bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of giant-cell arteritis: from broad spectrum immunosuppressive agents to targeted therapies
Authors: Cid Maria C , Ríos-Garcés Roberto , Terrades-García Nekane , Espígol-Frigolé Georgina
Published: December 2019

For decades, the treatment of GCA has relied on glucocorticoids. Work over the past two decades has supported a modest efficacy of MTX but no clear benefit from anti-TNF-based therapies. More recently, the therapeutic armamentarium for GCA has expanded. The availability of agents targeting specific cytokines, cytokine receptors or signalling pathways, along with a better, although still limited, understanding of the immunopathology of GCA, are opening further therapeutic possibilities. Blocking IL-6 receptor with tocilizumab has been effective in maintaining remission and reducing glucocorticoid exposure and tocilizumab has been approved for the treatment of GCA. However, nearly half of the patients do not benefit from tocilizumab and additional options need to be investigated. This review focuses on standard therapeutic approaches and on targeted therapies that have been or are currently under investigation.
Relapse predictors and serologically unstable condition of IgG4-related disease: a large Chinese cohort
Authors: Liu Yanying , Zeng Qiaozhu , Zhu Lijuan , Gao Jingyuan , Wang Ziqiao , Wang Zhenfan , Yang Fei , Wang Kunkun , Chen Da , Xia Changsheng , Zhang Shanshan , Wang Yi , Shen Danhua , Yu Guangyan , Li Zhan-Guo
Published: December 2019

Objectives

Patients with IgG4-related disease (IgG4-RD) typically respond well to initial glucocorticoid therapy, but always relapse with tapered or maintenance dosage of steroid. We aimed to identify the risk factors for relapse of IgG4-RD and explore the impact of active intervention on the serologically unstable condition.

Methods

We performed a retrospective study of 277 IgG4-RD patients at Peking University People’s Hospital from February 2012 through February 2019. They were all followed for >4 months. The primary outcome was patient relapse. Data on recurrence of IgG4-RD symptoms, laboratory and image findings were recorded, along with information on treatment in the serologically unstable condition.

Results

The cumulative relapse rate was 12.86%, 27.84% and 36.1% at 12, 24 and 36 months, respectively. Younger age at onset, younger age at diagnosis, longer time from diagnosis to treatment and history of allergy were associated with relapse. Identified independent risk factors were longer time from diagnosis to treatment and history of allergy. When serum IgG4 level was 20%, 50% or 100% higher than that of the remission period, similar percentages of patients finally relapsed, regardless of whether they were in the immunosuppression intensified or non-intensified group. Median duration from serum IgG4 level instability to relapse in the intensified and non-intensified group was not statistically different.

Conclusion

The risk factors of relapse were longer time from diagnosis to treatment and history of allergy. Intervention in the serologically unstable condition was not helpful for reducing relapse rate.
Dual orexin receptor antagonists increase sleep and cataplexy in wild type mice
Authors: Mahoney Carrie E , Mochizuki Takatoshi , Scammell Thomas E
Published: December 2019

Orexin receptor antagonists are clinically useful for treating insomnia, but thorough blockade of orexin signaling could cause narcolepsy-like symptoms. Specifically, while sleepiness is a desirable effect, an orexin antagonist could also produce cataplexy, sudden episodes of muscle weakness often triggered by strong, positive emotions. In this study, we examined the effects of dual orexin receptor antagonists (DORAs), lemborexant (E2006) and almorexant, on sleep–wake behavior and cataplexy during the dark period in wild-type (WT) mice and prepro-orexin knockout (OXKO) mice. In WT mice, lemborexant at 10 and 30 mg/kg quickly induced NREM sleep in a dose-dependent fashion. In contrast, lemborexant did not alter sleep–wake behavior in OXKO mice. Under the baseline condition, cataplexy was rare in lemborexant-treated WT mice, but when mice were given chocolate as a rewarding stimulus, lemborexant dose-dependently increased cataplexy. Almorexant produced similar results. Collectively, these results demonstrate that DORAs potently increase NREM and REM sleep in mice via blockade of orexin signaling, and higher doses can cause cataplexy when co-administered with a likely rewarding stimulus.
An Examination of Medical Malpractice Claims Involving Physician Trainees
Authors: Myers Laura C. , Gartland Rajshri M. , Skillings Jillian , Heard Lisa , Bittner Edward A. , Einbinder Jonathan , Metlay Joshua P. , Mort Elizabeth
Published: December 2019

Purpose

To identify patient-, provider-, and claim-related factors of medical malpractice claims in which physician trainees were directly involved in the harm events.

Method

The authors performed a case–control study using medical malpractice claims closed between 2012–2016 and contributed to the Comparative Benchmarking System database by teaching hospitals. Using the service extender flag, they classified claims as cases if physician trainees were directly involved in the harm events. They classified claims as controls if they were from the same facilities, but trainees were not directly involved in the harm events. They performed multivariable regression with predictor variables being patient and provider characteristics. The outcome was physician trainee involvement in harm events.

