bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung-Protective Ventilation Over 6 Years at a Large Academic Medical Center: An Evaluation of Trends, Adherence, and Perceptions of Benefit
Authors: Gao Catherine A. , Howard Frederick M. , Siner Jonathan M. , Candido Thomas D. , Ferrante Lauren E.
Published: February 2021

Objectives:

The main objective of this study was to evaluate trends in set tidal volumes across all adult ICUs at a large academic medical center over 6 years, with a focus on adherence to lung-protective ventilation (≤ 8-cc/kg ideal body weight). A secondary objective was to survey providers on their perceptions of lung-protective ventilation and barriers to its implementation.

Design:

Retrospective observational analysis (primary objective) and cross-sectional survey study (secondary objective), both at a single center.

Participants:

Mechanically ventilated adult patients with a set tidal volume (primary objective) and providers rotating through the Medical and Neurosciences ICUs (secondary objective).

Interventions:

None.

Measurements and Main results:

From 2013 to 2018, the average initial set tidal volume (cc/kg ideal body weight) decreased from 8.99 ± 2.19 to 7.45±1.34 (p < 0.001). The cardiothoracic ICU had the largest change in tidal volume from 11.09 ± 1.96 in 2013 to 7.97 ± 1.03 in 2018 (p < 0.001). Although the majority of tidal volumes across all ICUs were between 6.58 and 8.01 (interquartile range) in 2018, 27% of patients were still being ventilated at volumes greater than 8-cc/kg ideal body weight. Most surveyed respondents felt there was benefit to lung-protective ventilation, though many did not routinely calculate the set tidal volume in cc/kg ideal body weight, and most did not feel it was easily calculable with the current electronic medical record system.

Conclusions:

Despite a trend toward lower tidal volumes over the years, in 2018, over a quarter of mechanically ventilated adult patients were being ventilated with tidal volumes greater than 8 cc/kg. Survey data indicate that despite respondents acknowledging the benefits of lung-protective ventilation, there are barriers to its optimal implementation. Future modifications of the electronic medical record, including a calculator to set tidal volume in cc/kg and the use of default set tidal volumes, may help facilitate the delivery of and adherence to lung-protective ventilation.
Effect of Hospital Linens on Unit-Acquired Pressure Injuries for Adults in Medical ICUs: A Cluster Randomized Controlled Trial
Authors: Montague-McCown Mary , Bena James , Burchill Christian N.
Published: February 2021

Objectives:

Researchers have shown in laboratory studies that different types of fabrics were associated with changes in skin moisture, friction, shear, and temperature that may predispose patients to pressure injury. There was an association between type of fiber used in hospital linens and pressure injury development in previous clinical studies. We examined if bed linens made from a newly developed synthetic fiber fabric affected occurrence rate, time to development, and severity of unit-acquired pressure injury in critically ill adult inpatients.

Design:

Cluster randomized controlled trial.

Setting:

Five adult medical ICUs within one quaternary care center in the Midwest United States.

Patients:

Patients were assigned to a unit based on bed availability. In total, there were 3,332 patients in the study.

INTERVENTIONS:

Participating medical ICUs were randomly assigned to cotton fiber or synthetic fiber linens for the first 6 months of the study period, and assignment reversed after a 14-day washout period for the final 6 months.

Measurements and Main Results:

Unit-acquired pressure injury occurrence rate, time to first unit-acquired pressure injury, and severity were evaluated using generalized mixed effect models with patient as a random effect, and a marginal Cox proportional hazards model with repeated admissions from the same patient accounted for by use of a sandwich estimator of the variance. There were 1,706 patients on cotton fiber linens and 1,626 patients on synthetic fiber linens. Groups were similar on demographics except race and admitting diagnosis groupings. Occurrence rate (p = 0.99), time to development (p = 0.99), and maximum severity of unit-acquired pressure (p = 0.86) were similar between groups before and after controlling for race and admitting diagnosis groupings.

Conclusions:

Linen type did not affect unit-acquired pressure injury occurrence rate, severity, or timing. Standard unit-acquired pressure injury prevention efforts may be more cost-effective than investment in synthetic fiber linens.
Life Support Limitations in Mechanically Ventilated Stroke Patients
Authors: de Montmollin Etienne , Schwebel Carole , Dupuis Claire , Garrouste-Orgeas Maité , da Silva Daniel , Azoulay Elie , Laurent Virginie , Thiéry Guillaume , Grinea Alexandra , Marcotte Guillaume , Oziel Johanna , Gainnier Marc , Siami Shidasp , Reignier Jean , Sztrymf Benjamin , Adrie Christophe , Ruckly Stephane , Sonneville Romain , Timsit Jean-François
Published: February 2021

Objectives:

The determinants of decisions to limit life support (withholding or withdrawal) in ventilated stroke patients have been evaluated mainly for patients with intracranial hemorrhages. We aimed to evaluate the frequency of life support limitations in ventilated ischemic and hemorrhagic stroke patients compared with a nonbrain-injured population and to determine factors associated with such decisions.

Design:

Multicenter prospective French observational study.

Setting:

Fourteen ICUs of the French OutcomeRea network.

PATIENTS:

From 2005 to 2016, we included stroke patients and nonbrain-injured patients requiring invasive ventilation within 24 hours of ICU admission.

INTERVENTION:

None.

