bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical Illness-Related Corticosteroid Insufficiency (CIRCI): A Narrative Review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)
Authors: Annane Djillali , Pastores Stephen M. , Arlt Wiebke , Balk Robert A. , Beishuizen Albertus , Briegel Josef , Carcillo Joseph , Christ-Crain Mirjam , Cooper Mark S. , Marik Paul E. , Meduri Gianfranco Umberto , Olsen Keith M. , Rochwerg Bram , Rodgers Sophia C. , Russell James A. , Van den Berghe Greet
Published: September 2017

Objective:

To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI).

Participants:

A multi-specialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.

Data Sources:

Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews.

Results:

Three major pathophysiologic events were considered to constitute CIRCI: dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids. The dysregulation of the HPA axis is complex, involving multidirectional crosstalk between the CRH/ACTH pathways, autonomic nervous system, vasopressinergic system, and immune system. Recent studies have demonstrated that plasma clearance of cortisol is markedly reduced during critical illness, explained by suppressed expression and activity of the primary cortisol-metabolizing enzymes in the liver and kidney. Despite the elevated cortisol levels during critical illness, tissue resistance to glucocorticoids is believed to occur due to insufficient glucocorticoid alpha-mediated anti-inflammatory activity.

Conclusions:

Novel insights into the pathophysiology of CIRCI add to the limitations of the current diagnostic tools to identify at-risk patients and may also impact how corticosteroids are used in patients with CIRCI.
Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017
Authors: Annane Djillali , Pastores Stephen M. , Rochwerg Bram , Arlt Wiebke , Balk Robert A. , Beishuizen Albertus , Briegel Josef , Carcillo Joseph , Christ-Crain Mirjam , Cooper Mark S. , Marik Paul E. , Umberto Meduri Gianfranco , Olsen Keith M. , Rodgers Sophia C. , Russell James A. , Van den Berghe Greet
Published: September 2017

Objective:

To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients.

Participants:

A multispecialty task force of 16 international experts in critical care medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine.

Design/Methods:

The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members.

Results:

The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of < 9 μg/dL) after cosyntropin (250 μg) administration and a random plasma cortisol of < 10 μg/dL may be used by clinicians. We suggest against using plasma-free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using IV hydrocortisone < 400 mg/day for ≥ 3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO2 < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence).

Conclusions:

Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.
Use of Google Trends to Examine Interest in Mohs Micrographic Surgery: 2004 to 2016
Authors: Callaghan Daniel J.
Published: September 2017

BACKGROUND

Mohs micrographic surgery (MMS) is the gold standard for treatment of high-risk skin cancers. There has been an upward trend in the use of this procedure as demonstrated by data from Medicare and the National Ambulatory Medical Care Survey.

OBJECTIVE

To assess interest in MMS among members of the general public as measured by number of online searches, and how that interest has changed over time.

MATERIALS AND METHODS

Google Trends was used to plot interest in search terms including “Mohs surgery,” “basal cell carcinoma,” “squamous cell carcinoma,” “melanoma,” and “skin cancer” from January 1, 2004, to November 30, 2016.

RESULTS

Search interest for the term “Mohs surgery” has steadily increased since 2004 and correlates closely with increased interest for “basal cell carcinoma” (r = 0.82) and “squamous cell carcinoma” (r = 0.85). Search interest in MMS did not correlate well with searches for melanoma (r = −0.15) or skin cancer (r = −0.29).

CONCLUSION

Public interest in MMS has continued to steadily increase in the United States, which may be a reflection of the increasing volume of MMS that is performed.
Photography in Dermatologic Surgery: Selection of an Appropriate Lighting Solution for a Particular Clinical Application
Authors: Chen Brian R. , Poon Emily , Alam Murad
Published: September 2017

BACKGROUND

Lighting is an important component of consistent, high-quality dermatologic photography. There are different types of lighting solutions available.

OBJECTIVE

To evaluate currently available lighting equipment and methods suitable for procedural dermatology.

MATERIALS AND METHODS

Overhead lighting, built-in camera flashes, external flash units, studio strobes, and light-emitting diode (LED) light panels were evaluated with regard to their utility for dermatologic surgeons. A set of ideal lighting characteristics was used to examine the capabilities and limitations of each type of lighting solution. Recommendations regarding lighting solutions and optimal usage configurations were made in terms of the context of the clinical environment and the purpose of the image.

RESULTS

Overhead lighting may be a convenient option for general documentation. An on-camera lighting solution using a built-in camera flash or a camera-mounted external flash unit provides portability and consistent lighting with minimal training. An off-camera lighting solution with studio strobes, external flash units, or LED light panels provides versatility and even lighting with minimal shadows and glare.

