bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Pressure– and Coronary Perfusion Pressure–Targeted Cardiopulmonary Resuscitation Improves 24-Hour Survival From Ventricular Fibrillation Cardiac Arrest
Authors: Naim Maryam Y. , Sutton Robert M. , Friess Stuart H. , Bratinov George , Bhalala Utpal , Kilbaugh Todd J. , Lampe Joshua W. , Nadkarni Vinay M. , Becker Lance B. , Berg Robert A.
Published: July 2016

Objectives:

Treatment algorithms for cardiac arrest are rescuer centric and vary little from patient to patient. The objective of this study was to determine if cardiopulmonary resuscitation–targeted to arterial blood pressure and coronary perfusion pressure rather than optimal guideline care would improve 24-hour survival in a porcine model of ventricular fibrillation cardiac arrest.

Data Sources:

Preclinical animal laboratory using female 3-month-old swine.

Study Selection:

A randomized interventional study.

Data Extraction:

After induction of anesthesia and 7 minutes of untreated ventricular fibrillation, 16 female 3-month-old swine were randomized to 1) blood pressure care: titration of chest compression depth to a systolic blood pressure of 100 mm Hg and vasopressor dosing to maintain coronary perfusion pressure of greater than 20 mm Hg or 2) guideline care: chest compression depth targeted to 51 mm and standard guideline vasopressor dosing. Animals received manual cardiopulmonary resuscitation for 10 minutes before the first defibrillation attempt and standardized postresuscitation care for 24 hours.

Data Synthesis:

Twenty-four–hour survival was more likely with blood pressure care versus guideline care (0/8 vs 5/8; p < 0.03), and all survivors had normal neurologic examinations. Mean coronary perfusion pressure prior to defibrillation was significantly higher with blood pressure care (28 ± 3 vs 10 ± 6 mm Hg; p < 0.01). Chest compression depth was lower with blood pressure care (48 ± 0.4 vs 44 ± 0.5 mm Hg; p < 0.05), and the number of vasopressor doses was higher with blood pressure care (median, 3 [range, 1–7] vs 2 [range, 2–2]; p < 0.01).

Conclusions:

Individualized goal-directed hemodynamic resuscitation targeting systolic blood pressure of 100 mm Hg and coronary perfusion pressure of greater than 20 mm Hg improved 24-hour survival compared with guideline care in this model of ventricular fibrillation cardiac arrest.
Bone Failure in Critical Illness
Authors: Lee Paul , Nair Priya , Eisman John A. , Center Jacqueline R.
Published: July 2016

Objectives:

The origin of systemic inflammatory response syndrome and multiple organ dysfunction syndrome is poorly understood but remains a fundamental concern in the ICU. This paper provides a critical appraisal on whether bone failure may represent an unrecognized component of systemic inflammatory response syndrome/multiple organ dysfunction syndrome.

Data Sources, Data Selection, and Data Extraction:

Search of the PubMed database and manual review of selected articles investigating bone pathophysiology in critical illness.

Data Synthesis:

Bone hyperresorption is highly prevalent among critically ill patients. Bone breakdown releases numerous systemically active cytokines and bone-sequestered toxins, with the capacity to fuel inflammatory hypercytokinaemia and metabolic toxaemia. Anti-resorptive medication inhibits bone break down and preadmission anti-resorptive use is associated with superior survival among critically ill patients.

Conclusions:

We propose that hyperresorptive bone failure is an unrecognised component of systemic inflammatory response syndrome/multiple organ dysfunction syndrome that is causal to critical illness progression. If this hypothesis is valid, bone preservative strategies could reduce the risk of osteoporosis/fractures among ICU survivors, as well as decreasing critical illness mortality.
Acetaminophen-Induced Changes in Systemic Blood Pressure in Critically Ill Patients: Results of a Multicenter Cohort Study
Authors: Cantais Aymeric , Schnell David , Vincent François , Hammouda Zeineb , Perinel Sophie , Balichard Sarah , Abroug Fekri , Zeni Fabrice , Meziani Ferhat , Bornstain Caroline , Darmon Michael
Published: July 2016

Objectives:

We sought to assess the incidence of acetaminophen-induced hypotension. Our secondary objectives were to describe systemic hemodynamic changes and factors associated with this complication.

Design:

Prospective observational study.

Setting:

Three ICUs.

Patients:

Adult patients requiring IV acetaminophen infusion. Arterial pressure was monitored via an arterial catheter for 3 hours. Hypotension was defined as a decrease in the mean arterial pressure of greater than or equal to 15% compared with the baseline.

Results:

Overall, 160 patients were included in this study. Eighty-three patients (51.9%) experienced acetaminophen-induced hypotension according to our definition. In patients with acetaminophen-induced hypotension, the nadir mean arterial pressure was 64 mm Hg (95% CI, 54–74). Hypotension was observed 30 minutes (95% CI, 15–71) after acetaminophen infusion. Changes in mean arterial pressure were closely correlated with decreases in the diastolic arterial pressure (r
2 = 0.92) and to a lesser extent with changes in the pulse pressure (r
2 = 0.18) and heart rate (r
2 = 0.09). Changes in the body temperature were not correlated with changes in mean arterial pressure (r
2 = 0.0002; p = 0.85). None of the patients’ baseline characteristics (shock, use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, lactates, renal replacement therapy, chronic heart disease, and indication for acetaminophen infusion) or clinically relevant characteristics (baseline severity according to Logistic Organ Dysfunction score, need for vasopressors, use of antihypertensive agents, need for mechanical ventilation, or changes in the body temperature) were independently associated with acetaminophen-induced hypotension. Among patients with acetaminophen-induced hypotension, 29 (34.9%) required therapeutic intervention.