MEASUREMENTS AND MAIN RESULTS:

We identified 373 stroke patients (ischemic, n = 167 [45%]; hemorrhagic, n = 206 [55%]) and 5,683 nonbrain-injured patients. Decisions to limit life support were taken in 41% of ischemic stroke cases (vs nonbrain-injured patients, subdistribution hazard ratio, 3.59 [95% CI, 2.78–4.65]) and in 33% of hemorrhagic stroke cases (vs nonbrain-injured patients, subdistribution hazard ratio, 3.9 [95% CI, 2.97–5.11]). Time from ICU admission to the first limitation was longer in ischemic than in hemorrhagic stroke (5 [3–9] vs 2 d [1–6] d; p < 0.01). Limitation of life support preceded ICU death in 70% of ischemic strokes and 45% of hemorrhagic strokes (p < 0.01). Life support limitations in ischemic stroke were increased by a vertebrobasilar location (vs anterior circulation, subdistribution hazard ratio, 1.61 [95% CI, 1.01–2.59]) and a prestroke modified Rankin score greater than 2 (2.38 [1.27–4.55]). In hemorrhagic stroke, an age greater than 70 years (2.29 [1.43–3.69]) and a Glasgow Coma Scale score less than 8 (2.15 [1.08–4.3]) were associated with an increased risk of limitation, whereas a higher nonneurologic admission Sequential Organ Failure Assessment score was associated with a reduced risk (per point, 0.89 [0.82–0.97]).

Conclusions:

In ventilated stroke patients, decisions to limit life support are more than three times more frequent than in nonbrain-injured patients, with different timing and associated risk factors between ischemic and hemorrhagic strokes.
Intranasal Orexin After Cardiac Arrest Leads to Increased Electroencephalographic Gamma Activity and Enhanced Neurologic Recovery in Rats
Authors: Sherman David L. , Williams Autumn , GD Sahithi , Modi Hiren R. , Wang Qihong , Thakor Nitish V. , Geocadin Romergryko G.
Published: February 2021

Objectives:

Prolonged cardiac arrest is known to cause global ischemic brain injury and functional impairment. Upon resuscitation, electroencephalographic recordings of brain activity begin to resume and can potentially be used to monitor neurologic recovery. We have previously shown that intrathecal orexin shows promise as a restorative drug and arousal agent in rodents. Our goal is to determine the electrophysiology effects of orexin in a rodent model of asphyxial cardiac arrest, focusing on the electroencephalographic activity in the gamma and super-gamma bands (indicative of return of higher brain function).

Design:

Experimental animal study.

Setting:

University-based animal research laboratory.

Subjects:

Adult male Wistar rats.

Interventions:

In an established model of asphyxial cardiac arrest (n = 24), we treated half of Wistar rats with orexin administered intranasally by atomizer 30 minutes post return of spontaneous circulation in one of two dose levels (10 and 50 µM); the rest were treated with saline as control. Continuous electroencephalographic recording was obtained and quantitatively analyzed for the gamma fraction. Gamma and high-frequency super-gamma band measures were compared against clinical recovery according to Neuro-Deficit Score.

Measurements and Main Results:

Compared with the control cohort, the high-dose orexin cohort showed significantly better Neuro-Deficit Score 4 hours after return of spontaneous circulation (55.17 vs 47.58; p < 0.02) and significantly higher mean gamma fraction (0.251 vs 0.177; p < 0.02) in cerebral regions surveyed by rostral electrodes for the first 170 minutes after administration of orexin.

Conclusions:

Our findings support early and continuous monitoring of electroencephalography-based gamma activity as a marker of better functional recovery after intranasal administration of orexin as measured by Neuro-Deficit Score in an established animal model of asphyxial cardiac arrest.
Early Impella Support in Postcardiac Arrest Cardiogenic Shock Complicating Acute Myocardial Infarction Improves Short- and Long-Term Survival*
Authors: Chatzis Georgios , Markus Birgit , Luesebrink Ulrich , Ahrens Holger , Divchev Dimitar , Syntila Styliani , Scheele Nora , Al Eryani Hanna , Tousoulis Dimitris , Schieffer Bernhard , Karatolios Konstantinos
Published: February 2021

OBJECTIVES:

Early mechanical circulatory support with Impella may improve survival outcomes in the setting of postcardiac arrest cardiogenic shock after out-of-hospital cardiac arrest complicating acute myocardial infarction. However, the optimal timing to initiate mechanical circulatory support in this particular setting remains unclear. Therefore, we aimed to compare survival outcomes of patients supported with Impella 2.5 before percutaneous coronary intervention (pre-PCI) with those supported after percutaneous coronary intervention (post-PCI).

DESIGN:

Retrospective single-center study between September 2014 and December 2019 admitted to the Cardiac Arrest Center in Marburg, Germany.

PATIENTS:

Out of 2,105 patients resuscitated from out-of-hospital cardiac arrest due to acute myocardial infarction with postcardiac arrest cardiogenic shock between September 2014 and December 2019 and admitted to our regional cardiac arrest center, 81 consecutive patients receiving Impella 2.5 during admission coronary angiogram were identified.

OUTCOMES/MEASUREMENTS:

Survival outcomes were compared between those with Impella support pre-PCI to those with support post-PCI.

MAIN RESULTS:

A total of 81 consecutive patients with infarct-related postcardiac arrest shock supported with Impella 2.5 during admission coronary angiogram were included. All patients were in profound cardiogenic shock requiring catecholamines at admission. Overall survival to discharge and at 6 months was 40.7% and 38.3%, respectively. Patients in the pre-PCI group had a higher survival to discharge and at 6 months as compared to patients of the post-PCI group (54.3% vs 30.4%; p = 0.04 and 51.4% vs 28.2%; p = 0.04, respectively). Furthermore, the patients in the early support group demonstrated a greater functional recovery of the left ventricle and a better restoration of the end-organ function when Impella support was initiated prior to percutaneous coronary intervention.