CONCLUSION

The selection of an optimal lighting solution is contingent on practical considerations and the purpose of the image.
Hepatic Legionella pneumophila Infection in an Infant With Severe Combined Immunodeficiency
Authors: Lapidot Rotem , Alawdah Laila , Köhler J. R. , Paulson Vera , Levy Ofer
Published: September 2017

Rare cases of extrapulmonary involvement in Legionella spp. infections have been described, mostly in immunocompromised adults. We report a case of a 2-month old male with reticular dysgenesis variant of severe combined immune deficiency with multiple liver lesions. Core-needle biopsies of one liver lesion demonstrated Gram-negative bacilli and a broad-spectrum polymerase chain reaction assay detected Legionella pneumophila.
Chronic Q Fever Infections in Israeli Children
Authors: Sachs Nimrod , Atiya-Nasagi Yafit , Beth-Din Adi , Levy Itzhak , Ben-Shimol Shalom , Tasher Diana , Grisaru-Soen Galia , Dabaja Haleema , Kassis Imad , Spilman Shiri , Bilavsky Efraim
Published: September 2017

Background:

Q fever is a zoonosis caused by the bacterium Coxiella burnetii (C. burnetii) with a worldwide distribution. Our aim was to assess the epidemiology, clinical manifestations and treatment regimens of chronic Q fever infections in Israeli children during the past 25 years.

Methods:

Cases were collected from the national Q fever reference laboratory database. Demographic, epidemiologic and clinical data were reviewed using a structured questionnaire sent to the referring physician. Cases were defined according to the new Dutch Consensus Guidelines.

Results:

A total of 16 children originating from all regions of the country were found positive for chronic Q fever infections. The most common infection site was bone or joint (8/16, 50%), all in previously healthy children. Endovascular infections were found in 5 children (31%), all with an antecedent cardiac graft insertion. According to the new Consensus Guidelines, 9 children (56%) had a proven infection, 3 (19%) a probable infection and 4 (25%) a possible chronic Q fever infection. Almost all cases were treated with a long-term antibiotic regimen, often necessitating a change in medication because of persistent or rising titers.

Conclusions:

Although pediatric chronic Q fever infections are rare, incidence has been rising. The most common infection site was bone or joint. A high index of suspicion is necessary, even in cases of previously healthy children without a possible exposure history. Use of the relatively new diagnostic tools in combination with serologic methods is helpful in diagnosing proven cases. There is no consensus as to the selection or duration of antibiotic treatment.
Inpatient Treatment of Patients Admitted for Dizziness: A Population-Based Healthcare Research Study on Epidemiology, Diagnosis, Treatment, and Outcome
Authors: Renner Vera , Geißler Katharina , Boeger Daniel , Buentzel Jens , Esser Dirk , Hoffmann Kerstin , Jecker Peter , Mueller Andreas , Radtke Gerald , Axer Hubertus , Guntinas-Lichius Orlando
Published: September 2017

Objective:

To determine inpatient treatment rates of patients with dizziness with focus on diagnostics, treatment and outcome.

Study Design:

Retrospective population-based study.

Setting:

Inpatients in the federal state Thuringia in 2014.

Patients:

All 1,262 inpatients (62% females, median age: 61 yr) treated for inpatient dizziness were included.

Main Outcome Measures:

The association between analyzed parameters and probability of improvement and recovery was tested using univariable and multivariable statistics.

Results:

Final diagnosis at demission was peripheral vestibular disorder (PVD), central vestibular disorder (CVD), cardiovascular syndrome, somatoform syndrome, and unclassified disease in 75, 9, 3, 0.6, and 13%, respectively. The most frequent diseases were acute vestibular neuritis (28%) and benign paroxysmal positional vertigo (22%). The follow-up time was 38 ± 98 days. 88.5% of patients showed at least an improvement of complaints and 31.4% a complete recovery. The probability for no improvement from inpatient dizziness was higher if the patient had a history of ear/vestibular disease (hazard ratio [HR] = 1.506; 95% confidence interval [CI] = 1.301–1.742), and was taking more than two drugs for comorbidity (HR = 1.163; CI = 1.032–1.310). Compared with final diagnosis of cardiovascular syndrome, patients with PVD (HR = 1.715; CI = 1.219–2.415) and CVD (HR = 1.587; CI = 1.076–2.341) had a worse outcome.

Conclusions:

Inpatient treatment of dizziness was highly variable in daily practice. The population-based recovery rate was worse than reported in clinical trials. We need better ways to implement clinical trial findings for inpatients with dizziness.
Integration of Contact Tracing and Phylogenetics in an Investigation of Acute HIV Infection
Authors: Dennis Ann M. , Pasquale Dana K. , Billock Rachael , Beagle Steve , Mobley Victoria , Cope Anna , Kuruc JoAnn , Sebastian Joseph , Walworth Charles , Leone Peter A.
Published: September 2017

Background

The integration of traditional contact tracing with HIV sequence analyses offers opportunities to mitigate some of the barriers to effective network construction. We used combined analyses during an outbreak investigation of spatiotemporally clustered acute HIV infections to evaluate if the observed clustering was the product of a single outbreak.

Methods

We investigated acute and recent HIV index cases reported in North Carolina from 2013 to 2014 and their reported contacts. Contact tracing networks were constructed with surveillance data and compared with phylogenetic transmission clusters involving an index case using available HIV-1 pol sequences including 1672 references. Clusters were defined as clades of 2 or more sequences with a less than 1.5% genetic distance and a bootstrap of at least 98% on maximum-likelihood phylogenies.