Conclusions:

Half of the patients who received IV injections of acetaminophen developed hypotension, and up to one third of the observed episodes necessitated therapeutic intervention. Adequately powered randomized studies are needed to confirm our findings, provide an accurate estimation of the consequences of acetaminophen-induced hypotension, and assess the pathophysiologic mechanisms involved.
Constructing Tumor Vaccines Targeting for Vascular Endothelial Growth Factor (VEGF) by DNA Shuffling
Authors: Bie Nana , Zhao Xiuyun , Li Zhitao , Qi Gaofu
Published: July 2016

Most of tumor antigens are self-proteins with poor antigenicity because of immune tolerance. Here, we describe DNA shuffling for overcoming the tolerance of tumor antigens such as vascular endothelial growth factor (VEGF), a growth factor associated with tumor angiogenesis. VEGF genes from mouse, rat, human, and chicken were randomly assembled to chimeric genes by DNA shuffling for constructing an expression library, then screened by PCR, SDS-PAGE, and immunization. A chimeric protein named as No. 46 was selected from the library with the strongest immunotherapy effects on mouse H22 hepatocellular carcinoma, which could induce long-lasted and high level of antibodies recognizing VEGF in mice. Immunization with this chimeric protein could significantly inhibit tumor angiogenesis, slow down tumor growth, increase the survival rate of tumor-bearing mice, and inhibit the lung metastases of tumor in mouse. Treatment with the anti-VEGF IgG induced by this chimeric protein also significantly inhibited tumor growth and improved the survival rate of tumor-bearing mice, by blocking the tyrosine phosphorylation of ERK1/2 pathway of VEGF-VEGFR interaction. Our study provides an efficient approach to overcome the immune tolerance of self-antigens for developing novel tumor vaccines.
Folliculocentric Lichen Sclerosus et Atrophicus in a 10-Year-Old Girl
Authors: El Habr Constantin , Mannava Kathleen , Koch Sara , Tull Rechelle , Goiburu-Chenu Belen , Strowd Lindsay , Sangueza Omar
Published: July 2016

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory scarring disease with a predilection for the anogenital area; however, 15%–20% of LSA cases are extragenital. The folliculocentric variant is rarely reported and less well understood. The authors report a rare case of extragenital, folliculocentric LSA in a 10-year-old girl. The patient presented to the dermatology clinic for evaluation of an asymptomatic eruption of the arms and legs, with no vaginal or vulvar involvement. Physical examination revealed the presence of numerous 2–4 mm, mostly perifollicular, hypopigmented, slightly atrophic papules and plaques. Many of the lesions had a central keratotic plug. Cutaneous histopathological examination showed features of LSA. Based on clinical and histological findings, folliculocentric extragenital LSA was diagnosed.
An Update on the Level of Evidence for Plastic Surgery Research Published in Plastic and Reconstructive Surgery
Authors: Nguyen Anson , Mahabir Raman C.
Published: July 2016

In 2011, Plastic and Reconstructive Surgery (PRS) implemented a level-of-evidence (LOE) pyramid to bring attention to evidence-based medicine and to promote quality of research. The objective of our study was to examine the current, overall quality of plastic surgery research when compared with that of the previous 30 years. Articles from PRS published in 2013 were culled for information, including LOE based on the assigned score from the LOE pyramid. (Animal, cadaver, and basic science studies; reviews; correspondence; and continuing medical education articles were excluded.) The LOE grades were compared with those from 1983, 1993, and 2003. In 2013, 536 articles were published in PRS; of these, 247 met the inclusion criteria and were included in the analysis. The mean LOE in PRS for 2013 was 3.42. For the year 2003, the mean LOE was 4.16; 1993, 4.25; and 1983, 4.42. Analysis of variance indicated significant improvement in research quality over time (P < 0.001). In 2014, 216 of 489 published articles met the inclusion criteria. The mean LOE of PRS articles in 2014 was 3.33, demonstrating continued higher LOE. There was also a decrease in the percentage of level IV and V studies to 47.2% (from 51.4% in 2013), whereas higher quality level I and II studies had increased to 18.1% (from 17.4%). The quality of plastic surgery research has shown a continued upsurge as evidenced by overall improvement in LOE in published articles over the past 3 decades.
Genetic Causes of Recurrent Pregnancy Loss
Authors: PAGE JESSICA M. , SILVER ROBERT M.
Published: July 2016

Pregnancy loss is one of the most common obstetric complications, affecting over 30% of conceptions. A considerable proportion of losses are due to genetic abnormalities. Indeed, over 50% of early pregnancy losses have been associated with chromosomal abnormalities. Most are due to de novo nondisjunctional events but balanced parental translocations are responsible for a small but important percentage of genetic abnormalities in couples with recurrent pregnancy loss. In the past, assessment of genetic abnormalities was limited to karyotype performed on placental or fetal tissue. However, advances in molecular genetic technology now provide rich genetic information about additional genetic causes of and risk factors for pregnancy loss. In addition, the use of preimplantation genetic testing in couples undergoing in vitro fertilization has the potential to decrease the risk of pregnancy loss from genetic abnormalities. To date, efficacy is uncertain but considerable potential remains. This chapter will review what is known about genetic causes of recurrent pregnancy loss with a focus on novel causes and potential treatments. Remaining knowledge gaps will be highlighted.
Orthopedic Injury in Pregnancy
Authors: GROSS GILAD A. , GEORGE JAMES W.
Published: July 2016