CONCLUSIONS:

Our results suggest that the early initiation of mechanical circulatory support with Impella 2.5 prior to percutaneous coronary intervention is associated with improved hospital and 6-month survival in patients with postcardiac arrest cardiogenic shock complicating acute myocardial infarction.
Sharing ICU Patient Data Responsibly Under the Society of Critical Care Medicine/European Society of Intensive Care Medicine Joint Data Science Collaboration: The Amsterdam University Medical Centers Database (AmsterdamUMCdb) Example*
Authors: Thoral Patrick J. , Peppink Jan M. , Driessen Ronald H. , Sijbrands Eric J. G. , Kompanje Erwin J. O. , Kaplan Lewis , Bailey Heatherlee , Kesecioglu Jozef , Cecconi Maurizio , Churpek Matthew , Clermont Gilles , van der Schaar Mihaela , Ercole Ari , Girbes Armand R. J. , Elbers Paul W. G.
Published: February 2021

OBJECTIVES:

Critical care medicine is a natural environment for machine learning approaches to improve outcomes for critically ill patients as admissions to ICUs generate vast amounts of data. However, technical, legal, ethical, and privacy concerns have so far limited the critical care medicine community from making these data readily available. The Society of Critical Care Medicine and the European Society of Intensive Care Medicine have identified ICU patient data sharing as one of the priorities under their Joint Data Science Collaboration. To encourage ICUs worldwide to share their patient data responsibly, we now describe the development and release of Amsterdam University Medical Centers Database (AmsterdamUMCdb), the first freely available critical care database in full compliance with privacy laws from both the United States and Europe, as an example of the feasibility of sharing complex critical care data.

SETTING:

University hospital ICU.

SUBJECTS:

Data from ICU patients admitted between 2003 and 2016.

INTERVENTIONS:

We used a risk-based deidentification strategy to maintain data utility while preserving privacy. In addition, we implemented contractual and governance processes, and a communication strategy. Patient organizations, supporting hospitals, and experts on ethics and privacy audited these processes and the database.

MEASUREMENTS AND MAIN RESULTS:

AmsterdamUMCdb contains approximately 1 billion clinical data points from 23,106 admissions of 20,109 patients. The privacy audit concluded that reidentification is not reasonably likely, and AmsterdamUMCdb can therefore be considered as anonymous information, both in the context of the U.S. Health Insurance Portability and Accountability Act and the European General Data Protection Regulation. The ethics audit concluded that responsible data sharing imposes minimal burden, whereas the potential benefit is tremendous.

CONCLUSIONS:

Technical, legal, ethical, and privacy challenges related to responsible data sharing can be addressed using a multidisciplinary approach. A risk-based deidentification strategy, that complies with both U.S. and European privacy regulations, should be the preferred approach to releasing ICU patient data. This supports the shared Society of Critical Care Medicine and European Society of Intensive Care Medicine vision to improve critical care outcomes through scientific inquiry of vast and combined ICU datasets.
Efficacy of Serum Angiotensin II Levels in Prognosis of Patients With Coronavirus Disease 2019
Authors: Ozkan Seda , Cakmak Fatih , Konukoglu Dildar , Biberoglu Serap , Ipekci Afsin , Akdeniz Yonca Senem , Bolayirli Ibrahim Murat , Balkan Ilker Inanc , Dumanli Guleren Yartas , Ikizceli Ibrahim
Published: February 2021

OBJECTIVES:

We aimed to determine serum angiotensin II levels in patients with coronavirus disease 2019 infection and to investigate the effect of these levels on the prognosis of the disease.

DESIGN:

The study was planned prospectively and observationally.

SETTING:

The study was conducted in a tertiary university hospital.

PATIENTS:

Coronavirus disease 2019 patients older than 18 years old, polymerase chain reaction test positive, with signs of pneumonia on tomography, and hospitalized were included in the study. ICU need, development of acute respiratory distress syndrome, and in-hospital mortality were considered as primary endpoints.

INTERVENTIONS:

Blood samples were taken from patients three times for angiotensin II levels.

MEASUREMENTS AND MAIN RESULTS:

Angiotensin II levels were studied by enzyme-linked immunosorbent assay method. The SPSS 24.0 program (Statistics Program for Social Scientists, SPSS, Chicago, IL) was used to analyze the data. A total of 112 patients were included in the study, of which 63.4% of the patients were men. The serum angiotensin II levels were statistically significantly lower in the patients with coronavirus disease 2019 compared with the healthy control group (p < 0.001). There was no statistical significance between the serum angiotensin II levels measured at three different times (p > 0.05). The serum angiotensin II levels of the patients with acute respiratory distress syndrome were found to be statistically significantly lower than those without acute respiratory distress syndrome in three samples collected at different clinical periods (p < 0.05). The angiotensin II levels of the patients who required admission to the ICU at all three times of blood sample collection were found to be statistically significantly lower than those who did not (p < 0.05). Although the serum angiotensin II levels of the patients who died were low, there was no statistically significant difference in mortality at all three times (p > 0.05).