Results

In total, 68 index cases and 210 contacts (71 HIV infected) were reported. The contact tracing network involved 58 components with low overall density (1.2% statewide); 33% of first-degree contacts could not be located. Among 38 (56%) of 68 index cases and 34 (48%) of 71 contacts with sequences, 13 phylogenetic clusters were identified (size 2–4 members). Four clusters connected network components that were not linked in contact tracing. The largest component (n = 28 cases) included 2 distinct phylogenetic clusters and spanned 2 regions.

Conclusions

We identified the concurrent expansion of multiple small transmission clusters rather than a single outbreak in a largely disconnected contact tracing network. Integration of phylogenetic analyses provided timely information on transmission networks during the investigation. Our findings highlight the potential of combined methods to better identify high-risk networks for intervention.
Prognostic Value of Type D Personality for In-stent Restenosis in Coronary Artery Disease Patients Treated With Drug-Eluting Stent
Authors: Wang Yini , Liu Guojie , Gao Xueqin , Zhao Zhenjuan , Li Ling , Chen Wei , Tao Hui , Yu Bo , Lin Ping
Published: September 2017

Objective

To evaluate the predictive value of Type D personality on in-stent restenosis (ISR) rates at 1 and 2 years post–percutaneous coronary intervention (PCI) in patients with coronary artery disease.

Methods

Consecutive patients with coronary artery disease who underwent PCI for drug-eluting stents (n = 173) completed the Type D Scale-14 (DS14) at baseline. Follow-up coronary angiographic evaluation was routinely planned at 1 and 2 years after the procedure.

Results

Follow-up coronary angiography was performed in 159 and 112 patients at 1 and 2 years post-PCI, respectively. On multivariate analysis, Type D personality was found to be an independent predictor of ISR at 1 year (odds ratio [OR] = 2.67, 95% confidence interval [CI] = 1.16–6.14, p = .021) and 2 years (OR = 4.92, 95% CI = 1.82–9.60, p = .017) after adjusting for cardiovascular risk factors. However, Type D did not predict ISR when the analysis was performed using the interaction between negative affectivity and social inhibition. The main effect of negative affectivity emerged as a significant risk factor for 1-years (OR = 4.22, 95% CI = 1.18–7.86, p = .034) and 2-year ISR (OR = 6.93, 95% CI = 2.25–11.50, p = .016).

Conclusions

In this study, Type D personality was an independent predictor of ISR at 1 and 2 years post-PCI; the association strengthened with time. The negative affectivity component seems to drive the relationship between Type D and ISR over time. Our findings provide new insights into the mechanisms involved in the association between Type D and adverse clinical outcomes of PCI.
A Novel Three-Step Method for Correction of Type 1 Stahl Ear
Authors: Borrelli Mimi R. , Davidson Edward H. , Kumar Anand R.
Published: September 2017

Background:

Stahl ear, a rare congenital auricular anomaly, occurs when a third crus crosses the scaphoid fossa. Optimal elimination of the third crus and reconstruction the superior crus in type 1 Stahl ear remain undercharacterized. We present a novel 3-step technique to reliably correct a type 1 Stahl ear as a case report.

Methods:

A 10-year-old male with bilateral prominent type 1 Stahl ears is presented. An anterior curvilinear helical fold incision and posterior V wedge excision was used for exposure. Step 1, the third crus cartilage was excised as a full-thickness wedge and the gap approximated with posteriorly everting horizontal mattress sutures to create a flattened scaphoid fossa. Step 2, the superior crus was created using anteriorly placed horizontal mattress sutures for direct shaping. Step 3, the skin was redraped without excess trimming to minimize the visible scar.

Results:

The 3-step approach effectively eliminated the third crura and recreated the superior crura of the type 1 Stahl ears, and resulted in minimal visible anterior scarring.

Discussion:

The anterior approach provided excellent visualization and permitted tactical suture placement. The wedge excisions successfully removed the third crura. The horizontal mattress sutures to flatten the scaphoid fossa, enhance the natural antihelical curves, and form the superior crura were simple and effective.
Postoperative Changes in Isolated Medial Orbital Wall Fractures Based on Computed Tomography
Authors: Jung Soyeon , Lee Jang Won , Kim Chung Hun , Hwang Euna , Lim Hyoseob , Jung Sung Won , Koh Sung Hoon
Published: September 2017

The treatment has been improved on the accurate reduction of blow-out fracture for many decades. But still, it has been limited to reduce completely when surgeons are approaching by conventional technique. The authors analyzed the postoperative results using computed tomography (CT) scans after conventional open reduction of isolated medial wall fracture. Thirty-seven patients with isolated medial wall fracture were reviewed. All patients underwent preoperative, immediate, and postoperative CT scans. Two surgeons have performed the surgery by conventional open reduction with transcaruncular approach and absorbable mesh insertion. The authors evaluated changing orbital volume and distance, comparing the immediate and 6 months postoperative outcomes with preoperative outcome. The differences between immediate postoperative and 6 months postoperatively data were statistically evaluated. The authors used the distant value to minimize bias of CT view selection. Significant differences from the 2 kinds of data were observed (P < 0.05 for volume, P < 0.01 for distance, Paired t test). Bone remodeling process after conventional open reduction of orbital wall has not been fully understood. Most popular technique is conventional open reduction and mesh insertion but it is not easy for surgeons to reduce fractured bones completely. The authors analyzed the bone remodeling after incomplete reduction. These results suggest that the decreased measurements might be caused from the scar contracture with fibrosis. This research is very limited to explain the change while bone remodeling is progressed. Further research should be continued to discover the understanding of the process.
Frontal Hyperostosis in the Patients of Craniosynostosis After Cranial Distraction Osteogenesis
Authors: Kawamoto Koji , Wu Cheng Chun , Imai Keisuke
Published: September 2017