There are many reasons why a woman's pregnancy can put her at risk for orthopedic pain and injury. Given the high percentage of pregnant patients experiencing some degree of musculoskeletal pain, it is surprising that this is not an area of wider study. This chapter takes an evidence based approach to help the reader understand the implications of the numerous anatomic and physiologic changes associated with the gravid state, and how they act to promote both discomfort and injury. One-third of pregnant women in America are obese, further increasing risk. Exercise in most pregnancies is recommended and regarded as safe and thus obstetric care providers need to understand risk, diagnostic techniques and treatments.
First Experience With the ICD 16.5 Mini-Scleral Lens for Optic and Therapeutic Purposes
Authors: Suarez Cyrielle , Madariaga Virginie , Lepage Benoît , Malecaze Marie , Fournié Pierre , Soler Vincent , Galiacy Stéphane , Mély René , Cassagne Myriam , Malecaze François
Published: July 2016

Objectives:

To evaluate the success rate, efficacy, and safety of the ICD 16.5 mini-scleral gas permeable (GP) contact lens.

Methods:

This prospective study included referred consecutive patients with irregular corneas and severe ocular surface disease (OSD) in treatment failure. All patients were fitted with the ICD 16.5 mini-scleral GP lens. Even though we had some limited experience with scleral lenses, it was our first experience with the ICD 16.5 mini-scleral GP lens. Efficacy was assessed by comparing best-corrected visual acuity (BCVA) with the mini-scleral lens to baseline BCVA. A subjective visual functioning questionnaire (comfort score, visual quality score, handling rating, and wearing time) was administered in a face-to-face structured interview.

Results:

Thirty-nine eyes of 23 patients with a mean age of 43±16 years were included. Fitting indications were keratoconus (46%), post-penetrating keratoplasty (21%), other irregular astigmatism (15%), and severe OSD (18%). Twenty-five eyes (64%) were successfully fitted with an 18-month follow-up. The mini-scleral GP lens BCVA was 0.16 logarithm of the minimum angle of resolution (logMAR; 20/25) versus a baseline BCVA of 0.44 logMAR (20/63; P<0.001). Comfort and visual quality scores were 8.5/10 and 7.5/10, respectively. No complications were detected in 96% of the eyes (95% confidence interval, 76.1%–99.4%). One eye experienced corneal graft swelling.

Conclusions:

The present findings suggest that the ICD 16.5 mini-scleral GP lens is an effective and safe alternative for managing challenging corneas in a therapeutic impasse.
Floppy Eyelid Syndrome and Its Determinants in Iranian Adults: A Population-Based Study
Authors: Hashemi Hassan , Rastad Hadith , Emamian Mohammad Hassan , Fotouhi Akbar
Published: July 2016

Objectives:

To estimate the prevalence of floppy eyelid syndrome (FES) and to determine the associated factors in a representative sample of Iranian adult population aged 45 to 69 years.

Methods:

The data were according to the second phase of Shahroud Eye Cohort Study performed in 2014 with 4,737 participants aged 45 to 69 years. Diagnosis of FES was made based on the clinical judgment of the ophthalmologist during ocular examinations. The percentage and confidence intervals (CIs) of the prevalence of FES were reported, and the associated factors were analyzed using simple and multiple logistic regression models.

Results:

In this study, 11.3% of the participants (6.7% of men and 14.6% of women) had FES in at least 1 eye. The prevalence of FES decreased with age. Floppy eyelid syndrome grades 1, 2, and 3 were observed in 72.8%, 21.6%, and 0.6% of the participants, respectively. Although the relationship between age and FES was not significant in men (odds ratio (OR)=0.98, 95% CI: 0.95–1.01), the odds of FES decreased significantly with an increase in age in women (OR=0.94, 95% CI: 0.92–0.96). Body mass index ≥25 (OR=1.65, 95% CI: 1.25–2.18), meibomian gland dysfunction (OR=1.47, 95% CI: 1.18–1.81), and hypertension (OR=1.84, 95% CI: 1.46–2.31) had significant associations with FES.

Conclusion:

The prevalence of FES was 11.3%, and 72.8% of the participants had grade 1 FES. Significant associations were found between FES and other eyelid disorders. Floppy eyelid syndrome was more prevalent in younger women.
Clinical and Microbiological Profile of Bacterial Microbial Keratitis in a Portuguese Tertiary Referral Center—Where Are We in 2015?
Authors: Ferreira Carla Sofia , Figueira Luis , Moreira-Gonçalves Nuno , Moreira Raúl , Torrão Luis , Falcão-Reis Fernando
Published: July 2016

Objectives:

To study the microbial profile, antibiotic susceptibility pattern, risk factors, therapeutic trends, and clinical outcomes for microbial keratitis (MK) in a tertiary health care center.

Methods:

All cases with suspected bacterial keratitis that were followed at consultation from September 2007 to August 2015 were included. Microbial cultures were obtained and patients were managed following an internal protocol.

Results:

Two hundred thirty-five patients were included, with a mean age of 50.01±20.73 years. We obtained a 38.4% culture-positive rate, with higher proportion of gram-positives (70.8%). The commonest agents were Staphylococcus aureus (23.1%), Corynebacterium macginleyi (20.0%), and Pseudomonas aeruginosa (13.8%). Fluoroquinolone susceptibility was 97%, with no trend toward its decrease. A total of 95.7% had local risk factors, being trauma and contact lens wear the most common (28.9% each), with different age and pathogens distributions (P<0.001). Topical fluoroquinolones were first-line treatment in 99%, in association with aminoglycosides in 81.6%. Good initial response was registered in 95.9%, but 4.1% needed to step up treatment to fortified antibiotics, mainly if Pseudomonas (P=0.021). Good outcome was achieved in 81.8%, negatively affected by exposure and herpetic keratitis (P<0.001), central location (P=0.01), presence of Tyndall (P<0.001), corneal edema (P<0.001), and worse initial best-corrected visual acuity (P<0.001), but not Pseudomonas isolate (P=0.724).