CONCLUSIONS:

The serum angiotensin II levels decrease significantly in patients with coronavirus disease 2019, and this decrease is correlated with lung damage.
A challenging frontier – the genomics and therapeutics of nonclear cell renal cell carcinoma
Authors: Patel Hiren V. , Srivastava Arnav , Srinivasan Ramaprasad , Singer Eric A.
Published: February 2021

Purpose of review

As molecular profiling of renal cell carcinoma (RCC) continues to elucidate novel targets for nonclear cell histologies, understanding the landscape of these targets is of utmost importance. In this review, we highlight the genomic landscape of nonclear cell RCC and its implications for current and future systemic therapies.

Recent findings

Several genomic studies have described the mutational burden among nonclear cell histologies. These studies have highlighted the importance of MET in papillary RCC and led to several clinical trials evaluating the efficacy of MET inhibitors for papillary RCC. The success of immune checkpoint inhibitors, such as ipilimumab and nivolumab, in clear cell RCC has led to ongoing trials evaluating these novel therapeutics in nonclear cell RCC.

Genomic profiling has allowed for the evaluation of novel targets for nonclear cell RCC. This evolving therapeutic landscape is being explored in promising, ongoing trials that have the potential for changing how nonclear cell RCC is managed.
The association between dietary vitamin B12 and lung cancer risk: findings from a prospective cohort study
Authors: Luu Hung N. , Wang Renwei , Jin Aizhen , Koh Woon-Puay , Yuan Jian-Min
Published: February 2021

Background

Since previous epidemiological studies reported inconsistent associations between dietary vitamin B12 intake and lung cancer risk, more studies are warranted to clarify this association in different populations.

Methods

The association between dietary B12 intake and lung cancer risk was examined in the Singapore Chinese Health Study, an ongoing prospective cohort study of 63 257 Singaporean Chinese men and women, 45–74 years of age at enrollment during 1993–1998 and were followed up for incidence of lung cancer for up to 25 years. Dietary vitamin B12 intake was derived from a validated food frequency questionnaire. Cox proportional hazard regression method was used to estimate hazard ratio and 95% confidence interval (CI) of lung cancer associated with dietary vitamin B12 intake with adjustment for multiple potential confounders.

Results

After a mean follow-up of 17.64 years, 2001 study participants developed lung cancer. High levels of vitamin B12 intake were associated with significantly increased risk of lung cancer (P
trend = 0.03). Compared with the lowest quintile, hazard ratios (95% CIs) of lung cancer for quintile 2, 3, 4, and 5 of vitamin B12 intake were 1.09 (0.95–1.25), 1.11 (0.96–1.28), 1.11 (0.97–1.29) and 1.18 (1.03–1.35), respectively. This positive association was more apparent in men than in women, in adenocarcinoma patients, or in participants with equal or less than 2 years follow-up than those with longer duration of follow-up.

Conclusion

Higher intake of dietary vitamin B12 was associated with increased risk of lung cancer. This highlights the potential harmful effect of vitamin B12 supplementation for lung cancer.
Knowledge, attitude, preventive practices and utilization of cervical cancer screening among women in Nepal: a community-based cross-sectional study
Authors: Shrestha Aamod Dhoj , Gyawali Bishal , Shrestha Archana , Shrestha Sadeep , Neupane Dinesh , Ghimire Sarita , Campbell Christine , Kallestrup Per
Published: February 2021

Background

Cervical cancer continues to be a global public health concern and a leading cause of cancer deaths among Nepalese women. In spite of the availability of screening and treatment services in Nepal, the utilization of screening has been low. This study investigated knowledge, attitude, preventive practices and utilization of cervical cancer screening among women in a semi-urban area of Pokhara Metropolitan City of Nepal.

Methods

A community-based cross-sectional survey was carried out among 729 women 30–60 years of age, between April and June 2019. Participants were selected by systematic random sampling, and a door-to-door home visit was conducted for data collection. A pretested interviewer-administered Nepali questionnaire was used to collect information on sociodemographic variables, knowledge, attitude and preventive practices regarding cervical cancer screening.

Results

The mean age of the participants was 45.9 years (SD ±7.7); the majority were married (86.7%). Among the participants, 44.9% were ever screened for cervical cancer. However, only 10.4% of participants received timely repeated screening for cervical cancer. The median knowledge score achieved by participants was 2.0 [interquartile range (IQR) 1–4] on a scale of maximum score 36, the median attitude score was 31.0 (IQR 29–32) on a scale of 40 and the median preventive practice score was 3.0 (IQR 3–4) on a scale of five.

Conclusion

This study showed low knowledge and low utilization of cervical cancer screening among women in Nepal. We recommend a community-based educational intervention to educate and empower women to increase knowledge and utilization of cervical cancer screening.
Genetic polymorphisms of FCGR2A, ORAI1 and CD40 are associated with risk of lung cancer
Authors: He Jinxi , Yu Liang , Qiao Zhixiong , Yu Bo , Liu Yang , Ren Hong
Published: February 2021