Results

From the original pool of 30,973 claims, there were 581 cases and 2,610 controls. The majority of cases involved residents (471, 81%). Cases had a statistically significant higher rate of having a trainee named as defendants than controls (184, 32% vs 233, 9%; P < .001). The most common final diagnosis for cases was puncture or laceration during surgery (62, 11%). Inadequate supervision was a contributing factor in 140 (24%) cases overall, with the majority (104, 74%) of these claims being procedure related. Multivariable regression analysis revealed that trainees were most likely to be involved in harm events in specialties such as oral surgery/dentistry and obstetrics–gynecology (OR = 7.99, 95% CI 2.93, 21.83 and OR = 1.85, 95% CI 1.24, 2.66, respectively), when performing procedures (OR = 1.58, 95% CI 1.27, 1.96), or when delivering care in the emergency room (OR = 1.65, 95% CI 1.43, 1.91).

Conclusions

Among claims involving physician trainees, procedures were common and often associated with inadequate supervision. Training directors of surgical specialties can use this information to improve resident supervision policies. The goal is to reduce the likelihood of future harm events.
Comparison of Hip and Knee Arthroplasty Rates of Individuals With and Without Prader-Willi Syndrome
Authors: van Bosse Harold J.P. , Gantz Marie G. , Ong Kevin L. , Cox Jessica B.
Published: December 2019

Background:

Prader-Willi syndrome (PWS) is a complex genetic condition, affecting between 1:10,000 and 1:30,000. The prevalence of hip dysplasia in children with PWS is reportedly between 8% and 30%, but the long-term consequences of residual hip dysplasia remain largely unknown in this population. The purpose of this study was to comparatively estimate the number of total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures performed on adults with and without PWS, using a national hospital discharge database, in an effort to elucidate long-term outcomes and guide clinicians treating orthopaedic concerns in younger individuals with PWS.

Methods:

The National Inpatient Sample of the Healthcare Cost and Utilization Project is the largest all-payer inpatient care database, containing annual data from >7 million hospital stays; sampling weights and stratification variables are provided for producing estimates of >35 million hospitalizations nationwide. THA and TKA procedures were identified, then stratified by whether or not the patient had a diagnosis of PWS. The ages of the 2 groups and sex mix were compared, as was the length of stay for the procedure, and discharge status.

Results:

From 2004 to 2014, 9.4 million patients nationwide, by weighted estimate, underwent THA (3.1 million) or TKA (6.3 million). Sixty-five patients were identified as having the diagnosis of PWS (39 with THA, 26 with TKA); 7 patients per million having hip or knee arthroplasties had PWS. Sixty-eight percent of those with PWS were younger than 50 years, compared with only 7% of those without PWS (P<0.001). The female:male prevalence was 47:53 for patients with PWS and 60:40 for the total group. The mean length of stay was similar, but patients with PWS were more likely to be transferred to another facility after surgery (77% vs. 36%; P=0.008).

Conclusions:

Hip dysplasia prevalence is higher in persons with PWS, but the rate of late treatment with THA is much lower than in the general population. We recommend only active observation for stable and improving hips in young children with PWS, as the consequences of overtreatment can be serious, including further delaying their neuromuscular development, and exposure to possibly unnecessary perioperative risks.

Level of Evidence:

Nation-wide database analysis, Level IV.
Surgical Trends in the Treatment of Supracondylar Humerus Fractures in Early Career Practice: An American Board of Orthopaedic Surgery (ABOS) Part-II Database Study
Authors: Ralles Steven , Murphy Michael , Bednar Michael S. , Fishman Felicity G.
Published: December 2019

Background:

Pediatric supracondylar humerus fractures are the most common elbow injury in children, accounting for 12% to 17% of all childhood fractures. A lack of information exists regarding complication rates on the basis of fellowship status and geography.

Methods:

The American Board of Orthopaedic Surgery (ABOS) Part-II database was used to identify candidates who performed either percutaneous or open treatment of humeral supracondylar or transcondylar fractures between 2002 and 2016 on patients aged 0 to 12 years. Candidates were categorized by fellowship training experience. Information analyzed included fellowship status, surgical procedure, complications, and geographic location of treatment. Data were analyzed utilizing the χ2 and Fischer exact tests and were considered significant if P≤0.05.

Results:

A total of 9169 cases (mean, 5.36+2.27 y; range, 0 to 12) were identified between 2002 and 2016, 8615 of which were treated with closed reduction and percutaneous pinning, whereas 554 were treated with an open procedure. The 5 most common fellowships treating these fractures were listed as pediatrics (4106), sports medicine (1004), none (912), trauma (732), and hand/upper extremity (543). Pediatrics performed the highest number of open reduction and internal fixation (ORIF), however, reported the statistically lowest percentage of ORIF. A statistically significant difference was identified between surgical complication rates and fellowship specialties, with pediatrics having the lowest complication rate (7.0%), followed by no fellowship (8.2%), trauma (9.0%), sports medicine (9.8%), and hand/upper extremity (11.2%) (P<0.001). This significant difference was also present when analyzing closed reduction and percutaneous pinning alone (P=0.002), however, not with the analysis of ORIF.

Conclusions:

Early career pediatric fellowship-trained orthopaedic surgeons are more likely to treat pediatric supracondylar humerus fractures. Overall, although they treat more patients with ORIF than any other group, their percentage treated with ORIF is statistically the lowest. A significant difference in reported complication rates was found to be associated with specific fellowship training, with pediatric fellowship-trained surgeons having the fewest complications and foot/ankle fellowship-trained surgeons associated with the highest rate of reported surgical complications.