Background:

Conventional fronto-orbital advancement and distraction osteogenesis (DOG) have been used to treat craniosynostosis, both of which are considered effective. During the authors’ practice, a phenomenon of frontal hyperostosis has been observed in the patients of craniosynostosis after DOG, which has yet to be reported in the literature. The purpose of this study is trying to identify the factors related to the phenomenon.

Materials and methods:

From 1997 to 2010, all patients of craniosynostosis undergoing DOG were reviewed. The patient's age at operation, consolidation period, numbers of distractor, distance of distraction, and duration from removal of the distractors to identification of the phenomenon on computed tomography were recorded. The phenomenon was considered positive when the hyperostosis appeared on the frontal bone, where it was neither the osteotomy site nor the previous position of distractor.

Results:

A total of 61 patients were included in this study, including 26 syndromic and 35 nonsyndromic patients. Two syndromic and 6 nonsyndromic patients had the phenomenon. There was no statistical difference between the patients with and without the phenomenon in comparison with the age, number of the distractor, consolidation period, and the distance of distraction.

Conclusion:

Frontal hyperostosis happened in some patients of craniosynostosis after DOG. Although no significant difference was demonstrated, the incidence of hyperostosis was higher in nonsyndromic patients and the patients of hyperostosis had shorter distance of distraction in both syndromic and nonsyndromic groups. Although the definite cause was unknown, we should pay attention to the phenomenon after distraction.
Surgical Success of Tympanoplasty Using Composite Tragal Cartilage in Chronic Otitis Media
Authors: Çiçek Mehmet Melih , Avci Hakan , Şahin Bayram , Acar Şenol , Polat Beldan , Çelik Mehmet , Orhan Kadir Serkan
Published: September 2017

This study aims to investigate the preoperative, postoperative airway hearing threshold levels, and perforation closure rates in patients who underwent primary tragal cartilage tympanoplasty. One hundred seventy-one patients who had chronic otitis media without cholesteatoma underwent primary tragal cartilage tympanoplasty with endaural approach by using underlay technique. Preoperative and postoperative airway hearing threshold levels at 500, 1000, 2000, 4000 Hz frequencies in 8 to 99 months’ follow-up were found and compared with each other. Postoperative perforation closure rates were also investigated. At 500 Hz in 112 patients, at 1000 Hz in 106 patients, at 2000 Hz in 96 patients, and at 4000 Hz in 80 patients, more than 9.5 dB airway hearing gain was determined. The authors found their postoperative perforation closure rate as 84.8%. In conclusion, tragal cartilage tympanoplasty may be chosen as the primary operation technique in primary chronic otitis media patients and by this technique perforation closure rates are also acceptable in addition to satisfactory hearing gain.
Neonatal Mandibular Distraction Without a Consolidation Period: Is It Safe? Is it Effective?
Authors: Biskup Nataliya , Altman Ashley L. , Runyan Christopher M. , Gendron Craig , Babiker Haithem Elhadi , Gordon Christopher B. , Pan Brian S.
Published: September 2017

Purpose:

Consolidation is a standard part of most post-distraction protocols. This study aims to determine whether the deliberate omission of a consolidation period following mandibular distraction (MD) in neonates with Pierre Robin sequence (PRS) affected the airway outcomes and complication rates.

Patients and Methods:

A retrospective chart review of 28 neonates with PRS who underwent MD for severe airway obstruction between 2009 and 2014 was performed. Neonates were split into 2 cohorts: those with a very short or no consolidation (no consolidation group, n = 18) and those with a traditional consolidation period (consolidation group, n = 10).

Results:

Mean consolidation length was 25 days in the conventional consolidation group and 1.5 days in the no consolidation group (P < 0.01). Postoperatively, both groups showed equivalent improvements in their obstructive index as measured by polysomnography. Compared with the patients who underwent convention consolidation, patients in the “no consolidation” group did not require a greater number of repeat distraction, supplemental oxygen, or tracheostomy. Nor was there any significant difference in the number of complications between the 2 groups.

Conclusion:

In neonates with PRS treated with MD for severe airway obstruction, the omission of a consolidation period does not appear to significantly affect the complication rate or resolution of airway obstruction.
Adipose Tissue-Derived Stromal Vascular Fraction Increases Osteogenesis in an Experimental Design Zygomatic Bone Defect Model
Authors: Toplu Gaye , Ozcelik Derya , Serin Merdan , Erdem Havva , Topacoglu Arzu Turkseven
Published: September 2017

Introduction:

Facial bone defects are frequently encountered problems in clinical practice. Bone grafts, flaps, and alloplastic materials are often used in their treatment. This leads to donor site morbidity and prolongation of the operation. The authors have planned this study to examine whether adipose tissue derived stromal vascular fraction (SVF) has an osteogenic effect in the critical sized membranous bone defect of the zygomatic bone.

