bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth hormone regulates the sensitization of developing peripheral nociceptors during cutaneous inflammation
Authors: Liu Xiaohua , Green Kathryn J. , Ford Zachary K. , Queme Luis F. , Lu Peilin , Ross Jessica L. , Lee Frank B. , Shank Aaron T. , Hudgins Renita C. , Jankowski Michael P. 
Published: November 2016

Abstract
Cutaneous inflammation alters the function of primary afferents and gene expression in the affected dorsal root ganglia (DRG). However, specific mechanisms of injury-induced peripheral afferent sensitization and behavioral hypersensitivity during development are not fully understood. Recent studies in children suggest a potential role for growth hormone (GH) in pain modulation. Growth hormone modulates homeostasis and tissue repair after injury, but how GH affects nociception in neonates is not known. To determine whether GH played a role in modulating sensory neuron function and hyperresponsiveness during skin inflammation in young mice, we examined behavioral hypersensitivity and the response properties of cutaneous afferents using an ex vivo hairy skin-saphenous nerve-DRG-spinal cord preparation. Results show that inflammation of the hairy hind paw skin initiated at either postnatal day 7 (P7) or P14 reduced GH levels specifically in the affected skin. Furthermore, pretreatment of inflamed mice with exogenous GH reversed mechanical and thermal hypersensitivity in addition to altering nociceptor function. These effects may be mediated through an upregulation of insulin-like growth factor 1 receptor (IGFr1) as GH modulated the transcriptional output of IGFr1 in DRG neurons in vitro and in vivo. Afferent-selective knockdown of IGFr1 during inflammation also prevented the observed injury-induced alterations in cutaneous afferents and behavioral hypersensitivity similar to that after GH pretreatment. These results suggest that GH can block inflammation-induced nociceptor sensitization during postnatal development leading to reduced pain-like behaviors, possibly by suppressing the upregulation of IGFr1 within DRG.
Diagnosing acute respiratory distress syndrome in resource limited settings: the Kigali modification of the Berlin definition
Authors: Riviello Elisabeth D. , Buregeya Egide , Twagirumugabe Theogene 
Published: November 2016

Purpose of review
The acute respiratory distress syndrome (ARDS) was re-defined by a panel of experts in Berlin in 2012. Although the Berlin criteria improved upon the validity and reliability of the definition, it did not make diagnosis of ARDS in resource limited settings possible. Mechanical ventilation, arterial blood gas measurements, and chest radiographs are not feasible in many regions of the world. In 2014, we proposed and applied the Kigali modification of the Berlin definition in a hospital in Rwanda. This review synthesizes literature from the last 18 months relevant to the Kigali modification.

Recent findings
In the last 18 months, the need for a universally applicable ARDS definition was reinforced by advances in supportive care that can be implemented in resource poor settings. Research demonstrating the variable impact of positive end expiratory pressure on hypoxemia, the validity of using pulse oximetry rather than arterial blood gas to categorize hypoxemia, and the accuracy of lung ultrasound support the use of the Kigali modification of the Berlin definition.

Summary
Studies directly comparing the Berlin definition to the Kigali modification are needed. Ongoing clinical research on ARDS needs to include low-income countries.
Extracorporeal membrane oxygenation: beyond rescue therapy for acute respiratory distress syndrome?
Authors: Combes Alain , Bréchot Nicolas , Luyt Charles-Edouard , Schmidt Matthieu 
Published: November 2016

Purpose of review
This article summarizes the results of past and more recent series on venovenous extracorporeal membrane oxygenation (VV-ECMO) and discusses its potential indications beyond the rescue of patients with lung failure refractory to conventional mechanical ventilation.

Recent findings
Successful VV-ECMO treatment in patients with extremely severe influenza A(H1N1)-associated acute respiratory distress syndrome (ARDS) and positive results of the CESAR trial have led to an exponential use of the technology in recent years. Beyond its currently accepted indication as a salvage therapy in ARDS patients with refractory hypoxemia or unable to tolerate volume-limited strategies, VV-ECMO may improve the outcomes of less severe ARDS patients by facilitating lung-protective ventilation.