Level of Evidence:

Level III—retrospective cohort study.
Near-Infrared–Based Cerebral Oximetry for Prediction of Severe Acute Kidney Injury in Critically Ill Children After Cardiac Surgery
Authors: Flechet Marine , Güiza Fabian , Scharlaeken Isabelle , Vlasselaers Dirk , Desmet Lars , Van den Berghe Greet , Meyfroidt Geert
Published: December 2019

Objectives:

Cerebral oximetry by near-infrared spectroscopy is used frequently in critically ill children but guidelines on its use for decision making in the PICU are lacking. We investigated cerebral near-infrared spectroscopy oximetry in its ability to predict severe acute kidney injury after pediatric cardiac surgery and assessed its additional predictive value to routinely collected data.

Design:

Prospective observational study. The cerebral oximeter was blinded to clinicians.

Setting:

Twelve-bed tertiary PICU, University Hospitals Leuven, Belgium, between October 2012 and November 2015.

Patients:

Critically ill children with congenital heart disease, younger than 12 years old, were monitored with cerebral near-infrared spectroscopy oximetry from PICU admission until they were successfully weaned off mechanical ventilation.

Interventions:

None.

Measurements and Main Results:

The primary outcome was prediction of severe acute kidney injury 6 hours before its occurrence during the first week of intensive care. Near-infrared spectroscopy-derived predictors and routinely collected clinical data were compared and combined to assess added predictive value. Of the 156 children included in the analysis, 55 (35%) developed severe acute kidney injury. The most discriminant near-infrared spectroscopy-derived predictor was near-infrared spectroscopy variability (area under the receiver operating characteristic curve, 0.68; 95% CI, 0.67–0.68), but was outperformed by a clinical model including baseline serum creatinine, cyanotic cardiopathy pre-surgery, blood pressure, and heart frequency (area under the receiver operating characteristic curve, 0.75; 95% CI, 0.75–0.75; p < 0.001). Combining clinical and near-infrared spectroscopy information improved model performance (area under the receiver operating characteristic curve, 0.79; 95% CI, 0.79–0.80; p < 0.001).

Conclusions:

After pediatric cardiac surgery, near-infrared spectroscopy variability combined with clinical information improved discrimination for acute kidney injury. Future studies are required to identify whether supplementary, timely clinical interventions at the bedside, based on near-infrared spectroscopy variability analysis, could improve outcome.
Position Paper on Global Extracorporeal Membrane Oxygenation Education and Educational Agenda for the Future: A Statement From the Extracorporeal Life Support Organization ECMOed Taskforce*
Authors: Zakhary Bishoy , Shekar Kiran , Diaz Rodrigo , Badulak Jenelle , Johnston Lindsay , Roeleveld Peter Paul , Alinier Guillaume , Lai Peter Chi Keung , Ramanathan Kollengode , Moore Elizabeth , Hassan Ibrahim , Agerstrand Cara , Ngai Wallace Chun-wai , Salazar Leonardo , Raman Lakshmi , Bembea Melania M. , Davidson Mark , Gomez-Gutierrez Rene D. , Mateo-Sidrón Jose Alfonso Rubio , Kukutschka Jeannie , Antonini Marta V. , Dickstein Marc L. , Schmidt Matthieu , Abrams Darryl , Ogino Mark T.
Published: December 2019

Objectives:

The purpose of this position paper is two-fold: first, to describe the state of extracorporeal membrane oxygenation education worldwide, noting current limitations and challenges; and second, to put forth an educational agenda regarding opportunities for an international collaborative approach toward standardization.

Design:

Relevant medical literature was reviewed through literature search, and materials from national organizations were accessed through the Internet. Taskforce members generated a consensus statement using an iterative consensus process through teleconferences and electronic communication.

Setting:

In 2018, the Extracorporeal Life Support Organization convened the ECMOed Taskforce at two structured, face-to-face meetings of 40 healthcare practitioners and educators with expertise in caring for the extracorporeal membrane oxygenation patient and in extracorporeal membrane oxygenation education.

Patients:

None.

Interventions:

None.

Measurements and Main Results:

The ECMOed Taskforce identified seven educational domains that would benefit from international collaborative efforts. Of primary importance, the Taskforce outlined actionable items regarding 1) the creation of a standardized extracorporeal membrane oxygenation curriculum; 2) defining criteria for an extracorporeal membrane oxygenation course as a vehicle for delivering the curriculum; 3) outlining a mechanism for evaluating the quality of educational offerings; 4) utilizing validated assessment tools in the development of extracorporeal membrane oxygenation practitioner certification; and 5) promoting high-quality educational research to guide ongoing educational and competency assessment development.

Conclusions:

Significant variability and limitations in global extracorporeal membrane oxygenation education exist. In this position paper, we outline a road map for standardizing international extracorporeal membrane oxygenation education and practitioner certification. Ongoing high-quality educational research is needed to evaluate the impact of these initiatives.
Risk of cancer in individuals with alcohol and drug use disorders: a registry-based study in Reggio Emilia, Italy
Authors: Mancuso Pamela , Djuric Olivera , Collini Giorgia , Serventi Emanuela , Massari Marco , Zerbini Alessandro , Giorgi Rossi Paolo , Vicentini Massimo
Published: December 2019