Conclusions:

Gram-positives are the most frequent pathogens and shifting trends in the isolate distribution or emergence of resistant strains were not demonstrated. The susceptibility to first-line antibiotic agents remained high. We suggest a more aggressive approach to P. aeruginosa cases or MK presenting with poor outcome variables.
Clinical Outcomes of Ruptured Periorbital and Orbital Dermoid Cysts
Authors: Siah We Fong , Al-Muhaylib Ahmed A. , Rajak Saul , Ziahosseini Kimia , Selva Dinesh , Malhotra Raman , Alsuhaibani Adel H.
Published: July 2016

Purpose:

To evaluate the clinical outcomes of ruptured dermoid cysts.

Methods:

A multicenter, retrospective study of all cases of periorbital and orbital dermoid cysts with histopathological evidence of rupture, including those with clinical rupture, was performed over a 10-year period. Demographics and clinical outcomes of ruptured dermoid cysts were recorded. Persistent inflammation was defined as the presence of edema, erythema, and discomfort for at least 28 days.

Results:

Eighty-six cases of dermoid cysts were identified. Median age was 5.5 (range, 1–63) years. Location of cyst was either periorbital (n = 60, 70%) or orbital (n = 26, 30%). There were 29 cases with clinically apparent rupture: 27 surgically ruptured (93%) and 2 spontaneous rupture (7%). Persistent inflammation was found in 1 spontaneous cyst rupture case (50%) and 1 surgically ruptured cyst (3.7%). Older age (p = 0.01) and bony attachment (p = 0.001) were significant factors for cyst rupture, while there was no influence from cyst location (p = 0.14).

Conclusions:

Persistent inflammation is uncommon after surgical rupture of dermoid cysts, but likely after spontaneous rupture. Older age and bony attachment are risk factors for cyst rupture.
Factors Associated With Emergency Services Use by Patients With Recurrent Myocardial Infarction
Authors: Kirchberger Inge , Amann Ute , Heier Margit , Thilo Christian , Peters Annette , Meisinger Christa
Published: July 2016

Background:

Although emergency medical services (EMS) use is the recommended mode of transport in case of acute coronary symptoms, many people fail to use this service.

Objective:

The objective of this study was to determine factors associated with EMS use in a population-based sample of German patients with recurrent acute myocardial infarction (AMI).

Methods:

The sample consisted of 998 persons with a first and recurrent AMI, recruited from 1985 to 2011. Logistic regression modeling adjusted for sociodemographic, situational, and clinical variables, previous diseases, and presenting AMI symptoms was applied.

Results:

Emergency medical services was used by 48.8% of the patients at first, and 62.6% at recurrent AMI. In first AMI, higher age, history of hyperlipidemia, ST-segment elevation AMI, more than 4 presenting symptoms, symptom onset in daytime, and later year of AMI were significantly related with EMS use. Pain in the upper abdomen and pain between the shoulder blades were significantly less common in EMS users. In recurrent AMI, EMS use at first AMI, presence of any other symptom except chest pain, ST-segment elevation myocardial infarction, and later year of AMI were significantly related with EMS use. Significant predictors of EMS use in recurrent AMI in patients who failed to use EMS at first AMI were unmarried, experience of any symptom except chest symptoms at reinfarction, bundle branch block (first AMI), any in-hospital complication (first AMI), longer duration between first and recurrent AMI, and later year of reinfarction.

Conclusions:

Patients with AMI and their significant others may profit by education about the benefits of EMS use.
Delta Alerts: Changing Outcomes in Geriatric Trauma
Authors: Wiles Lynn L. , Day Mark D. , Harris LeAnna
Published: July 2016

Geriatric trauma patients (GTPs) suffering minor injuries have suboptimal outcomes compared with younger populations. Patients 65 years or older account for 10% of all traumas but 28% of all trauma deaths. This trauma center established a third tier trauma alert specifically targeting GTPs at risk for poor outcomes. A Delta Alert is activated when GTPs suffer injuries that fall outside traditional trauma alert guidelines. Early identification and treatment of injuries and expedited referral to specialty groups have improved our GTPs' outcomes including decreased mortality and length of stay and increased percentage of GTPs who are discharged home.
The thyroid and breast cancer
Authors: Smyth Peter P.A.
Published: July 2016

Purpose of review

The female predominance of diseases of the thyroid and breast makes difficult the separation of an expected association with a causal linkage. This review will examine recent reports on associations between thyroid disease and breast cancer, comparing them with previous studies, with a view to elucidating what pointers are available to suggest either a common pathogenesis or novel thyroid-related therapeutic approach, which might arise from this association.

Recent findings

Reports on thyroid–breast cancer associations are reviewed under the following headings: breast cancer prevalence in different thyroid disorders and their effect on risk and outcome; the possible role of thyroid autoimmunity, thyroid enlargement, effect of radioactive iodine treatment, role of stable iodine, possible joint antigens sodium iodide transporter and thyroid peroxidase and thyroid–breast cancer coincidence.