Summary
As initiation of VV-ECMO allows significant decrease in tidal volume, plateau and driving pressures, which has been associated with improved survival in ARDS patients, new trials should evaluate the impact of its early initiation in patients with severe but not refractory ARDS.
Should we use driving pressure to set tidal volume?
Authors: Grieco Domenico L. , Chen Lu , Dres Martin , Brochard Laurent 
Published: November 2016

Purpose of review
Ventilator-induced lung injury (VILI) can occur despite use of tidal volume (V

t
) limited to 6 ml/kg of predicted body weight, especially in patients with a smaller aerated compartment (i.e. the baby lung) in which, indeed, tidal ventilation takes place. Because respiratory system static compliance (C
RS) is mostly affected by the volume of the baby lung, the ratio V
T/C
RS (i.e. the driving pressure, ΔP) may potentially help tailoring interventions on V
T setting.

Recent findings
Driving pressure is the ventilatory variable most strongly associated with changes in survival and has been shown to be the key mediator of the effects of mechanical ventilation on outcome in the acute respiratory distress syndrome. Observational data suggest an increased risk of death for patients with ΔP more than 14 cmH2O, but a well tolerated threshold for this parameter has yet to be identified. Prone position along with simple ventilatory adjustments to facilitate CO2 clearance may help reduce ΔP in isocapnic conditions. The safety and feasibility of low-flow extracorporeal CO2 removal in enhancing further reduction in V
T and ΔP are currently being investigated.

Summary
Driving pressure is a bedside available parameter that may help identify patients prone to develop VILI and at increased risk of death. No study had prospectively evaluated whether interventions on ΔP may provide a relevant clinical benefit, but it appears physiologically sound to try titrating V
T to minimize ΔP, especially when it is higher than 14 cmH2O and when it has minimal costs in terms of CO2 clearance.
Topiramate Blood Levels During Polytherapy for Epilepsy in Children
Authors: Toki Taira , Iwasaki Toshiyuki , Ishii Masahiro 
Published: November 2016

Background:
The therapeutic range of topiramate (TPM) blood level is not set because the efficacy and safety are not considered to be related to the level. However, the therapeutic target without side effects is necessary, so the optimal range of TPM blood level was analyzed in this study.

Study Question:
This study was conducted to evaluate the efficacy of TPM over 2 years and the utility of measuring blood levels of TPM during the follow-up of epileptic patients.

Study Design:
Thirty patients (18 males, 12 females; age range, 6 months–15 years) were treated with TPM for epilepsy. The initial dosage of TPM was 1–3 mg·kg−1·d−1. If the effect proved insufficient after 2 weeks, the dosage was increased to 4–9 mg·kg−1·d−1.

Measures and Outcomes:
Blood levels of TPM were measured by liquid chromatography-tandem mass spectrometry at 1, 6, 12, and 24 months after levels reached steady state. The efficacy of TPM was evaluated by the reduction in epileptic seizure rate (RR) at the time of blood sampling. Statistical analysis was performed using the Mann–Whitney U test.

Results:
A positive correlation was seen between blood levels and maintenance dosages, but no correlation was observed between blood levels and RR. Any significant difference was not identified in TPM levels between the effective group (RR ≥50%) and the ineffective group (RR <50%; P = 0.159). In the subgroup of patients who did not use valproic acid, a significant difference in TPM levels was apparent between the effective and ineffective groups (P = 0.029). The optimal range of TPM was advocated 3.5–5.0 μg/mL. The optimal range was set, so that ranges did not overlap between the effective and ineffective groups. No patients experienced any side effects.

Conclusions:
Measuring blood levels of TPM based on the classification of concomitant drugs and adjusting the dosage to reach the optimal range were recommended.
Inter-visit Test-Retest Variability of OCT in Glaucoma
Authors: Pearce John Graham , Maddess Ted 
Published: November 2016

ABSTRACT

Purpose
To determine the inter-visit test-retest variability (TRV) of a spectral domain optical coherence tomograph, the Topcon 3D OCT-2000, in the measurement of optic nerve head topography, peripapillary retinal nerve fiber layer (pRNFL), and macular ganglion cell complex (GCC) parameters in glaucoma patients. We also examine whether TRV with this instrument varies with the extent of glaucomatous damage.

