogenic skull base erosion/fistula.^[3] These fistulous sites/erosion points are plugged by scarred meninges or gliotic brain which open up due to a drop in ICP causing inward flow of air. This air is prevented from escaping by temporarily resealing of meningeal cicatrix and this cycle repeatedly happens, resulting in tension pneumoventricle (ball valve mechanism). Shunts by their siphon effect can create significant negative ICP drop which ranges from −30 to −155 mm of water, and sometimes as low as −440 mm of water.^[2],[5] Pneumatocele is located close to the site of fistulae and more common in the temporal lobe. In our case also there might have been a sustained negative pressure caused by the thecoperitoneal shunt without anti-siphon device.

Pneumoventricle presents usually with symptoms and signs of raised ICP such as a recurrent headache with vomiting, impairment of consciousness, seizures, memory disturbances, and gait disturbance. Sometimes, patients present with acute or chronic meningitis. Intracranial splashing sounds called "bruit hydroaerique" are characteristic in some patients. Similarly, our patient also presented with memory disturbances and cognitive impairment during the second presentation.

The delay from CSF shunting to the development of pneumocephalus may vary from a week up to 5 years.^[7],[22] The usage of high-pressure shunts and antisiphon devices have been recommended by some authors to prevent this complication.^[1],[2],[23] Our routine policy is to place Chhabra standard adult thecoperitoneal shunt with no anti-siphon device. However, anti-siphon device has advantages of preventing over-drainage of CSF, and the reservoir gives access to check the patency of the shunt system. We have seen an increased risk of shunt obstruction with anti-siphon device. We had 42 cases who underwent Lumbar-peritoneal (LP) shunts without anti-siphon device in the past 5 years and none of them presented with shunt obstruction or shunt-related morbidity other than shunt migration (five patients) and abdominal pseudocyst (two patients). Programmable shunt provides the benefit of adjusting the pressure setting according to the ventricular pressure. We routinely do not use programmable LP shunts as ours is a resource-limited center with most of the patients coming from low-socioeconomic strata.

Prevention of infection, treatment of raised ICP, aspiration of pneumoventricle, closure of fistula, and removal of shunt tube are the keys to successful management of tension pneumoventricle secondary to CSF fistula.^[23] Broad-spectrum antibiotics are used after shunt removal, but its prophylactic usage is debated.^[1],[5],[23] Removal of the shunt tube relieves the sustained negative pressure which may cause recurrent pneumoventricle/pneumocephalus. Postshunt removal a temporary CSF diversion is preferred by some authors, especially, if the infection is doubted clinically or confirmed.^[1],[2],[23]

In our case, as there was dislodgement of fat-fascia graft, repacking was done followed by aspiration of pneumoventricle underwater seal and thecoperitoneal shunt was removed. We feel the tension pneumoventricle caused air to dissect into the right temporal lobe region under pressure forming the temporal pneumatocele. The shunt was removed to alleviate negative pressure gradient as it was nonprogrammable shunt with no anti-siphon device. The patient had complete resolution of symptoms after the procedure. This makes us think that we should probably reconsider the usage of anti-siphon device and also a pedicled flap to repair the skull base defects. A programmable valve may be the best choice in financially affordable patients. In patients with normal/moderately high ICP (25 cm of water), a temporary lumbar drain can be considered for few days until the defects heal thus preventing the recurrent CSF leaks.

Conclusion

Although it is a rare entity, tension pneumoventricle should be considered in patients who have undergone CSF diversion procedures along with anterior skull base repair. Sometimes, it can occur as a delayed complication which may lead to acute neurological deterioration and sudden death. Hence, prompt diagnosis is necessary for timely intervention and prevention.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 

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Figures

  [Figure 1], [Figure 2], [Figure 3]