Aims of this population-based cohort study was to compare the overall and site-specific cancer incidence in individuals with alcohol or drug use disorders with incidence of the general population, and to estimate excess cancer risk in a subgroup of individuals who have hepatitis C virus or HIV infection. The study included 4373 residents of Reggio Emilia province diagnosed with alcohol or drug use disorders during the period from 1 January 1985 to 31 December 2014. All newly diagnosed cancers registered from 1 January 1996 to 31 December 2014 were taken into account to calculate the standardised incidence ratio (SIR) of cancers of any site and of site-specific cancers. SIR of cancer at any site was 1.6 (95% confidence interval [CI] 1.4–1.9). Anogenital cancers were associated with the highest excess risk (SIR=11.9; 95% CI 4.9–28.5), followed by oesophageal (SIR=9.5; 95% CI 3.6–25.3) and cervical cancer (SIR=8.6; 95% CI 2.8–26.7). Excess risk of all cancer sites, except for breast cancer, was observed among individuals with alcohol use disorders and of all cancer sites, except breast and kidney cancers, among individuals with drug use disorders. Among hepatitis C virus-positive individuals, cancer at any site risk was 1.9 (95% CI 1.2–3.1) and among HIV-infected individuals it was 3.3 (95% CI 1.8–5.7). Individuals with alcohol and drug use disorders face a higher risk of various cancers. Effective interventions to prevent or reduce the harm of substance abuse and risky behaviours in this population are warranted.
Age at last birth and risk of developing breast cancer: a meta-analysis
Authors: Wu Yanjun , Wang Mingyue , Sun Wenjun , Li Suyun , Wang Weijing , Zhang Dongfeng
Published: December 2019

Objectives

Results from epidemiologic studies on age at last birth (ALB) and the risk of developing breast cancer were inconsistent. Therefore, we conducted this meta-analysis to evaluate the association between ALB and the risk of developing breast cancer quantitatively.

Methods

Relevant articles published up to May 2019 were identified by searching systematically in PubMed, Web of Science, China National Knowledge Infrastructure, and Wan Fang Med Online. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response relationship was assessed by restricted cubic spline model.

Results

Fourteen studies with 132 133 cases and 1 314 005 participants were eligible for this meta-analysis. The pooled RR (95% CI) of breast cancer for the highest vs. the lowest stratification of ALB was 1.22 (1.04–1.42). In the subgroup analysis, significant positive associations were also found in studies conducted in Europe (RR: 1.21, 95% CI: 1.06–1.38), studies with results adjusted for parity (RR: 1.26, 95% CI: 1.04–1.54), and studies with results adjusted for age at first birth (RR: 1.37, 95% CI: 1.08–1.74). The results of the dose-response analysis indicated that the departure from linearity was NS between ALB and the risk of breast cancer (P
nonlinearity = 0.711), but the linear associations were NS.

Conclusion

This meta-analysis suggested that ALB was positively associated with the risk of breast cancer. The risk of developing breast cancer increased gradually with the ALB for women. Our findings may have implications for family planning.
Effectiveness of vitamin D supplementation on the outcome of pulmonary tuberculosis treatment in adults: a meta-analysis of randomized controlled trials
Authors: Zhang Jing , Chen Chun , Yang Jin
Published: December 2019

Background:

Tuberculosis (TB) is one of the most debilitating diseases worldwide. Current studies have shown that vitamin D plays a significant role in host immune defense againstMycobacterium tuberculosis, but clinical trials reported inconsistent results. Therefore, we systematically reviewed the literature to investigate whether vitamin D supplementation could improve the effect of anti-TB therapy.

Methods:

We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from their inception to February 8th, 2019 for randomized controlled trials on vitamin D supplementation in patients with pulmonary TB receiving anti-TB therapy. The primary outcomes were time to sputum culture and smear conversion and proportion of participants with negative sputum culture. The secondary outcomes were clinical response to treatment and adverse events. A random-effects model was used to pool studies. Data were analyzed using RevMan 5.3 software.

Results:

Five studies with a total of 1126 participants were included in our meta-analysis. Vitamin D supplementation did not shorten the time to sputum culture and smear conversion (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.89–1.23,P = 0.60; HR 1.15, 95% CI 0.93–1.41,P = 0.20, respectively) and did not lead to an increase in the proportion of participants with negative sputum culture (relative risk [RR] 1.04, 95% CI 0.97–1.11,P = 0.32). However, it reduced the time to sputum culture conversion in the sub-group of participants withTaqItt genotype (HR 8.09, 95% CI 1.39–47.09,P = 0.02) and improved the multidrug-resistant (MDR) TB sputum culture conversion rate (RR 2.40, 95% CI 1.11–5.18,P = 0.03). There was no influence on secondary outcomes.

Conclusions:

Vitamin D supplementation had no beneficial effect on anti-TB treatment, but it reduced the time to sputum culture conversion in participants with tt genotype of theTaqIvitamin D receptor gene polymorphism and improved the MDR TB sputum culture conversion rate.
Effects of keto acid supplements on Chinese patients receiving maintenance hemodialysis: a prospective, randomized, controlled, single-center clinical study
Authors: Li Hai-Long , Li Hui , Cao Yi-Fu , Qi Yue , Wang Wei-Qi , Liu Shi-Qin , Yang Chen-Die , Yu Xiao-Yan , Xu Tao , Zhu Yan , Chen Wei , Tao Jian-Ling , Li Xue-Wang
Published: December 2019

Background:

The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear. This study aimed to evaluate the effects of KA supplementation on nutritional status, inflammatory markers, and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patients with MHD without malnutrition.