Methods
Twenty-four subjects with varying degrees of glaucoma severity provided 41 eyes with usable results for the study. 3D Disc Retinal Nerve Fiber Layer Analysis and Macula V (GCC) scans were repeated 1 week apart, at the same time of day, to determine the inter-visit TRV. TRV was determined using Bland-Altman limits of agreement (LoA) and the resulting coefficients of repeatability (CR).

Results
The overall horizontal and vertical cup/disc ratio CRs were 0.05 and 0.07, respectively. The GCC CR was 2.9 μm. In contrast, average pRNFL TRV expanded with increasing damage, with the LoA being well fitted by ±(34.67 − 0.294(d)), where d is the pRNFL thickness. A more complex model, with constant LoA of ±5.61 μm at d >82 μm, and linearly expanding TRV below that, achieved marginal significance (P < .06).

Conclusions
The repeatability of GCC measurements with this instrument was excellent. The determination of statistically significant change in average pRNFL should take into account average pRNFL thickness.
Painless Acanthamoeba Keratitis with Normal Vision
Authors: Kwok Pui Wai Rachel , Kam Ka Wai , Jhanji Vishal , Young Alvin L. 
Published: November 2016

ABSTRACT

Purpose
To report an atypical case of contact lens–related Acanthamoeba keratitis.

Case Report
A 15-year-old secondary school female student with a history of soft contact lens wear was referred to our hospital by a private general practitioner for management of right eye redness and discomfort for 2 weeks. Upon examination, the best-corrected visual acuity was 20/20 and 20/16 for her right and left eyes, respectively. There was diffuse radial keratoneuritis noted in the cornea of her right eye without any associated epithelial defect. Corneal scraping was performed to induce epithelial defect over the keratoneuritis area, and it was positive for Acanthamoeba trophozoites. She was treated with amoebicidal therapy consisting of propamidine isethionate 0.1% and polyhexamethylene biguanide 0.02%, for 6 months. The patient did not complain of any ocular pain in the entire course of her disease. She attained a final visual acuity of 20/13 in the affected eye with residual peripheral radial perineuritic scar.

Conclusions
Atypical presentation of Acanthamoeba infection is uncommon. This case should arouse the awareness of an indolent presentation of this potentially sight-threatening disease. Clinicians should have a high level of suspicion in contact lens users who present with corneal abnormalities despite an absence of pain. Microbiological work-up and prompt treatment led to a complete resolution of Acanthamoeba infection in our patient.
Minocycline-Induced Scleral and Dermal Hyperpigmentation
Authors: Haskes Cheryl , Shea Michael , Imondi David 
Published: November 2016

ABSTRACTPurposeTo present a case of minocycline-induced blue scleral pigmentation and discuss the pathophysiology and differential diagnoses. The uses, mechanisms, and other adverse effects of minocycline will also be highlighted.Case ReportAn elderly Caucasian male patient presented for routine ocular examination complaining of blue discoloration to the whites of his eyes. He was found to have bilateral blue scleral pigmentation and blue discoloration to various other dermal areas of his body. The blue pigmentation was also visible in the posterior segment within a scleral crescent around his right optic nerve. This pigmentation was determined to be caused by long-term use of oral minocycline.ConclusionsLong-term minocycline use may induce scleral, dermal, and organ hyperpigmentation, typically blue or black in coloration. The pigmentation may reverse with discontinuation of the medication, but can also be permanent. The exact mechanism of pigment deposition remains uncertain, but several theories have been proposed. While the cosmetic appearance may be dramatic, this side effect is not known to cause any systemic or ocular morbidity.
Intussusception With Cecal Cyst as Lead Point in a Child
Authors: Lai Michelle , Coakley Brian A. , Webber Eric M. , Goldman Ran D. 
Published: November 2016