Current studies on thyroid and breast cancer associations confirm earlier findings of the lack of definitive evidence of a causal relationship. The predominant relationship continues to be hypothyroidism or autoimmune thyroid disease perhaps contributing to increased breast cancer risk or outcomes. However, despite many studies and the findings of meta-analyses, elucidating the mechanisms underlying the association remains elusive. At present, there is little justification for utilizing thyroid insights as a possible therapeutic intervention in breast cancer.
Tumor Necrosis Adds Prognostically Significant Information to Grade in Clear Cell Renal Cell Carcinoma
Authors: Khor Li-Yan , Dhakal Hari P. , Jia Xuefei , Reynolds Jordan P. , McKenney Jesse K. , Rini Brian I. , Magi-Galluzzi Cristina , Przybycin Christopher G.
Published: July 2016

Tumor necrosis has been shown to be an independent predictor of adverse outcome in renal cell carcinoma. A modification of the International Society of Urological Pathology (ISUP) grading system for renal cell carcinomas has recently been proposed, which incorporates the presence of tumor necrosis into grade. The investigators proposing this system found that necrosis added significant prognostic information to ISUP grade. We attempted to describe our experience with the effect of tumor necrosis in relationship to nuclear grade by reviewing the slides from a large consecutive series of localized clear cell renal cell carcinomas from our institution and obtaining long-term clinical follow-up information (overall survival). Of the 842 clear cell renal cell carcinomas reviewed, 265 (31.5%) were ISUP grade 1 or 2, 437 (51.9%) were ISUP grade 3, and 140 (16.6%) were ISUP grade 4. Tumor necrosis was present in 177 (21%) cases. Five hundred and forty-seven (64.9%) cases were stage pT1, 83 (9.9%) were stage pT2, 193 (22.9%) were stage pT3a, and 19 (2.3%) were pT3b or higher. Median follow-up was 73.2 months (range 0.12 to 273.6), and 310 (36.8%) patients died. On univariable analysis, there was no significant difference in outcome for tumors of ISUP grades 1 to 3. After adjustment for age, tumor stage, and tumor size, ISUP grade 4 and necrosis were significant predictors of overall survival on multivariable analysis. When the recently proposed modified grading system incorporating tumor necrosis was applied to our data, there was no significant difference in overall survival between patients with modified grade 1 tumors and those with modified grade 2 tumors (P=0.31); however, there was a statistically significant difference between patients with modified grade 1 or 2 tumors and those with modified grade 3 tumors (P=0.04),and a substantial difference in outcome between those with modified grade 3 and modified grade 4 tumors (P<0.001). When a recursive partitioning approach was applied to our data, patients of a given ISUP grade could be further prognostically separated according to the presence or absence of necrosis and could be divided into 3 statistically significant prognostic groups: (1) non-necrotic ISUP grade 1 to 3 tumors, (2) ISUP grade 1 to 3 tumors with necrosis and ISUP grade 4 tumors with <10% necrosis, and (3) ISUP grade 4 tumors with >10% necrosis. In conclusion, our study shows that tumor necrosis adds additional prognostic information to ISUP grade and that quantification of necrosis can further stratify patients with ISUP grade 4 tumors.
A Clinicopathologic Study of Lennert Lymphoma and Possible Prognostic Factors
Authors: Kurita Daisuke , Miyoshi Hiroaki , Yoshida Noriaki , Sasaki Yuya , Kato Seiichi , Niino Daisuke , Sugita Yasuo , Hatta Yoshihiro , Takei Masami , Makishima Makoto , Ohshima Koichi
Published: July 2016

Lennert lymphoma (LeL) is a variant of peripheral T-cell lymphoma, not otherwise specified. Few clinicopathologic studies have investigated LeL, which is a rare disease. Here, we analyzed the clinicopathologic features of 26 patients with LeL to identify potential prognostic factors. Neoplastic cells positive for CD4, CD8, CD4/CD8, TIA-1, and granzyme B were observed in 21 (80.8%), 4 (15.4%), 1 (3.8%), 4 (15.3%), and 0 (0.0%) patients, respectively. Regarding follicular helper T-cell (TFH) markers, neoplastic cells positive for programmed cell death-1 (PD-1), CXCL13, CD10, and BCL6 were observed in 14 (53.8%), 13 (50.0%), 1 (3.8%), and 0 (0.0%) patients, respectively. Patients with positivity for at least 1 TFH cell marker (PD-1, CXCL13, CD10, and/or BCL6) were defined as being TFH cell marker–positive (n=15) and had a worse prognosis than TFH cell marker–negative patients (n=11) (P=0.011). Clinicopathologic characteristics did not differ significantly between TFH cell marker–positive and marker–negative LeL patients. Moreover, prognosis did not differ significantly between TFH cell marker–positive LeL patients and patients with angioimmunoblastic T-cell lymphoma (AITL) (n=42). Nevertheless, as compared with AITL, TFH cell marker–positive LeL was associated with significantly lower frequencies of B symptoms, skin rash, high-intermediate-risk or high-risk international prognostic index values, expanded follicular dendritic cell meshworks, polymorphic infiltrate, clear cells, and positivity for CD10 and BCL6. Although it may be difficult to definitively distinguish between TFH cell marker–positive LeL and AITL, our results suggest that TFH cell markers are useful for identifying LeL patients who will experience unfavorable outcomes.
BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR Genetic Abnormalities
Authors: Kao Yu-Chien , Sung Yun-Shao , Zhang Lei , Jungbluth Achim A. , Huang Shih-Chiang , Argani Pedram , Agaram Narasimhan P. , Zin Angelica , Alaggio Rita , Antonescu Cristina R.
Published: July 2016