FCGR2A, ORAI1 and CD40 are all involved in the immune and inflammatory responses in the human body, whereas its association with lung cancer is still unclear. This study aimed to investigate the effects of polymorphisms in these genes on the susceptibility to lung cancer. Six candidate single nucleotide polymorphisms (SNPs) were genotyped using a MassARRAY platform in a discovery cohort, including 400 lung cancer patients and 400 healthy controls, and validated in a replication cohort, including 529 lung cancer cases and 532 controls. Comparing the allele frequency distributions, we found that the rs1801274-G, rs511278-T and rs1883832-T were risk alleles for lung cancer (P < 0.05), whereas the minor allele of rs12320939-T was a protective allele for the disease (P = 0.037). Comparing the genotype frequency distributions, we found that rs1801274-GG, rs511278-CT and of rs1883832-TT were risk genotype for lung cancer (P < 0.05). Genetic model analysis showed that the rs1801274 A>G was correlated with an elevated risk of lung cancer in recessive and log-additive models (P < 0.05); rs511278 C>T exhibited an increased risk of disease in dominant and log-additive models (P < 0.05); rs1883832 C>T had a strong relationship with risk of disease in all three models (P < 0.001), whereas rs12320939 G>T was correlated to a reduced risk of disease in recessive and log-additive models (P < 0.05). Finally, the association between the above SNPs and lung cancer risk was validated in a replication cohort (P < 0.05). These results shed new light on the association between immune-related genes and risk of lung cancer, and might be useful for the identification of high-risk individuals.
The efficacy of immunotherapy for in-transit metastases of melanoma: an analysis of randomized controlled trials
Authors: Olofsson Bagge Roger , Ny Lars , Ascierto Paolo A. , Hodi F. Stephen , Larkin James , Robert Caroline , Schachter Jacob , Weber Jeffrey S. , Long Georgina V. , van Akkooi Alexander C.J.
Published: February 2021

Nearly 10% of patients with high-risk early-stage melanoma will develop satellite or in-transit metastases (ITM), classified as stage III disease similar to lymph node metastases. The pivotal registration trials of the CTLA-4 antibody ipilimumab, and the PD-1 antibodies nivolumab and pembrolizumab, also included patients with unresectable stage III disease. However, there has been no analysis of patients with ITM, and anecdotal retrospective small series have indicated a potential lesser effect. This study aimed to identify patients with unresectable ITM within the randomized trials, and to determine response, progression-free survival and overall survival. The pivotal phase III randomized intervention trials that included melanoma patients with ITM, with or without nodal metastasis, and were treated with ipilimumab, nivolumab or pembrolizumab was identified. The datasets from each trial were then searched to identify the specific details of the investigated patient population for a pooled analysis. The primary endpoint was complete response rate. Seven trials that included stage III patients, and with accessible datasets, were identified. There was a total of 4711 patients, however, no patients with ITM could be identified, as this data was not captured by the case report forms. Evidence from prospective clinical trials on the use of immunotherapy in patients with ITM is lacking. We recommend pooling data from multiple institutions to examine efficacy of available drug therapies in this patient population, but more importantly, prospective clinical trials of locoregional treatments with or without systemic drug therapies are required.
Immunohistochemistry analysis reveals lysyl oxidase-like 3 as a novel prognostic marker for primary melanoma
Authors: Zhang Xue , Su Ming-Wan , Cheng Yabin , Martinka Magdalena , Wang Gang , Huang Yuanshen , Li Lingling , Zhou Youwen
Published: February 2021

Lysyl oxidase-like 3 (LOXL3) is an extracellular enzyme involved in the synthesis of collagen and elastin, and it has been reported to promote melanoma cell proliferation and invasion in vitro. However, the expression level of LOXL3 at different stages of melanocytic lesions and the role of LOXL3 in melanoma pathogenesis remain unknown. Immunohistochemical staining of LOXL3 in a tissue microarray of 373 biopsies at different melanocytic stages was conducted. The correlation between LOXL3 expression and patient survival was examined using Kaplan–Meier survival analysis. Univariate and multivariate Cox regression analyses were conducted to study the hazard ratios. The tissue microarray study revealed that stronger expression of LOXL3 protein was found at more advanced melanocytic stages (P < 0.0001; χ
2 test). Increased LOXL3 expression was associated with enhanced tumor thickness and mitosis. Survival analysis showed significantly worsened prognosis in primary melanoma patients when the LOXL3 expression level was higher (P = 0.043; log-rank test). Multivariate Cox regression analysis further showed that LOXL3 expression is a prognostic factor for primary melanoma patient survival (P = 0.04). LOXL3 expression is positively correlated with tumor progression and invasion, and its overexpression is associated with worse prognosis of primary melanoma patients. LOXL3 can serve as a prognostic marker to help identify primary melanoma patients at higher risks of death.
Outcomes of Ramucirumab Plus Paclitaxel Among Patients With Previously Treated Metastatic Gastric/Lower Esophageal Cancer
Authors: Abdel-Rahman Omar , Mulder Karen , Easaw Jacob
Published: February 2021

Objective:

The objective of this study was to review real-world patterns of chemotherapy utilization among patients with metastatic gastric/lower esophageal adenocarcinoma with particular focus on the use of ramucirumab plus paclitaxel in previously treated patients.

Methods:

This is a retrospective, registry-based study using datasets from Alberta Cancer Registry and other provincial databases in Alberta, Canada. Multivariable logistic regression analysis was used to identify factors associated with palliative chemotherapy use. Among patients who received >1 line of chemotherapy, Kaplan-Meier survival estimates were used to compare outcomes according to ramucirumab plus paclitaxel use. Multivariable Cox regression analysis was then used to identify factors associated with overall survival (OS) in this cohort.