Materials and Methods:

Twenty male Wistar Albino rats were used. Bilateral zygomatic arches were opened with lateral incisions. A standard 3-mm bone defect was created bilaterally on the zygomatic arches of the rats. In the experiment side, the stem cell-rich SVF that was obtained by applying centrifugal process to the adipose tissue derived from the inguinal fat pad was injected into the site of the right zygomatic arch bone defect. In the control side, left zygomatic arch was left for secondary bone healing without any treatment after a 3-mm critical bone defect was created. In the postoperative 10th (n:5) and 20th weeks (n:13), the healing areas of bone defects were assessed by a 3-dimensional tomography, and then, the rats were sacrificed and bone healing was examined histologically.

Results:

There were no statistically significant differences on the 10th week results. At the 20th week new bone formation amount calculated from the 3-dimensional computed tomography results was significantly higher in the experiment side (P = 0.033). In the histological examination at the 20th week, there was significantly more callus formation in the experiment side (P = 0.0112).

Discussion:

Stem cells can increase the rate of bone healing by differentiating into certain tissues. It is predicted that adipose tissue-derived SVF rich with mesenchymal stem cells can increase bone healing in facial bone defects and this application could replace the use of bone grafts and flaps in clinical practice. As a result, it is concluded that adipose tissue-derived stem cells can potentiate osteogenesis and reduce the possibility of developing necrosis on the bone ends.
Mandibular Osteomyelitis and Cervical Lymphadenitis Due to Mycobacterium abscessus: Surgical Management of a Pediatric Cohort With a Shared Epidemiologic Exposure
Authors: Thompson Peter W. , Williams Joseph K.
Published: September 2017

Background:

Mycobacterium abscessus has been implicated as the cause of various infections in the setting of healthcare-related “outbreaks.” Mandibular osteomyelitis caused by M abscessus is exceedingly rare, with only 1 patient reported in the literature. The authors describe the surgical management of 12 pediatric patients with M abscessus-related mandibular osteomyelitis and cervical lymphadenitis caused by exposure to contaminated water at a regional dental clinic.

Methods:

Following institutional review board approval, new suspected patients were reviewed and followed prospectively. A multidisciplinary team coordinated the surgical approach, antibiotic regimen, and follow-up for each patient.

Results:

Twelve patients (median age 7.5 years) received treatment of M abscessus infection. Eleven had mandibular osteomyelitis and underwent debridement along with extraction of affected teeth. Eight had lymphadenitis and underwent excision of involved nodes. Four patients (in whom surgical debridement was considered inadequate) received antibiotic therapy with a regimen of amikacin, cefoxitin, and azithromycin for 4 months. Nine of 12 patients have been followed for a median of 5 months (range 1–11 months); no patient has evidence of persistent clinical infection. Three of 4 patients treated with amikacin have high-frequency hearing loss.

Conclusions:

The authors describe a pediatric cohort with mandibular osteomyelitis and cervical lymphadenitis due to M abscessus following pulpotomy at a single dental clinic. Diagnosis required a high index of suspicion. Patients in our series had resolution of infection even without antibiotic therapy, suggesting that early complete surgical debridement and removal of affected lymph nodes can be sufficient as a sole treatment modality.
The Morphological Grading and Comparison of Sutural Patency Among Cranial Sutures in Dry Human Skulls
Authors: Cirpan Sibel , Magden Abdurrahman Orhan , Mas Nuket Gocmen , Edizer Mete , Aksu Funda , Yonguc Goksin Nilufer
Published: September 2017

Objective:

To investigate the degree of fusion (patency) among cranial sutures in human dry skulls in the Anatolia.

Methods:

One-hundred fifty-eight human dry skulls that were accepted as adults according to the teeth eruption were macroscopically examined and photographed with Canon 400B (55 mm objective). The grades of fusion of coronal, sagittal, and lambdoid were quantitatively analyzed by using the modified grading scale. According to the extent of patency, the sutures were graded as grade-0 (open), grade-1 (fused but not obliterated), grade-2 (50%< obliterated), grade-3 (50% > obliterated), and grade-4 (100% obliterated). The authors determined and compared the rate for each grade of sutural patency on coronal, sagittal, and lambdoid sutures.

Results:

The cranial sutures of 4 cranii (4/158; 2.53%) had grade-4 fusion, whereas there were no any cranii with sutures of grade-0 fusion. The number of each grade of fusion among cranial sutures of 158 skulls, in descending order, was as follows: 171 (grade-3), 145 (grade-1), 133 (grade-2), and 25 (grade-4). The grade-4 fusion was significantly less observed than the others. The grade-1 and grade-4 fusion of lambdoid sutures were established as the most (66/41.8%) and least (5/3.2%) common fusions among cranial sutures, respectively. The frequencies of each grade of fusion for each cranial suture were determined in a descending order: coronal (grade-3 > 2 > 1 > 4), sagittal (grade-3 > 2 > 1 > 4), and lambdoid sutures (grade-1 > 3 > 2 > 4). The frequency of grade-1 fusion of lambdoid suture (66/41.8%) was significantly different when compared with coronal (39/24.7%) and sagittal sutures (40/25.3%), respectively.