Abstract
Intussusception is a pediatric abdominal emergency in early childhood involving telescoping of 1 part of the bowel into another part. In most children, the condition is idiopathic with no identifiable lead point. Meckel diverticulum is the most common lead point, followed by polyps and duplication cysts. We describe a case of a boy with intussusception caused by a duplication cyst that was drawn retrograde through the ileocecal valve. The patient presented after a 3-month period of symptomatology and had been considered to have constipation before signs of intestinal obstruction developed. Only mild bowel ischemia was seen during the surgical reduction and resection of the cyst which may suggest an ongoing partial obstruction that eventually became more significant. In children with recurrent abdominal pain, surgeons should consider the possibility of intermittent intussusceptions caused by a duplication cyst.
Abdominal Pain Caused by a Potentially Fatal Attraction
Authors: Mercurio Danielle Claire , Scace Candace , Shah Bhairav , Weiner Evan , Prasad Rajeev 
Published: November 2016

Abstract
Abdominal pain is a challenging presentation in children. Examination findings and etiology vary greatly, spanning a vast spectrum from flatulence to frank peritonitis with septic shock. Here, we discuss a 10-year-old boy with 24 hours of progressively worsening lower abdominal pain, nausea, and subjective fevers. History and physical examination findings were consistent with appendicitis. However, physicians were surprised when the single-view abdominal radiograph showed an unanticipated, somewhat perplexing discovery.
Cohort Study to Assess the Impact of Breast Implants on Breastfeeding
Authors: Filiciani Sandra , Siemienczuk Guillermo F. , Nardín Juan M. , Cappio Bárbara , Albertengo Andrés C. , Nozzi Guillermo , Caggioli Matías 
Published: November 2016

Background:
The objective of this study was to evaluate the impact of breast implant surgery and its approaches on lactation by comparing women with and without breast implants at the time of childbirth.

Methods:
Between April of 2013 and July of 2014, in Rosario (Sanatorio de la Mujer and Centro Quirúrgico Rosario), Argentina, a prospective cohort study of women with and without breast implants was performed. Of a total of 3950 births that occurred during this period, 200 patients with similar anthropometric characteristics (maternal and newborn) were selected. Breastfeeding (exclusive or mixed) was compared with artificial feeding at 24 and 48 hours and 30 days in both groups, and the type of incision was also compared.

Results:
Breastfeeding at 30 days showed a nonsignificant trend favoring the control group (OR, 7.39; 95 percent CI, 0.92 to 339.2). The percentage of women with implants who succeeded in establishing breastfeeding (exclusive or mixed) was very high (93 percent). In the control group, 99 percent of the women were breastfeeding at 30 days. In a comparison of the submammary and areola incision, breastfeeding showed odds ratios of 0.78 (95 percent CI, 0.33 to 1.87) at 24 hours, 1.10 (95 percent CI, 0.48 to 2.56) at 48 hours, and 0.18 (95 percent CI, 0.36 to 1.82) at 30 days.

Conclusions:
This study shows that most patients with breast implants were able to establish breastfeeding. However, there is a higher number of women without implants that established exclusive breastfeeding. No significant difference was found between the different surgical approaches.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
Improving Outcomes in Tendon Repair: A Critical Look at the Evidence for Flexor Tendon Repair and Rehabilitation
Authors: Khor Wee S. , Langer Martin F. , Wong Richard , Zhou Rui , Peck Fiona , Wong Jason K. F. 
Published: November 2016

Learning Objectives:
After reading this article, the participant should be able to: 1. Appreciate the variation and evolution of flexor tendon management 2. Know how to assess the patient who presents with a flexor tendon laceration. 3. Understand the biology of repairing flexor tendon lacerations. 4. Appreciate the technical challenges in flexor tendon repair relating to different zones. 5. Understand the rationale of postoperative hand therapy. 6. Have an overview of the types of secondary tendon surgery.

Background:
Flexor tendon injury constitutes a considerable trauma workload for hand surgeons, and a vast amount of research is dedicated toward improving outcomes in tendon repair. This Continuing Medical Education article aims to provide an up-to-date evidence-based outline of flexor tendon surgery in the hand.