Results:

A total of 1590 patients were included (including 1070 gastric patients and 520 lower esophageal patients). The following factors were associated with use of palliative chemotherapy: younger age (odds ratio with increasing age: 0.95; 95% confidence interval [CI]: 0.94-0.95), and lower Charlson Comorbidity Index (odds ratio with increasing index: 0.82; 95% CI: 0.74-0.91). Within the subcohort of patients who received >1 line of chemotherapy, use of ramucirumab/paclitaxel was associated with better OS (P=0.033). Multivariable Cox regression analysis suggested that the following factors are associated with better OS: use of ramucirumab/paclitaxel (hazard ratio [HR]: 1.56; 95% CI: 1.07-2.29) and living within urban zones including Calgary or Edmonton zones (vs. Northern zone) (HR for Calgary zone vs. Northern zone: 0.44; 95% CI: 0.23-0.85; HR for Edmonton zone vs. Northern zone: 0.41; 95% CI: 0.22-0.77).

Conclusions:

Use of paclitaxel/ramucirumab combination beyond first-line treatment is associated with improved OS among patients with metastatic gastric/lower esophageal adenocarcinoma in this real-world study. Further work is needed to reduce disparity in our health care system between individuals living in rural versus urban areas.
Long-acting injectable HIV therapies: the next frontier: Republication
Authors: Thornhill John , Orkin Chloe
Published: February 2021

Purpose of review

There has been significant development of long-acting injectable therapy for the management of HIV in recent years that has the potential to revolutionise HIV care as we know it. This review summarises the data and outlines the potential challenges in the field of long-acting antiretroviral therapy (ART).

Recent findings

In recent years, monthly and two monthly long-acting injectable ART in the form of cabotegravir and rilpivirine has shown safety and efficacy in large-scale phase 3 randomised control trials. Also, agents with novel mechanisms of action, such as Lenacapavir, have been tested in early-phase studies and are currently being tested in phase 2-3 clinical trials; if successful, this may allow six-monthly dosing schedules.

However, despite evidence that suggests that these therapies are efficacious and acceptable to patients, the challenge of integrating these agents into our current healthcare infrastructure and making these novel agents cost-effective and available to the populations most likely to benefit remains. The next frontier for long-acting therapy will be to introduce these agents in a real-world setting ensuring that the groups most in need of long-acting therapy are not left behind.
Potential and demonstrated impacts of the COVID-19 pandemic on sexually transmissible infections: Republication
Authors: Ogunbodede Olaitan T. , Zablotska-Manos Iryna , Lewis David A.
Published: February 2021

Purpose of review

This review considers the potential and demonstrated impacts of SARS-CoV-2 on the sexually transmissible infection (STI)/HIV transmission.

Recent findings

COVID-19 increases the vulnerability of those at highest risk of acquiring STI/HIV. Altered health-seeking behaviour, reductions in STI/HIV clinic capacity, service disruptions and redeployment of human resources to assist COVID-19 control efforts have impacted on STI/HIV control programmes. Reports of reduced STI incidence are emerging, but it is hard to determine whether this is real or due to decreased testing during COVID-19 lockdown periods. Fear of COVID-19 and implemented control measures have altered STI/HIV transmission dynamics. Sexual health services adapted to the pandemic by reducing face-to-face patient encounters in favour of telehealth and mail-based initiatives as well as more stringent triage practice. Many sexual health and HIV treatment services now operate at reduced capacity and experience ongoing service disruptions, which necessarily translates into poorer outcomes for patients and their communities.

In the short-term, COVID-19 related sexual behaviour change is driving STI/HIV transmission downwards. However, the impacts of the global COVID-19 response on sexual health-seeking behaviour and STI/HIV services threaten to drive STI/HIV transmission upwards. Ultimately, the expected rebound in STI/HIV incidence will require an appropriate and timely public health response.

Video abstract

http://links.lww.com/COID/A31.
Cyanoacrylate Closure of Small Saphenous Vein Insufficiency
Authors: Cho Sungsin , Joh Jin Hyun
Published: February 2021

BACKGROUND

As minimally invasive techniques were issued, endovenous thermal ablations have emerged. However, the thermal-associated complication has been reported in the treatment of small saphenous vein (SSV) insufficiency, such as sural nerve injury. Recently introduced cyanoacrylate closure (CAC) is a nonthermal modality, so this thermal-associated complication can be avoided.

OBJECTIVE

This retrospective study analyzed the feasibility, safety, and 2-year results of CAC for treating SSV insufficiency, particularly the incidence of sural nerve injury.

MATERIALS AND METHODS

One hundred sixty-three SSV insufficiencies in 128 patients were treated with CAC were reviewed. Pain, venous severity, and quality of life (QoL) scores were evaluated. Postoperative duplex scanning also evaluated anatomical and clinical success rates.

RESULTS

The mean patient age was 56.8 years. The initial technical success rate was 100%. The occlusion rate after 2 years was 96.3%. Pain, venous severity, and QoL scores were improved significantly from 2.4 to 0.0, 4.39 to 0.47, and 11.95 to 2.69, respectively, before and 2 years after CAC. No major complications were observed, such as sural nerve injury.

CONCLUSION

Cyanoacrylate closure for the ablation of SSV insufficiency could be a great alternative to endothermal ablation with an excellent success rate and shorter procedure time.
Quality of Patient Information on Lipofilling in the Internet
Authors: Spennato Stefano , Zuk Grzegorz , Ghamin Wahid , Raptis Dimitri A. , Palma Adrian F.
Published: February 2021

BACKGROUND

Patients interested in aesthetic surgery actively search the Internet, a source that contains important but biased information.

OBJECTIVE

The aim of this study was to assess the quality of patient information on autologous fat grafting available on the Internet.