Conclusion:

The grades of fusion (or sutural patency) vary among cranial sutures.
Identification of an Optimal Cut-off for Drain Fluid Amylase on Postoperative Day 1 for Predicting Clinically Relevant Fistula After Distal Pancreatectomy
Authors: Maggino Laura , Malleo Giuseppe , Bassi Claudio , Allegrini Valentina , Beane Joal D. , Beckman Ross M. , Chen Bofeng , Dickson Euan J. , Drebin Jeffrey A. , Ecker Brett L. , Fraker Douglas L. , House Michael G. , Jamieson Nigel B. , Javed Ammar A. , Kowalsky Stacy J. , Lee Major K. , McMillan Matthew T. , Roses Robert E. , Salvia Roberto , Valero Vicente , Velu Lavanniya K. P. , Wolfgang Christopher L. , Zureikat Amer H. , Vollmer Charles M.
Published: September 2017

Objective:

The aim of this study was to investigate the relationship between drain fluid amylase value on the first postoperative day (DFA1) and clinically relevant fistula (CR-POPF) after distal pancreatectomy (DP), and to identify the cut-off of DFA1 that optimizes CR-POPF prediction.

Background:

DFA1 is a well-recognized predictor of CR-POPF after pancreatoduodenectomy, but its role in DP is largely unexplored.

Methods:

DFA1 levels were correlated with CR-POPF in 2 independent multi-institutional sets of DP patients: developmental (n = 338; years 2012 to 2017) and validation cohort (n = 166; years 2006 to 2016). Cut-off choice was based on Youden index calculation, and its ability to predict CR-POPF occurrence was tested in a multivariable regression model adjusted for clinical, demographic, operative, and pathological variables.

Results:

In the developmental set, median DFA1 was 1745 U/L and the CR-POPF rate was 21.9%. DFA1 correlated with CR-POPF with an area under the curve of 0.737 (P < 0.001). A DFA1 of 2000 U/L had the highest Youden index, with 74.3% sensitivity and 62.1% specificity. Patients in the validation cohort displayed different demographic and operative characteristics, lower values of DFA1 (784.5 U/L, P < 0.001), and reduced CR-POPF rate (10.2%, P < 0.001). However, a DFA1 of 2000 U/L had the highest Youden index in this cohort as well, with 64.7% sensitivity and 75.8% specificity. At multivariable analysis, DFA1 ≥2000 U/L was the only factor significantly associated with CR-POPF in both cohorts.

Conclusion:

A DFA1 of 2000 U/L optimizes CR-POPF prediction after DP. These results provide the substrate to define best practices and improve outcomes for patients receiving DP.
A molecular model of the mitochondrial genome segregation machinery inTrypanosoma brucei
Authors: Hoffmann Anneliese , Käser Sandro , Jakob Martin , Amodeo Simona , Peitsch Camille , Týč Jiří , Vaughan Sue , Zuber Benoît , Schneider André , Ochsenreiter Torsten
Published: September 2017

In almost all eukaryotes mitochondria maintain their own genome. Despite the discovery more than 50 years ago still very little is known about how the genome is properly segregated during cell division. The protozoan parasiteTrypanosoma bruceicontains a single mitochondrion with a singular genome the kinetoplast DNA (kDNA). Electron microscopy studies revealed the tripartite attachment complex (TAC) to physically connect the kDNA to the basal body of the flagellum and to ensure proper segregation of the mitochondrial genome via the basal bodies movement, during cell cycle. Using super-resolution microscopy we precisely localize each of the currently known unique TAC components. We demonstrate that the TAC is assembled in a hierarchical order from the base of the flagellum towards the mitochondrial genome and that the assembly is not dependent on the kDNA itself. Based on biochemical analysis the TAC consists of several non-overlapping subcomplexes suggesting an overall size of the TAC exceeding 2.8 mDa. We furthermore demonstrate that the TAC has an impact on mitochondrial organelle positioning however is not required for proper organelle biogenesis or segregation.

Significance Statement

Mitochondrial genome replication and segregation are essential processes in most eukaryotic cells. While replication has been studied in some detail much less is known about the molecular machinery required distribute the replicated genomes. Using super-resolution microscopy in combination with molecular biology and biochemistry we show for the first time in which order the segregation machinery is assembled and that it is assembledde novorather than in a semi conservative fashion in the single celled parasiteTrypanosoma brucei. Furthermore, we demonstrate that the mitochondrial genome itself is not required for assembly to occur. It seems that the physical connection of the mitochondrial genome to cytoskeletal elements is a conserved feature in most eukaryotes, however the molecular components are highly diverse.