Methods:
The authors reviewed the literature on flexor tendon repairs to include a balanced overview of the experimental and clinical research. For each section, the best levels of evidence were assessed in the context of past research to provide a comprehensive opinion on best management.

Results:
The review highlights current trends in flexor tendon surgery, clinical assessment, anesthetic technique, surgical approach, repair technique, and rehabilitation. Carefully selected illustrations, figures, tables, and video have been used to supplement the findings of the review.

Conclusions:
Early active mobilization remains the only long-term proven strategy to improve outcomes. Incorporating intraoperative mobilization using “wide-awake” surgery could emerge to further improve tendon outcomes. Good surgical approach, meticulous surgery, up-to-date physiotherapy regimens, and patient education remain the cornerstone of obtaining best outcomes.
Molecular Profiling Using Breast Cancer Subtype to Plan for Breast Reconstruction
Authors: Sandberg Lars Johan , Clemens Mark W. , Symmans W. F. , Valero Vicente , Caudle Abigail S. , Smith Benjamin , Kuerer Henry M. , Hsu Limin , Kronowitz Steven J. 
Published: November 2016

Background:
Molecular profiling using breast cancer subtype has an increasing role in the multidisciplinary care of the breast cancer patient. The authors sought to determine the role of breast cancer subtyping in breast reconstruction and specifically whether breast cancer subtyping can determine the need for postmastectomy radiation therapy and predict recurrence-free survival to plan for the timing and technique of breast reconstruction.

Methods:
The authors reviewed prospectively collected data from 1931 reconstructed breasts in breast cancer patients who underwent mastectomy between November of 1999 and December of 2012. Reconstructed breasts were grouped by breast cancer subtype and examined for covariates predictive of recurrence-free survival and need for postmastectomy radiation therapy.

Results:
Of the reconstructed breasts, 753 (39 percent) were luminal A, 538 (27.9 percent) were luminal B, 224 (11.6 percent) were luminal HER2, 143 (7.4 percent) were HER2-enriched, and 267 (13.8 percent) were triple-negative breast cancer. Postmastectomy radiation therapy was delivered in 69 HER2-enriched patients (48.3 percent), 94 luminal HER2 patients (42 percent), 200 luminal B patients (37.2 percent), 99 triple-negative breast cancer patients (37.1 percent), and 222 luminal A patients (29.5 percent) (p < 0.0001). Luminal A cases had better recurrence-free survival than HER2-enriched cases, and triple-negative breast cancer cases had worse recurrence-free survival than HER2-enriched cases. Luminal B and luminal HER2 cases had recurrence-free survival similar to that for HER2-enriched cases. Luminal A subtype was associated with the best recurrence-free survival. Subtyping may have improved the breast surgery planning for 33.1 percent of delayed reconstructions that did not require postmastectomy radiation therapy and 37 percent of immediate reconstructions that did require postmastectomy radiation therapy.

Conclusion:
This study is the first publication in the literature to evaluate breast cancer subtype to stratify risk for decision making in breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Where next with preexposure prophylaxis?
Authors: Nugent Diarmuid , Gilson Richard 
Published: November 2016

Purpose of review
Controlling the HIV epidemic remains a major public health challenge, and there is an urgent need for novel prevention strategies. Preexposure prophylaxis (PrEP) refers to the use of antiretrovirals in HIV-negative people at high risk to prevent infection and has the potential to be an important component in the global effort to end the HIV epidemic by 2030. We review the current evidence for the safety and efficacy of PrEP in its different forms and address emergent issues and concerns regarding its implementation.

Recent findings
Two further randomized control trials report high efficacy of both daily and intermittent PrEP in MSM leading to renewed calls for wider availability of PrEP for this group. Oral tenofovir disoproxil/emtricitabine has been licensed for PrEP in many countries and is well tolerated, safe and effective.

Summary
Oral PrEP is well tolerated and effective in reducing the incidence of HIV infection in individuals at high risk. Implementation in high-income countries is progressing slowly; demonstration projects and trials continue in low and middle-income countries.