With the advent of next-generation sequencing, an increasing number of novel gene fusions and other abnormalities have emerged recently in the spectrum ofEWSR1-negative small blue round cell tumors (SBRCTs). In this regard, a subset of SBRCTs harboring eitherBCORgene fusions (BCOR-CCNB3,BCOR-MAML3),BCORinternal tandem duplications (ITD), orYWHAE-NUTM2Bshare a transcriptional signature including highBCORmRNA expression, as well as similar histologic features. Furthermore, other tumors such as clear cell sarcoma of kidney (CCSK) and primitive myxoid mesenchymal tumor of infancy also demonstrateBCORITDs and highBCORgene expression. The molecular diagnosis of these variousBCORgenetic alterations requires an elaborate methodology including custom BAC fluorescence in situ hybridization (FISH) probes and reverse transcription polymerase chain reaction assays. As these tumors show high level ofBCORoverexpression regardless of the genetic mechanism involved, either conventional gene fusion or ITD, we sought to investigate the performance of an anti-BCOR monoclonal antibody clone C-10 (sc-514576) as an immunohistochemical marker for sarcomas withBCORgene abnormalities. Thus we assessed the BCOR expression in a pathologically and genetically well-characterized cohort of 25 SBRCTs, spanning variousBCOR-related fusions and ITDs andYWHAE-NUTM2Bfusion. In addition, we included related pathologic entities such as 8 CCSKs and other sarcomas withBCORgene fusions. As a control group we included 20 SBRCTs with various (non-BCOR) genetic abnormalities, 10 fusion-negative SBRCTs, 74 synovial sarcomas, 29 rhabdomyosarcomas, and other sarcoma types. In addition, we evaluated the same study group for SATB2 immunoreactivity, as these tumors also showedSATB2mRNA upregulation. All SBRCTs withBCOR-MAML3andBCOR-CCNB3fusions, as well as most withBCORITD (93%), and all CCSKs showed strong and diffuse nuclear BCOR immunoreactivity. Furthermore, all SBRCTs withYWHAE-NUTM2Balso were positive. SATB2 stain was also positive in tumors withYWHAE-NUTM2B,BCOR-MAML3,BCORITD (75%),BCOR-CCNB3(71%), and a subset of CCSKs (33%). In conclusion, BCOR immunohistochemical stain is a highly sensitive marker for SBRCTs and CCSKs withBCORabnormalities andYWHAE-rearrangements and can be used as a useful diagnostic marker in these various molecular subsets. SATB2 immunoreactivity is also present in the majority of this group of tumors.
Need for Lumbar Puncture in Children Younger Than 12 Months Presenting With Simple Febrile Seizure
Authors: Son Yu Yun , Kim Gun-Ha , Byeon Jung Hye , Eun So-Hee , Eun Baik-Lin
Published: July 2016

Objectives

Recently, conflicting results have been reported regarding the necessity of routine lumbar puncture in children less than 12 months of age with simple febrile seizure. The aims of this study were to evaluate the results of lumbar puncture in children younger than 60 months of age with febrile seizure and to reassess the need for lumbar puncture in children younger than 12 months with simple febrile seizure.

Methods

A retrospective chart review was performed in patients younger than 60 months who presented with febrile seizure and underwent lumbar puncture from January 2005 to January 2015.

Results

A total of 1249 patients presenting with febrile seizure were admitted. Of these, 816 met inclusion criteria for presenting with simple febrile seizure. Lumbar puncture was performed in 75 patients (9.2%; age, mean ± SD, 12.05 ± 9.13 months; male/female, 31/44), who were reviewed. Sixty-six (88.0%) of 75 patients were younger than 12 months. Five patients (6.7%) showed pleocytosis in cerebrospinal fluid, and 4 of them were younger than 1 year of age. Three patients (4.0%) had bacterial meningitis and were 4, 8, and 12 months. Streptococcus pneumoniae (2 patients) and Klebsiella pneumoniae (1 patient) were isolated in cerebrospinal fluid. Nobody had neurologic signs suggesting bacterial meningitis, and all of them completed scheduled immunizations and were up-to-date.

Conclusion

Lumbar puncture should be considered in every child younger than 12 months of age with a simple febrile seizure owing to lack of abnormal neurologic sign even if immunization is up-to-date.
Caretakers' Perspectives on Return Pediatric Emergency Department Visits
Authors: Augustine Erin M. , Kreling Barbara A. , Chamberlain James M.
Published: July 2016

Objectives

Approximately 5% of pediatric patients return to the emergency department (ED) within 72 hours of initial evaluation. The goal of this study was to identify reasons for return visits from the caretaker perspective.

Methods

Two parent focus groups were conducted in November 2012. Parents were excluded from participation if the return visit was unrelated to the initial visit or the child was asked to return (e.g., wound check). The focus groups were audiotaped, transcribed, and analyzed using a thematic content analysis approach.

Results

A total of 13 parents participated. Children were 10 months to 11 years of age (median, 3.1 years). Primary symptoms and diagnoses were related to respiratory (n = 6); gastrointestinal (n = 2); dermatologic (n = 2); musculoskeletal (n = 2); and ear, nose, throat and mouth diseases (n = 1). Return visits occurred 12 to 50 hours (median, 24 hours) after the initial visit. Reasons for return visits were divided into 4 domains: (1) the caretaker's response to the initial visit (e.g., dissatisfaction with medical staff, medical care, or information provided), (2) the child's illness (e.g., continued, worsening, or concerning symptoms), (3) the nature of the ED itself (e.g., subspecialist availability, convenient hours), and (4) follow-up care (e.g., lack of appointments with primary physicians or subspecialists).