Methods:

This was a prospective, randomized, controlled, single-center clinical study conducted in 2011 till 2014. Twenty-nine patients with MHD were randomly assigned to a control (n = 14) or a KA (n = 15) group. The control group maintained a dietary protein intake of 0.9 g/kg/day. The KA group received additional KA supplement (0.1 g/kg/day). BIA was used to determine the lean tissue mass, adipose tissue mass, and body cell mass. The patients’ nutritional status, dialysis adequacy, and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test.

Results:

The daily total energy intake for both groups was about 28 kcal/kg/day. After 6 months, the Kt/V (where K is the dialyzer clearance of urea, t is the dialysis time, and V is the volume of the distribution of urea) was 1.33 ± 0.25 in KA group, and 1.34 ± 0.25 in the control group. The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group. In addition, the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group. There were no significant differences between the groups with respect to the anthropometry parameters, dialysis adequacy, serum calcium and phosphorus levels, inflammatory markers, and amino-acid profiles, or in relation to the parameters determined by BIA. Both groups achieved dialysis adequacy and maintained nutritional status during the study.

Conclusions:

In this cohort of Chinese patients with MHD, the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day, maintained well nutritional status during study period. The KA supplement (0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio, nor did it change the patients’ mineral metabolism, inflammatory parameters, or body compositions.
Does An Augmented Reality-based Portable Navigation System Improve the Accuracy of Acetabular Component Orientation During THA? A Randomized Controlled Trial
Authors: Ogawa Hiroyuki , Kurosaka Kenji , Sato Atsuko , Hirasawa Naoyuki , Matsubara Masaaki , Tsukada Sachiyuki
Published: December 2019

Background

We developed an augmented reality (AR)-based portable navigation system in which the surgeon can view the pelvic plane and placement angle of an acetabular cup on the display of a smartphone during THA.

Questions/purposes

(1) Is acetabular component placement more accurate using the AR-based portable navigation system compared with the conventional freehand technique? (2) Is intraoperative measurement of placement angle more accurate when using the AR-based portable navigation system compared with a goniometer?

Methods

Forty-six patients were randomly assigned to undergo acetabular cup placement during THA using the AR-based portable navigation system (AR navigation group) or placement of a mechanical alignment guide (conventional group). All surgeries were performed with the patient in the lateral decubitus position. We compared the absolute value of the difference between the targeted placement angle and postoperative measured placement angle between the groups using two types of imaging (radiography and CT).

Results

In terms of radiographic inclination, the mean differences between the targeted placement angle and postoperative measured angle were smaller in the AR navigation group than in the conventional group for both radiographs and CT images (2.3° ± 1.4° versus 3.9° ± 2.4°, respectively; p = 0.009 and 1.9° ± 1.3° versus 3.4° ± 2.6°, respectively; p = 0.02). There were no differences in radiographic anteversion between the two groups. No complications were associated with the use of the AR-based portable navigation system.

Conclusions

This system yielded no differences in acetabular anteversion accuracy, and no clinically important differences in acetabular inclination. Therefore, at this time we cannot recommend this device as its costs and risks cannot be justified based on the absence of a clinically meaningful difference in cup placement accuracy. Although we detected no complications, this was a small series, and this approach adds both surgical time and pins in the ilium.

Level of Evidence

Level I, therapeutic study.
An overview on transient receptor potential channels superfamily
Authors: Tsagareli Merab G. , Nozadze Ivliane
Published: December 2019

The transient receptor potential (TRP) channel superfamily is comprised of a large group of cation-permeable channels, which display an extraordinary diversity of roles in sensory signaling and are involved in plethora of animal behaviors. These channels are activated through a wide variety of mechanisms and participate in virtually every sensory modality. Modulating TRP channel activity provides an important way to regulate membrane excitability and intracellular calcium levels. This is reflected by the fact that small molecule compounds modulating different TRPs have all entered clinical trials for a variety of diseases. The role of TRPs will be further elucidated in complex diseases of the nervous, intestinal, renal, urogenital, respiratory, and cardiovascular systems in diverse therapeutic areas including pain and itch, headache, pulmonary function, oncology, neurology, visceral organs, and genetic diseases. This review focuses on recent developments in the TRP ion channel-related area and highlights evidence supporting TRP channels as promising targets for new analgesic drugs for therapeutic intervention. This review presents a variety of: (1) phylogeny aspects of TRP channels; (2) some structural and functional characteristics of TRPs; (3) a general view and short characteristics of main seven subfamilies of TRP channels; (4) the evidence for consider TRP channels as therapeutic and analgesic targets; and finally (5) further perspectives of TRP channels research.
Breast and axillary surgery in malignant breast disease: a review focused on literature of 2018 and 2019
Authors: Ditsch Nina , Rubio Isabel T. , Gasparri Maria L. , de Boniface Jana , Kuehn Thorsten
Published: December 2019

Purpose of review

There have been fundamental changes in the surgical approach to breast cancer management over the last decades. The primary objective of achieving locoregional control, however, remains unchanged.