MATERIALS AND METHODS

The quantitative and qualitative assessment of websites was based on a modified Ensuring Quality Information for Patients tool (EQIP-36 items). Websites were identified through the most popular search engines (Google, Yahoo, Bing, Ask, and AOL).

RESULTS

After duplicate and irrelevant sources were excluded, 608 remaining websites were assessed. Only 164 websites addressed >17 of the 36 items. Scores tended to be higher for academic centers and professional societies than for websites developed by private practitioners. The EQIP score achieved by websites ranged between 0 to 28, with a median value of 14 points.

CONCLUSION

The quality of patient information on lipofilling available on the Internet is very poor, and research on existing websites reveals substantial shortcomings. There is an urgent need for sources offering superior quality and unbiased information on lipofilling for patients who intend to undergo this procedure.
Predicting Negative Outcomes of Cryolipolysis in Patients With and Without Raynaud Disease
Authors: Yanes Daniel , Sawaya Jennifer , Wanner Molly , Avram Mathew
Published: February 2021

BACKGROUND

Cryolipolysis is an effective means of noninvasive fat reduction. There are numerous relative contraindications to cryolipolysis including scars, hernias, and cold-related disorders such as Raynaud disease, because cryolipolysis has a theoretical risk of exacerbating these conditions.

OBJECTIVE

To examine predictors of negative outcomes of cryolipolysis, especially as it pertains to safety of cryolipolysis in patients with Raynaud disease.

MATERIALS AND METHODS

A retrospective review of patients who received consultation for cryolipolysis was conducted and analyzed.

RESULTS

Patients with Raynaud disease did not experience any exacerbations of their underlying condition after cryolipolysis. Side effects in all patients, regardless of medical history, were mild, temporary, and not associated with any predisposing factors.

CONCLUSION

Cryolipolysis seems to be safe in patients with mild–moderate Raynaud disease.
Revisiting the Safety of Prostaglandin Analog Eyelash Growth Products
Authors: Steinsapir Kenneth D. , Steinsapir Samantha M.G.
Published: February 2021

BACKGROUND

The FDA approved bimatoprost ophthalmic solution 0.03% for treatment of eyelash hypotrichosis in 2008. Consumer concern persists regarding potential side effects of this product.

OBJECTIVE

To identify gaps in the safety information associated with the use of prostaglandin eyelash growth products.

MATERIALS AND METHODS

Literature searches were performed using PubMed, Embase, and Nexis Uni databases without restriction to publication date, language, or study setting.

RESULTS

The literature pertaining to bimatoprost for treatment of eyelash hypotrichosis is dominated by industry-sponsored clinical trials. Study design choices create gaps in our understanding of the clinical safety of these products.

CONCLUSION

Because of study design choice, clinical trials of bimatoprost for eyelash growth may have systematically underreported the incidence of drug application discomfort and prostaglandin-associated periorbitopathy. The risk of increased iris pigmentation remains inadequately investigated. Consequently, there is an ongoing need to educate and monitor patients who choose to use these products.
Modified Jessner's Solution Combined With Trichloroacetic Acid 20% Versus Glycolic Acid 70% Combined With Trichloroacetic Acid 20% in the Treatment of Melasma
Authors: Abdel-Majid Ensaf M. , Helmy Ereny R. , Abdel Motaleb Amira A.
Published: February 2021

BACKGROUND

Melasma is an acquired challenging pigmentary skin problem, which commonly affects the face. A wide range of therapeutic modalities is available, yet none is satisfactory.

OBJECTIVE

To compare efficacy and safety of trichloroacetic acid (TCA) 20% peeling with either modified Jessner's solution (MJs) or with glycolic acid (GA) 70% peeling in the treatment of melasma.

PATIENTS AND METHODS

Thirty adult Egyptian women with melasma were recruited in the study. After cleansing the face, MJs was applied on one side of the face and GA 70% on the other side. Then, TCA 20% was applied in one uniform coat on both sides of the face. Assessment of the clinical response was guided by calculating the melasma area, severity index (MASI), modified MASI, and hemi-MASI scores before and after the end of treatment.

RESULTS

Both combinations showed significant reduction in MASI, modified MASI, and hemi-MASI scores (p value = .000, for each). Moreover, the hemi-MASI score after MJs and TCA20% showed a significant decrease compared with GA70% and TCA20% (p value = .013).

CONCLUSION

Both modalities are successful, safe options for treating melasma. Moreover, combining MJs with TCA 20% is more efficacious.
Polidocanol Sclerotherapy for the Treatment of Pyogenic Granuloma in Children
Authors: Li Jing , Wu Changhua , Song Dan , Wang Liang , Guo Lei
Published: February 2021

BACKGROUND

Pyogenic granuloma (PG) is a benign vascular lesion that is commonly observed in the skin and mucosa. Sclerotherapy is the first-line conservative treatment option for PG.

OBJECTIVE

This retrospective study aimed to evaluate the efficacy of sclerotherapy with 1.0% polidocanol for the treatment of PG.

MATERIALS AND METHODS

All patients who were clinically diagnosed with PG consecutively at the Pediatric Outpatient Service of Qilu Children's Hospital of Shandong University from March 2018 to October 2019 received sclerotherapy with 1.0% polidocanol.

RESULT

The procedure resulted in the complete excision of PG, with inconspicuous scars. The procedure was well-tolerated, and recurrence was not observed. Allergic reactions, cutaneous necrosis, and pigmentary changes were not observed.