Abbreviation

(EZF)

Exclusion zone filaments

(ULF)

Unilateral filament

(TAC)

tripartite attachment complex

(OM)

outer mitochondrial

(IM)

inner mitochondrial

(BSF)

bloodstream form

(PCF)

procyclic form

(kDNA)

kinetoplast DNA

(gRNA)

guide RNA

(SBFSEM)

Serial block face-scanning electron microscopy

(Tet)

tetracyclin

(STED)

Stimulated Emission Depletion
Pharmacodynamic Considerations of Collateral Sensitivity in Design of Antibiotic Treatment Regimen
Authors: Udekwu Klas I. , Weiss Howie
Published: September 2017

Antibiotics have greatly reduced the morbidity and mortality due to infectious diseases. Although antibiotic resistance is not a new problem, its breadth now constitutes a significant threat to human health. One strategy to help combat resistance is to find novel ways to use existing drugs, even those that display high rates of resistance. For the pathogensEscherichia coliandPseudomonas aeruginosa, pairs of antibiotics have been identified for which evolution of resistance to drug A increases sensitivity to drug B and vice versa. These research groups have proposed cycling such pairs to treat infections, similar treatment strategies are being investigated for various cancer forms as well.

While an exciting treatment prospect, no cycling experiments have yet been performed with consideration of pharmacokinetics (PK) and pharmacodynamics (PD). To test the plausibility of this scheme and search for ways to optimize it, we create a mathematical model with explicit PK-PD considerations. We study several possible treatment protocols using pairs of such antibiotics, and investigate the speed of ascent of multiply resistant mutants. Our analyses show that for low concentrations of antibiotics, treatment failure will always occur due to the rapid ascent and fixation of resistant mutants. However, at moderate to high concentrations of some types of bacteriostatic antibiotics with multiday cycling, resistance is prevented from developing and treatment succeeds. This calls for guarded optimism of such treatment protocols whose development can be directed by these types of models.
The whole-genome panorama of cancer drivers
Authors: Sabarinathan Radhakrishnan , Pich Oriol , Martincorena Iñigo , Rubio-Perez Carlota , Juul Malene , Wala Jeremiah , Schumacher Steven , Shapira Ofer , Sidiropoulos Nikos , Waszak Sebastian M. , Tamborero David , Mularoni Loris , Rheinbay Esther , Hornshøj Henrik , Deu-Pons Jordi , Muiños Ferran , Bertl Johanna , Guo Qianyun , Creighton Chad J. , Weischenfeldt Joachim , Korbel Jan O. , Getz Gad , Campbell Peter J. , Pedersen Jakob S. , Beroukhim Rameen , Gonzalez-Perez Abel , López-Bigas Núria ,   on behalf of the PCAWG Drivers and Functional Interpretation Group and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: September 2017

The advance of personalized cancer medicine requires the accurate identification of the mutations driving each patient’s tumor. However, to date, we have only been able to obtain partial insights into the contribution of genomic events to tumor development. Here, we design a comprehensive approach to identify the driver mutations in each patient’s tumor and obtain a whole-genome panorama of driver events across more than 2,500 tumors from 37 types of cancer. This panorama includes coding and non-coding point mutations, copy number alterations and other genomic rearrangements of somatic origin, and potentially predisposing germline variants. We demonstrate that genomic events are at the root of virtually all tumors, with each carrying on average 4.6 driver events. Most individual tumors harbor a unique combination of drivers, and we uncover the most frequent co-occurring driver events. Half of all cancer genes are affected by several types of driver mutations. In summary, the panorama described here provides answers to fundamental questions in cancer genomics and bridges the gap between cancer genomics and personalized cancer medicine.
Forecasting biodiversity in breeding birds using best practices
Authors: Harris David J. , Taylor Shawn D. , White Ethan P
Published: September 2017

Biodiversity forecasts are important for conservation, management, and evaluating how well current models characterize natural systems. While the number of forecasts for biodiversity is increasing, there is little information available on how well these forecasts work. Most biodiversity forecasts are not evaluated to determine how well they predict future diversity, fail to account for uncertainty, and do not use time-series data that captures the actual dynamics being studied. We addressed these limitations by using best practices to explore our ability to forecast the species richness of breeding birds in North America. We used hindcasting to evaluate six different modeling approaches for predicting richness. Hindcasts for each method were evaluated annually for a decade at 1,237 sites distributed throughout the continental United States. All models explained more than 50% of the variance in richness, but none of them consistently outperformed a baseline model that predicted constant richness at each site. The best practices implemented in this study directly influenced the forecasts and evaluations. Stacked species distribution models and “naive” forecasts produced poor estimates of uncertainty and accounting for this resulted in these models dropping in the relative performance compared to other models. Accounting for observer effects improved model performance overall, but also changed the rank ordering of models because it did not improve the accuracy of the “naive” model. Considering the forecast horizon revealed that the prediction accuracy decreased across all models as the time horizon of the forecast increased. To facilitate the rapid improvement of biodiversity forecasts, we emphasize the value of specific best practices in making forecasts and evaluating forecasting methods.
Competing effects of indirect protection and clustering on the power of cluster-randomized controlled vaccine trials
Authors: Hitchings Matt D.T. , Lipsitch Marc , Wang Rui , Bellan Steven E.
Published: September 2017