Recent findings

In addition to strategies optimizing systemic treatment and radiotherapy, current discussions focus on improving the surgical approach to breast cancer. Especially in view of the increasingly pivotal role of neoadjuvant chemotherapy NAT/NAC (NACT), gauging the extent of tissue removal in the breast and the width of resection margins in breast-conserving surgery is highly important, as is the extent of axillary surgery. Although sentinel lymph node (SLN)-positive patients always underwent axillary lymph node dissection in the past, this paradigm has been challenged in recent years. Targeted axillary dissection (TAD) has emerged as a new staging option in biopsy-proven node-positive patients who convert to clinical node negativity (cN0) after NACT. TAD combines the removal of the SLN and of the target lymph node marked prior to NACT. The accuracy of axillary staging both before and after NACT plays an important role for prognostication and multidisciplinary treatment plans, while its extent has significant effects on patients’ arm morbidity and quality of life.

The current review focuses on recent evidence regarding surgical management of the breast and axilla in patients with primary breast cancer based on a PubMed and EMBASE literature search for publication years 2018 and 2019.
Prognostic and predictive markers for adjuvant therapy
Authors: Schmidt Marcus
Published: December 2019

Purpose of review

To avoid both overtreatment and undertreatment accurate risk assessment is mandatory. The present review gives an overview of recently published articles covering prognostic and predictive factors for adjuvant therapy in early breast cancer.

Recent findings

Gene expression signatures enhance prognostic accuracy with a high level of evidence. These signatures can be further improved by incorporating traditional pathological factors like tumor size. Newer genomic techniques like next-generation sequencing lead to a deeper understanding of the relationship between somatic mutations and prognosis or prediction of therapeutic efficacy. Furthermore, circulating tumor cells, and circulating cell-free or tumor DNA can lead to a better estimation of the risk of recurrence in early breast cancer. In addition, recent results underscore the prognostic and predictive importance of tumor-infiltrating lymphocytes and subtyping of immune cell infiltrates especially in triple-negative breast cancer.

The current review highlights recent studies improving prognostication and prediction of therapeutic efficacy in early breast cancer. These advances should lead to a better risk stratification and thereby to an improved tailoring of therapies.
Optimizing immunotherapy for gynecologic cancers
Authors: Rubinstein Maria M. , Makker Vicky
Published: December 2019

Purpose of review

This review will provide an update on the most recent clinical developments in immuno-oncology in advanced gynecologic cancers and will also highlight ongoing studies in this field.

Recent findings

Although immune checkpoint blockade (ICB) therapy is rapidly altering the treatment landscape in a myriad of solid tumors, the efficacy of ICB therapy with antibodies directed against CTLA-4, PD-1, and PD-L1 in advanced gynecologic cancers has been limited. The exception has been the PD-1 inhibitor pembrolizumab in microsatellite instability high (MSI-H) or mismatch repair-deficient (dMMR) advanced endometrial cancers, highlighted by the recent conditional approval of pembrolizumab in recurrent/metastatic PD-L1-positive cervical cancers and the accelerated approval of pembrolizumab and lenvatinib in microsatellite stable (MSS) or mismatch repair-proficient (pMMR) advanced endometrial cancer. The discovery of novel, rational ICB combinatorial approaches in advanced gynecologic cancers is highly warranted.

Recent advances in the genomic characterization of gynecologic malignancies have informed clinical trial design. However, improved molecular and immunophenotypic biomarkers to more accurately identify patients who will most benefit from immunotherapeutic approaches are urgently needed. This is especially critical as we attempt to integrate immune-oncology agents, chemotherapy, targeted therapy, and radiation therapy in the management of gynecologic cancers.
Endometrial cancer in the morbidly obese: a review
Authors: Liu Marisa C. , Gardner Austin B. , Wolford Juliet E. , Tewari Krishnansu S.
Published: December 2019

Purpose of review

With a worldwide increase in obesity, there has been an increase in obesity-related diseases. Endometrial cancer is a common cause of cancer for women worldwide. Incidence of endometrial cancer has risen worldwide. Accompanying these patients are risk factors and challenges that may prevent standard of care from being delivered.

Recent findings

The current article describes recent literature describing surgical approaches to the obese patient and special considerations in this population. This article also reviews bariatric surgery and endometrial cancer as well as new updates in radiation, chemotherapy and hormonal therapy research in the obese population.

The current article reviews therapeutics and surgery in the morbidly obese for the treatment of endometrial cancer.
Introducing New Technologies and Techniques into Gynecologic Surgical Practice
Authors: WINKELMAN WILLIAM D. , ROSENBLATT PETER L.
Published: December 2019

The surgery practiced today is not the same as the surgery practiced a generation ago and because of the ever-evolving nature of medicine, ongoing education, and adoption of new technology is vital for all surgeons. New technology has the potential to revolutionize the way we practice medicine; however, it is important to understand the context in which new medical devices arise and to approach new medical devices with a healthy combination of skepticism and optimism. Surgeons should feel comfortable assessing, critiquing, and adopting new technology.
Is there a problem with respect? Risk of neochordal rupture
Authors: Bozso Sabin J. , Shan Shubham D. , Nagendran Jeevan
Published: December 2019

Purpose of review

In this review, we summarize the history of mitral valve repair, discuss the broad principles of neochord preparation and implantation, and highlight comparative outcomes between mitral valve repair strategies while focusing on the risk of neochordal rupture.

Recent findings

There have been several recent studies comparing outcomes been leaflet-resection and nonresection, neochord-based mitral valve repair. Operative mortality was very low regardless of repair strategy; however, the rate of mitral valve reoperation is lower in those that undergo a neochord-based repair with overall lower mean mitral gradients postrepair. The introduction of minimally invasive approaches to mitral valve repair has preferentially favored an increase in neochord-based repair, given the technical simplicity compared with resection-based approaches. In very rare cases, neochord rupture can occur, likely secondary to a combination of chordal calcification and mechanical stress.