Conclusions

Several of the reasons parents identify for return visits are within the locus of control of the ED, and several could be addressed by improving regional health care coordination. Surveys based on these themes will quantitate the reasons for return visits and prioritize future strategies to address the perceived need for return visits.
Behavioral Interventions to Prevent HIV Transmission and Acquisition for Transgender Women: A Critical Review
Authors: Garofalo Robert , Kuhns Lisa M. , Reisner Sari L. , Mimiaga Matthew J.
Published: July 2016

Worldwide, transgender women are at disproportionately higher risk of HIV infection, with the primary mode of infection being condomless anal intercourse. Although very few HIV prevention interventions have been developed and tested specifically for transgender women, growing evidence suggests that behavioral HIV risk reduction interventions for other marginalized groups are efficacious. We outline the current state of knowledge and areas in need of further development in this area.
State of the art of diagnosis of rickettsial diseases: the use of blood specimens for diagnosis of scrub typhus, spotted fever group rickettsiosis, and murine typhus
Authors: Paris Daniel H. , Dumler J. Stephen
Published: July 2016

Purpose of review

With improved malaria control, acute undifferentiated febrile illness studies in tropical regions reveal a startling proportion of rickettsial illnesses, especially scrub typhus, murine typhus, and spotted fever group rickettsioses. Laboratory diagnosis of these infections evolved little over the past 40 years, but combinations of technologies like PCR and loop-mediated isothermal amplification, with refined rapid diagnostic tests and/or ELISA, are promising for guidance for early antirickettsial treatment.

Recent findings

The long-term reliance on serological tests – useful only late in rickettsial infections – has led to underdiagnosis, inappropriate therapies, and undocumented morbidity and mortality. Recent approaches integrate nucleic acid amplification and recombinant protein-based serological tests for diagnosing scrub typhus. Optimized using Bayesian latent class analyses, this strategy increases diagnostic confidence and enables early accurate diagnosis and treatment – a model to follow for lagging progress in murine typhus and spotted fever.

A laboratory diagnostic paradigm shift in rickettsial infections is evolving, with replacement of indirect immunofluorescence assay by the more objective ELISA coupled with nucleic acid amplification assays to expand the diagnostic window toward early infection intervals. This approach supports targeted antirickettsial therapy, reduces morbidity and mortality, and provides a robust evidence base for further development of diagnostics and vaccines.
Vesicosalpingo Fistula: A Case Presentation And Review of The Literature
Authors: Maloney Taylor G. , Kavanagh Alex , Khavari Rose
Published: July 2016

Objectives

To describe a case presentation and perform a review of the literature on vesicosalpingo fistulas.

Methods

An otherwise healthy 32 year-old patient was referred to urology with symptoms of persistent abdominal bloating and urine leakage from the vagina after abdominal conversion of laparoscopic hysterectomy. Two fistula tracts were identified in the bladder during preoperative cystoscopy. The tracts were cannulated with temporary ureteral catheters, and the patient underwent a robotic-assisted laparoscopic repair of a vesicosalpingo and a vesicovaginal fistula.

Results

The patient was discharged on the first postoperative day with an indwelling urinary catheter. A follow-up cystogram performed on the 14th postoperative day demonstrated no evidence of extravasation. There was no evidence of recurrence at a 4-month follow-up visit. This is the first reported robot-assisted laparoscopic repair of a vesicosalpingo fistula and the fifth reported case of a vesicosalpingo fistula in the literature. This is the first reported case of separate vesicosalpingo and vesicovaginal fistulas presenting concurrently in a single patient.

Conclusions

This case presentation with 2 separate fistula tracts emanating from the bladder demonstrates the need to meticulously evaluate each individual fistula tract in order to successfully visualize and address all fistula tracts present in order to mitigate failures and the need for reoperation.
Respiratory failure because of neuromuscular disease
Authors: Howard Robin S.
Published: July 2016

Purpose of review

Understanding the mechanisms and abnormalities of respiratory function in neuromuscular disease is critical to supporting the patient and maintaining ventilation in the face of acute or chronic progressive impairment.

Recent findings

Retrospective clinical studies reviewing the care of patients with Guillain–Barré syndrome and myasthenia have shown a disturbingly high mortality following step-down from intensive care. This implies high dependency and rehabilitation management is failing despite evidence that delayed improvement can occur with long-term care. A variety of mechanisms of phrenic nerve impairment have been recognized with newer investigation techniques, including EMG and ultrasound. Specific treatment for progressive neuromuscular and muscle disease has been increasingly possible particularly for the treatment of myasthenia, metabolic myopathies, and Duchenne muscular dystrophy. For those conditions without specific treatment, it has been increasingly possible to support ventilation in the domiciliary setting with newer techniques of noninvasive ventilation and better airway clearance. There remained several areas of vigorous debates, including the role for tracheostomy care and the place of respiratory muscle training and phrenic nerve/diaphragm pacing.