Power considerations for trials evaluating vaccines against infectious diseases are complicated by indirect protective effects of vaccination. While cluster-randomized trials (cRCTs) are less statistically efficient than individually randomized trials (iRCT), a cRCT’s ability to measure direct and indirect vaccine effects may mitigate the loss of efficiency due to clustering. Within cRCTs, the number and size of clusters affects three determinants of power: the effect size being measured, disease incidence, and intra-cluster correlation. We simulate trials conducted in a collection of small communities to assess how indirect protection and clustering affect the power of cRCTs and iRCTs during an emerging epidemic. Across diverse parameters, we find that within the same trial population, cRCTs are never more powerful than iRCTs, although the difference can be small. We also identify two effects that attenuate the loss of cRCT power traditionally associated with increased cluster size. First, if enrollment of fewer, larger clusters is performed to achieve higher vaccine coverage within vaccinated communities, this increases the effect to be measured and, consequently, power. Second, the greater rate of imported transmission in larger communities may increase the attack rate and similarly mitigate loss of power relative to a trial in many, smaller communities.
High Peak Density Artifacts in Fourier Transform Mass Spectra and their Effects on Data Analysis
Authors: Mitchell Joshua M. , Flight Robert M. , Wang Qing Jun , Kang Woo-Young , Higashi Richard M , Fan Teresa W-M , Lane Andrew N. , Moseley Hunter N.B.
Published: September 2017

Fourier-transform mass spectrometry (FT-MS) allows for the high-throughput and high-resolution detection of thousands of metabolites. Observed spectral features (peaks) that are not isotopologues do not directly correspond to known compounds and cannot be placed into existing metabolic networks. Spectral artifacts account for many of these unidentified peaks, and misassignments made to these artifact peaks can create large interpretative errors. Without accurate identification of artifactual features and correct assignment of real features, discerning their roles within living systems is effectively impossible.

We have observed three types of artifacts unique to FT-MS that often result in regions of abnormally high peak density (HPD), which we collectively refer to as HPD artifacts: i) fuzzy sites representing small regions of m/z space with a ‘fuzzy’ appearance due to the extremely high number of peaks present; ii) ringing due to a very intense peak producing side bands of decreasing intensity that are symmetrically distributed around the main peak; and iii) partial ringing where only a subset of the side bands are observed for an intense peak. Fuzzy sites and partial ringing appear to be novel artifacts previously unreported in the literature and we hypothesize that all three artifact types derive from Fourier transformation-based issues. In some spectra, these artifacts account for roughly a third of the peaks present in the given spectrum. We have developed a set of tools to detect these artifacts and approaches to mitigate their effects on downstream analyses.
Neuronal rhythms orchestrate cell assembles to distinguish perceptual categories
Authors: Goudarzi Morteza Moazami , Cromer Jason , Roy Jefferson , Miller Earl K.
Published: September 2017

Categories are reflected in the spiking activity of neurons. However, how neurons form ensembles for categories is unclear. To address this, we simultaneously recorded spiking and local field potential (LFP) activity in the lateral prefrontal cortex (lPFC) of monkeys performing a delayed match to category task with two independent category sets (Animals: Cats vs Dogs; Cars: Sports Cars vs Sedans). We found stimulus and category information in alpha and beta band oscillations. Different category distinctions engaged different frequencies. There was greater spike field coherence (SFC) in alpha (∼8-14 Hz) for Cats and in beta (∼16-22 Hz) for Dogs. Cars showed similar differences, albeit less pronounced: greater alpha SFC for Sedans and greater beta SFC for Sports Cars. Thus, oscillatory rhythms can help coordinate neurons into different ensembles. Engagement of different frequencies may help differentiate the categories.
Controlling striatal function via anterior frontal cortex stimulation
Authors: Holstein Mieke van , Froböse Monja I. , O’Shea Jacinta , Aarts Esther , Cools Roshan
Published: September 2017

Motivational, cognitive and action goals are processed by distinct, topographically organized, corticostriatal circuits. We aimed to test whether processing in the striatum is und er causal control by cortical regions in the human brain by investigating the effects of offline transcranial magnetic stimulation (TMS) over distinct frontal regions associated with motivational, cognitive and action goal processing. Using a three-session counterbalanced within-subject crossover design, continuous theta burst stimulation was applied over the anterior prefrontal cortex (aPFC), dorsolateral prefrontal cortex, or premotor cortex, immediately after which participants (N=27) performed a paradigm assessing reward anticipation (motivation), task (cognitive) switching, and response (action) switching. Using task-related functional magnetic resonance imaging (fMRI), we assessed the effects of stimulation on processing in distinct regions of the striatum. To account for non-specific effects, each session consisted of a baseline (no-TMS) and a stimulation (post-TMS) fMRI run. Stimulation of the aPFC tended to decrease reward-related processing in the caudate nucleus, while stimulation of the other sites was unsuccessful. A follow-up analysis revealed that aPFC stimulation also decreased processing in the putamen as a function of the interaction between all factors (reward, cognition and action), suggesting stimulation modulated the transfer of motivational information to cortico-striatal circuitry associated with action control.