The method of performing mitral valve repair with neochord implantation has demonstrated superior durability over leaflet resection approaches with equivalent operative outcomes. Although the risk of neochord rupture exists, it is exceedingly rare, and should not be considered a limitation to a neochord-based mitral valve repair. Recurrent mitral regurgitation secondary to neochord rupture is incredibly rare; however, regular echocardiographic evaluation of these patients appears warranted, especially when follow-up extends over 10 years.
Mantle Cell Lymphoma of Mucosa‐Associated Lymphoid Tissue: A European Mantle Cell Lymphoma Network Study
Authors: Morello Lucia , Rattotti Sara , Giordano Laura , Jerkeman Mats , van Meerten Tom , Krawczyk Katarzyna , Moita Filipa , Marino Dario , Ferrero Simone , Szymczyk Michał , Aurer Igor , El‐Galaly Tarec Christoffer , Di Rocco Alice , Visco Carlo , Carli Giuseppe , Defrancesco Irene , Carlo‐Stella Carmelo , Dreyling Martin , Santoro Armando , Arcaini Luca
Published: December 2019

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Phospho‐Profiling Linking Biology and Clinics in Pediatric Acute Myeloid Leukemia
Authors: Schumich Angela , Prchal‐Murphy Michaela , Maurer‐Granofszky Margarita , Hoelbl‐Kovacic Andrea , Mühlegger Nora , Pötschger Ulrike , Fajmann Sabine , Haas Oskar A. , Nebral Karin , Neuhoff Nils von , Zimmermann Martin , Boztug Heidrun , Rasche Mareike , Dolezal Marlies , Walter Christiane , Reinhardt Dirk , Sexl Veronika , Dworzak Michael N.
Published: December 2019

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Predicting Reduced Tinnitus Burden After Cochlear Implantation in Adults
Authors: Dixon Peter R. , Crowson Matthew , Shipp David , Smilsky Kari , Lin Vincent Y. , Le Trung , Chen Joseph M.
Published: December 2019

Objective:

Explore patient characteristics associated with tinnitus improvement after cochlear implantation.

Study Design:

Retrospective cohort.

Setting:

Tertiary referral.

Patients:

Adults with bilateral severe-to-profound hearing loss and tinnitus.

Interventions:

Unilateral cochlear implantation.

Results:

From 1996 to 2018, 358 patients endorsed pre-implant tinnitus and had ascertainable tinnitus status at 1-year. Clinically significant improvement in Tinnitus Handicap Inventory (THI) (reduction by at least 7-points) was observed in 262 (73.2%) patients, of whom 155 (59.2%) reported complete resolution. Of the 24 characteristics explored, four were identified as independent predictors of improved tinnitus in logistic regression models. In a multivariable model including identified independent predictors, each 10-percentage point increase in baseline hearing in noise test was associated with an 14% reduction in odds of tinnitus resolution or clinically significant improvement (odds ratio [OR] 0.86, 95% confidence limits [CL] 0.77, 0.96) and preoperative use of a hearing aid in the contralateral ear was associated with a 72% reduction (OR 0.28; 95% CL 0.11, 0.73). Each 10-point increase in baseline Hearing Handicap Inventory for Adults (HHI) score was associated with a 28% increase in odds of tinnitus improvement (OR 1.28; 95% CL 1.07, 1.54). Higher baseline burden of tinnitus was associated with higher odds of tinnitus improvement (OR 1.21 per 10-point THI increase, 95% CL 1.04, 1.40).

Conclusions:

Worse residual hearing and higher baseline hearing and tinnitus handicap are associated with higher odds of tinnitus improvement. Expectations of patients seeking reduced tinnitus burden following cochlear implantation should be managed by counselling regarding odds of tinnitus improvement compared to those with similar residual hearing and tinnitus burden.
Systematic Review of Pathogenic GJB2 Variants in the Latino Population
Authors: Bouzaher Malek H. , Worden Cameron P. , Jeyakumar Anita
Published: December 2019

Objectives:

Define the extent to which GJB2-related hearing loss is responsible for non-syndromic hearing loss (NSHL) in the Latino population.

Methods:

Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. PubMed and MEDLINE were accessed from 1966 to 2019 using permutations of the MeSH terms: “Hearing Loss,” “Hearing Impairment,” “Deafness,” “Latin American,” “Latino,” “GJB2,” and “Genetic.” Additionally, countries designated as Latino by the US Office of Management and Bureau were cross-referenced as key terms against the aforementioned search criteria. Exclusion criteria included non-English publications, a non-Latino study population, and literature not investigating GJB2. An allele frequency analysis of pathogenic GJB2 variants in the Latino population was performed and stratified by country of origin and reported ethnicity.

Results:

One hundred twenty two unique studies were identified of which 64 met our inclusion criteria. Forty three studies were included in the GJB2 systematic review. A total of 38 pathogenic GJB2 variants were identified across 20 countries in the Latino population. The prevalence of pathogenic GJB2 variants varied by country; however, were generally uncommon with the exception of c.35delG (p.Gly12Valfs∗) which displayed an allele frequency of 3.1% in the combined Latino population; ranging from 21% in Colombia to 0% in Guatemala.