Recent studies and systematic reviews have defined criteria for anticipating, recognizing, and managing ventilatory failure because of acute neuromuscular disease. The care of patients requiring long-term noninvasive ventilatory support for chronic disorders has also evolved. This has resulted in significantly improved survival for patients requiring domiciliary ventilatory support.
Structural characterization of encapsulated ferritin provides insight into iron storage in bacterial nanocompartments
Authors: He Didi , Hughes Sam , Vanden-Hehir Sally , Georgiev Atanas , Altenbach Kirsten , Tarrant Emma , Mackay C. Logan , Waldron Kevin J. , Clarke David J. , Marles-Wright Jon
Published: July 2016

Ferritins are ubiquitous proteins that oxidise and store iron within a protein shell to protect cells from oxidative damage. We have characterized the structure and function of a new member of the ferritin superfamily that is sequestered within an encapsulin capsid. We show that this encapsulated ferritin (EncFtn) has two main alpha helices, which assemble in a metal dependent manner to form a ferroxidase centre at a dimer interface. EncFtn adopts an open decameric structure that is topologically distinct from other ferritins. While EncFtn acts as a ferroxidase, it cannot mineralize iron. Conversely, the encapsulin shell associates with iron, but is not enzymatically active, and we demonstrate that EncFtn must be housed within the encapsulin for iron storage. This encapsulin nanocompartment is widely distributed in bacteria and archaea and represents a distinct class of iron storage system where the oxidation and mineralization of iron are distributed between two proteins.
Differences in the rare variant spectrum among human populations
Authors: Mathieson Iain , Reich David
Published: July 2016

Mutations occur at vastly different rates across the genome, and populations, leading to differences in the spectrum of segregating polymorphisms. Here, we investigate variation in the rare variant spectrum in a sample of human genomes representing all major world populations. We find at least two distinct signatures of variation. One, consistent with a previously reported signature is characterized by an increased rate of TCC>TTC mutations in people from Western Eurasia and South Asia, likely related to differences in the rate, or efficiency of repair, of damage due to deamination of methylated guanine. We describe the geographic extent of this signature and show that it is detectable in the genomes of ancient, but not archaic humans. The second signature is private to certain Native American populations, and is concentrated at CpG sites. We show that this signature is not driven by differences in the CpG mutation rate, but is a result of the fact that highly mutable CpG sites are more likely to undergo multiple independent mutations across human populations, and the spectrum of such mutations is highly sensitive to recent demography. Both of these effects dramatically affect the spectrum of rare variants across human populations, and should be taken into account when using mutational clocks to make inference about demography.
Changeover from signalling to energy-provisioning lipids during transition from colostrum to mature milk in the giant panda (Ailuropoda melanoleuca)
Authors: Zhang Tong , Watson David G. , Zhang Rong , Hou Rong , Loeffler Kati , Kennedy Malcolm W.
Published: July 2016

Among the large eutherian (placental) mammals, ursids (bears) give birth to the most altricial neonates with the lowest neonatal:maternal body mass ratios. This is particularly exemplified by giant pandas in whom the transition from colostrum to main-phase lactation is unusually prolonged. To examine whether there is compensation for the provision of developmentally important nutrients that other species groups may provide in utero, we examined colostrum and milk lipids from birth until the transition was complete. Lipids known to be developmental signals or their precursors, and those that are fundamental to nervous system construction, such as docosahexaenoic acid (DHA) and phosphatidylserines containing DHA, appear early and then fall dramatically in concentration to a baseline at about 20 days. This also applies to other signalling lipids such as lysophosphatidylserines. The dynamics of lysophosphatidic acid and eicosanoids display a similar pattern, albeit less clearly and with differences between mothers. Triglycerides occur at relatively low levels initially and then increase in concentration with time post-partum until a plateau is reached at about 30 days or later. These patterns indicate an early provision of signalling lipids and their precursors, and lipids crucial to brain, retinal and central nervous system construction, followed by a changeover to lipids for energy metabolism. Thus, in giant pandas, and possibly among ursids in general, lactation is adapted to provisioning a highly altricial neonate to a degree that approximates to an extension of gestation.
Beyond spike-timing-dependent plasticity: a computational study of plasticity gradients across basal dendrites
Authors: Bono Jacopo , Clopath Claudia
Published: July 2016

Synaptic plasticity is thought to be the principal mechanism underlying learning in the brain. Models of plastic networks typically combine point neurons with spike-timing-dependent plasticity (STDP) as the learning rule. However, a point neuron does not capture the complexity of dendrites, which allow non-linear local processing of the synaptic inputs. Furthermore, experimental evidence suggests that STDP is not the only learning rule available to neurons. Implementing biophysically realistic neuron models, we studied how dendrites allow for multiple synaptic plasticity mechanisms to coexist in a single cell. In these models, we compared the conditions for STDP and for the synaptic strengthening by local dendritic spikes. We further explored how the connectivity between two cells is affected by these plasticity rules and the synaptic distributions. Finally, we show how memory retention in associative learning can be prolonged in networks of neurons with dendrites.
Diamond drumhead crystals for X-ray optics applications
Authors: Kolodziej Tomasz , Vodnala Preeti , Terentyev Sergey , Blank Vladimir , Shvyd'ko Yuri
Published: July 2016

Thin (<50 µm) and flawless diamond single crystals are essential for the realization of numerous advanced X-ray optical devices at synchrotron radiation and free-electron laser facilities. The fabrication and handling of such ultra-thin components without introducing crystal damage and strain is a challenge. Drumhead crystals, monolithic crystal structures composed of a thin membrane furnished with a surrounding solid collar, are a solution ensuring mechanically stable strain-free mounting of the membranes with efficient thermal transport. Diamond, being one of the hardest and most chemically inert materials, poses significant difficulties in fabrication. Reported here is the successful manufacture of diamond drumhead crystals in the [100] orientation using picosecond laser milling. Subsequent high-temperature treatment appears to be crucial for the membranes to become defect free and unstrained, as revealed by X-ray topography on examples of drumhead crystals with a 26 µm thick (1 mm in diameter) and a 47 µm thick (1.5 × 2.5 mm) membrane.