CONCLUSION

Sclerotherapy with 1.0% polidocanol is considered an effective treatment for PGs in children. Early treatment was associated with a more favorable outcome.
Efficacy and Clinical Outcomes of Bleomycin in the Treatment of Lymphangiomas: A Multicenter Experience
Authors: Bawazir Osama A. , Bawazir Razan , Bawazir Abdullah , Kausar Nadeem , Said Hanan
Published: February 2021

BACKGROUND

Bleomycin sclerotherapy became a popular nonsurgical option for the management of lymphangiomas. However, its efficacy has not been thoroughly evaluated. The purpose of this study was to assess the clinical outcomes and the effectiveness of bleomycin injection for the treatment of lymphangioma.

METHODS

This retrospective study was conducted in 4 centers and included 47 infants and children. All patients had bleomycin sclerotherapy between November 2005 and September 2020. Men presented 53.2% of the study sample (n = 25), and the most common site was the head and neck (n = 29, 61.7%).

RESULTS

Two injections were required in 11 patients (23.4%), and 7 patients (14.9%) required 3 or more injections. Excellent response was achieved in 63.8% (n = 30), 14 patients (29.8%) had a good response, and 4 had a poor response (8.5%). There was no difference in the response according to the site of the lesion (p = .75). The most frequent complication was recurrence (n = 11, 23.4%), and swelling occurred in 5 patients (10.6%). No patient had facial or phrenic nerve palsy or hoarseness. Two patients had persistent pain, and 2 had an infection (4.3%).

CONCLUSION

Intralesional bleomycin injection could be an effective therapy for lymphangiomas. The procedure has a low complication profile, and long-term study is recommended to evaluate the systemic and late bleomycin injection complications.
To Estimate or to Forecast? Lessons From a Comparative Analysis of Four Bayesian Fitting Methods Based on Nonparametric Models
Authors: Goutelle Sylvain , Alloux Céline , Bourguignon Laurent , Van Guilder Michael , Neely Michael , Maire Pascal
Published: February 2021

Using pharmacokinetic (PK) models and Bayesian methods in dosing software facilitates the analysis of individual PK data and precision dosing. Several Bayesian methods are available for computing Bayesian posterior distributions using nonparametric population models. The objective of this study was to compare the performance of the maximum a posteriori (MAP) model, multiple model (MM), interacting MM (IMM), and novel hybrid MM(HMM) in estimating past concentrations and predicting future concentrations during therapy. Amikacin and vancomycin PK data were analyzed in older hospitalized patients using 2 strategies. First, the entire data set of each patient was fitted using each of the 4 methods implemented in BestDose software. Then, the 4 methods were used in each therapeutic drug monitoring occasion to estimate the past concentrations available at this time and to predict the subsequent concentrations to be observed on the next occasion. The bias and precision of the model predictions were compared among the methods. A total of 406 amikacin concentrations from 96 patients and 718 vancomycin concentrations from 133 patients were available for analysis. Overall, significant differences were observed in the predictive performance of the 4 Bayesian methods. The IMM method showed the best fit to past concentration data of amikacin and vancomycin, whereas the MM method was the least precise. However, MM best predicted the future concentrations of amikacin. The MAP and HMM methods showed a similar predictive performance and seemed to be more appropriate for the prediction of future vancomycin concentrations than the other models were. The richness of the prior distribution may explain the discrepancies between the results of the 2 drugs. Although further research with other drugs and models is necessary to confirm our findings, these results challenge the widely accepted assumption in PK modeling that a better data fit indicates better forecasting of future observations.
Performance Evaluation of Warfarin Dose Prediction Algorithms and Effects of Clinical Factors on Warfarin Dose in Chinese Patients
Authors: Gao Weiqi , Li Zhihong , Chen Weihong , Zhang Shuqiu
Published: February 2021

Background:

The clinical utility of warfarin dose prediction algorithms remains controversial, our purpose is to evaluate the performance of warfarin dose prediction algorithms and the effects of clinical factors on warfarin dose in Chinese patients.

Methods:

Clinical data of 217 patients who received warfarin treatment were used to assess 6 warfarin dose prediction algorithms (OHNO, IWPC [International Warfarin Pharmacogenetics Consortium], HUANG, KIM, BRESS, and MIAO). The predicted dose (PD) was compared with the warfarin optimal dose (WOD, defined as the dose that maintains the international normalized ratio within the target range of 2.0–3.0). A multiple regression analysis with WOD as the dependent variable was performed to evaluate the effects of clinical factors on warfarin dose.

Results:

The mean absolute error analysis ranked the predictive accuracies of the algorithms as OHNO > IWPC > HUANG > KIM > BRESS > MIAO. Stratified analysis indicated that HUANG most accurately predicted that patients required lower WODs (≤3 mg/d), whereas OHNO was the most effective in predicting medium WODs (3–5 mg/d). KIM was effective in predicting high WODs (>5 mg/d). Multiple linear regression analysis showed that VKORC1 (rs9923231) and body mass index were significantly positively correlated with WOD, whereas concurrent atrial fibrillation status, CYP2C9*3 (rs1057910), and sex were significantly negatively correlated with WOD.

Conclusions:

In Chinese patients, OHNO should be given priority during the prediction and selection of warfarin dose. When using OHNO to predict warfarin dose (≤3 mg/d or >5 mg/d), HUANG or KIM algorithms can provide precise predictions. At the same time, physicians should pay close attention to clinical factors, such as VKORC1 (rs9923231), concurrent atrial fibrillation status, CYP2C9*3 (rs1057910), body mass index, and sex, to improve warfarin dose adjustment strategies in Chinese patients.