Conclusion:

Variation in the prevalence of pathogenic GJB2 variants by country likely reflect the heterogeneous nature of ethnic ancestral contributions to the Latino population. Additional research utilizing next generation sequencing might aid in the development of assays for high throughput diagnosis of inherited hearing loss in the multitude of ethnic sub-groups that comprise this and other traditionally marginalized populations.
A Dual-Lumen Percutaneous Cannula for Managing Refractory Right Ventricular Failure
Authors: Badu Bernice , Cain Michael T. , Durham Lucian A. , Joyce Lyle D. , Sundararajan Sakthi , Gaglianello Nunzio , Ishizawar David , Saltzberg Mitchell , Mohammed Asim , Joyce David L.
Published: December 2019

A right ventricular assist device (RVAD) using a dual-lumen percutaneous cannula inserted through the right internal jugular vein (IJV) might improve weaning in patients with refractory right ventricular (RV) failure. However, the reported experience with this cannula is limited. We reviewed the records of all patients receiving RVAD support with this new dual-lumen cannula at our institution between April 2017 and February 2019. We recorded data on weaning, mortality, and device-specific complications. We compared outcomes among three subgroups based on the indications for RVAD support (postcardiotomy, cardiogenic shock, and primary respiratory failure) and against similar results in the literature. Mean (standard deviation [SD]) age of the 40 patients (29 men) was 53 (15.5) years. Indications for implantation were postcardiotomy support in 18 patients, cardiogenic shock in 12, and respiratory failure in 10. In all, 17 (94%) patients in the postcardiotomy group were weaned from RVAD support, five (42%) in the cardiogenic shock group, and seven (70%) in the respiratory failure group, overall higher than those reported in the literature (49% to 59%) for surgically placed RVADs. Whereas published in-hospital mortality rates range from 42% to 50% for surgically placed RVADs and from 41% to 50% for RVADs with percutaneous cannulas implanted through the right IJV, mortality was 11%, 58%, and 40% in our subgroups, respectively. There were no major device-related complications. This percutaneous dual-lumen cannula appears to be safe and effective for managing refractory RV failure, with improved weaning and mortality profile, and with limited device-specific adverse events.
Acute effects of moderate-intensity and high-intensity exercise on hemodynamic and autonomic reactivity to the cold pressor test in young adults with excess body weight
Authors: Meireles Kamila , Peçanha Tiago , Dias André R.L. , Souza Katrice A. , Araújo Jaqueline A. , Silva Juliana S. , Rezende Diego A.N. , Santos Roberto J. , Cambri Lucieli T. , Arsa Gisela
Published: December 2019

Objective:

To investigate the effects of a single session of moderate-intensity and high-intensity interval exercise in cardiovascular reactivity to the cold pressor test in young adults with excess body weight.

Methods:

Twenty-two subjects with excess body weight (23 ± 2 years; 30.0 ± 3.4 kg·m−2) performed three sessions: (1) moderate-intensity exercise (30-minute cycling at 50%–60% of heart rate reserve); (2) high-intensity exercise (four series of 3-minute cycling at 80%–90% of heart rate reserve, interspersed by 2-minute recovery) and (3) control (i.e. 30-minute seated). Before and 30 minutes after the interventions, subjects undertook assessments of SBP/DBP and heart rate in response to the cold pressor test (1-minute rest + 1-minute hand immersed in 4°C water). Reactivity was calculated as the absolute response of SBP, DBP and heart rate to cold pressor test and compared between interventions using a two-way analysis of variance (P < 0.05).

Results:

Neither moderate-intensity exercise or high-intensity interval exercise attenuated SBP/DBP reactivity to cold pressor test compared with control. On the other hand, heart rate reactivity was reduced after moderate-intensity exercise compared with control (1.36 ± 8.35 bpm vs. 5.18 ± 9.45 bpm). Furthermore, moderate-intensity exercise reduced absolute levels of SBP/DBP from pre- to post-intervention.

Conclusion:

A single session of moderate-intensity exercise or high-intensity interval exercise did not reduce the SBP/DBP reactivity to cold pressor test. However, absolute levels of SBP/DBP were lower after moderate-intensity exercise, indicating a hypotensive effect promoted by a single session of moderate-intensity exercise in young adults with excess body weight.
Validation of the Spacelabs 90227 OnTrak device according to the European and British Hypertension Societies as well as the American protocols
Authors: de Greeff Annemarie , Shennan Andrew H.
Published: December 2019

Objective

To assess the static device accuracy of the Spacelabs 90227 OnTrak according to the three most recognized validation protocols, in both adults and children.

Methods

Subjects were recruited and data gathered and analysed according to the European Society of Hypertension (ESH-IP2), the British Hypertension Society (BHS) and the American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Standards Organization (ANSI/AAMI/ISO) protocols.

Results

The device achieved a mean difference ± SD between observers and device for SBP/DBP was 0.9 ± 7/–1.4 ± 6 mmHg (ESH-IP2) and 1.7 ± 8/–1.5/6 mmHg (BHS) Grade A/A. For the ANSI/AAMI/ISO protocol, the average device-observer difference for SBP/DBP was 0.4 ± 7/–1.5 ± 7 mmHg fulfilling the two criteria of the protocol.

Conclusion

The Spacelabs 90227 OnTrak device achieved the criteria of all three recognised validation protocols and can therefore be recommended for clinical use as a static device.