bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive Impairment after Lacunar Stroke and the Risk of Recurrent Stroke and Death
Authors: Kwan Abraham , Wei Jingkai , Dowling N. Maritza , Power Melinda C. , Nadareishvili Zurab ,   SPS3 Study Group
Published: March 2021

Introduction: Patients with poststroke cognitive impairment appear to be at higher risk of recurrent stroke and death. However, whether cognitive impairment after lacunar stroke is associated with recurrent stroke and death remains unclear. We assessed whether global or domain-specific cognitive impairment after lacunar stroke is associated with recurrent stroke and death. Methods: We considered patients from the Secondary Prevention of Small Subcortical Strokes (SPS3) trial with a baseline cognitive exam administered in English by certified SPS3 personnel, 14–180 days after qualifying lacunar stroke. We considered a baseline score of ≤86 on the Cognitive Assessment Screening Instrument to indicate global cognitive impairment, <10 on the Clock Drawing on Command test to indicate executive function impairment, and domain-specific summary scores in the lowest quartile to indicate memory and nonmemory impairment. We used Cox proportional hazards models to estimate the association between poststroke cognitive impairment and subsequent risk of recurrent stroke and death. Results: The study included 1,528 participants with a median enrollment time of 62 days after qualifying stroke. During a mean follow-up of 3.9 years, 11.4% of participants had recurrent stroke and 8.2% died. In the fully adjusted models, memory impairment was independently associated with an increased risk of recurrent stroke (hazard ratio, 1.48; 95% confidence interval [95% CI]: 1.04–2.09) and death (hazard ratio, 1.87; 95% CI: 1.25–2.79). Global impairment (hazard ratio, 1.66; 95% CI: 1.06–2.59) and nonmemory impairment (hazard ratio, 1.74; 95% CI: 1.14–2.67) were associated with an increased risk of death. Discussion/Conclusion: After lacunar stroke, memory impairment was an independent predictor of recurrent stroke and death, while global and nonmemory impairment were associated with death. Cognitive screening in lacunar stroke may help identify populations at higher risk of recurrent stroke and death.
Whole-Exome Sequencing Solved over 2-Decade Kidney Disease Enigma
Authors: Isaranuwatchai Suramath , Chanakul Ankanee , Ittiwut Chupong , Srichomthong Chalurmpon , Shotelersuk Vorasuk , Praditpornsilpa Kearkiat , Suphapeetiporn Kanya
Published: March 2021

Chronic kidney disease of unknown etiology (CKDu) has been a problem in renal practice as indefinite diagnosis may lead to inappropriate management. Here, we report a 54-year-old father diagnosed with CKDu at 33 years old and his 8-year-old son with steroid-resistant nephrotic syndrome. Using whole-exome sequencing, both were found to be heterozygous for c.737G>A (p.Arg246Gln) in LMX1B. The diagnosis of LMX1B-associated nephropathy has led to changes in the treatment plan with appropriate genetic counseling. The previously reported cases with this particular mutation were also reviewed. Most children with LMX1B-associated nephropathy had nonnephrotic proteinuria with normal renal function. Interestingly, our pediatric case presented with steroid-resistant nephrotic syndrome at 8 years old and progressed to ESRD requiring peritoneal dialysis at the age of 15 years. Our report emphasized the need of genetic testing in CKDu for definite diagnosis leading to precise management.
Vascular Permeability: Regulation Pathways and Role in Kidney Diseases
Authors: Cai Anxiang , Chatziantoniou Christos , Calmont Amélie
Published: March 2021

Background: Vascular permeability (VP) is a fundamental aspect of vascular biology. A growing number of studies have revealed that many signalling pathways govern VP in both physiological and pathophysiological conditions. Furthermore, emerging evidence identifies VP alteration as a pivotal pathogenic factor in acute kidney injury, chronic kidney disease, diabetic kidney disease, and other proteinuric diseases. Therefore, perceiving the connections between these pathways and the aetiology of kidney disease is an important task as such knowledge may trigger the development of novel therapeutic or preventive medical approaches. In this regard, the discussion summarizing VP-regulating pathways and associating them with kidney diseases is highly warranted. Summary: Major pathways of VP regulation comprise angiogenic factors including vascular endothelial growth factor/VEGFR, angiopoietin/Tie, and class 3 semaphorin/neuropilin and inflammatory factors including histamine, platelet-activating factor, and leukocyte extravasation. These pathways mainly act on vascular endothelial cadherin to modulate adherens junctions of endothelial cells (ECs), thereby augmenting VP via the paracellular pathway. Elevated VP in diverse kidney diseases involves EC apoptosis, imbalanced regulatory factors, and many other pathophysiological events, which in turn exacerbates renal structural and functional disorders. Measures improving VP effectively ameliorate the diseased kidney in terms of tissue injury, endothelial dysfunction, kidney function, and long-term prognosis. Key Messages: (1) Angiogenic factors, inflammatory factors, and adhesion molecules represent major pathways that regulate VP. (2) Vascular hyperpermeability links various pathophysiological processes and plays detrimental roles in multiple kidney diseases.
Phytotherapeutische Ansätze zur Behandlung des laryngopharyngealen Reflux in der HNO-Praxis
Authors: Zürcher Barbara
Published: March 2021

Der gastroösophageale Reflux, auch GERD genannt (gastroesophageal reflux disease) ist mit einer Prävalenz von 20–30% der erwachsenen Bevölkerung ein weit verbreitetes Problem. Davon abzugrenzen ist der häufig in der HNO-Praxis anzutref­fende laryngopharyngeale Reflux (LPR), bei dem es sich um eine durch den Magensäurereflux bedingte Entzündung der oberen Atemwege handelt. Die Unterschiede im klinischen Bild charakterisieren die widersprüchliche Beziehung der beiden klinischen Entitäten und erschweren die Diagnosestellung. Darüber hinaus muss ein besonderes Augenmerk auf Beschwerden des Magen- und Darmtrakts gelegt und deren Behandlung nicht vernachlässigt werden. Neben diätetischen Ratschlägen zählen einige pflanzliche Arzneimittel zu den Therapieoptionen. Alginate, die ein Aufstossen verhindern, bewähren sich in der Praxis. Kombinationsarzneimittel aus der europäischen und tibetischen Tradition spielen eine wesentliche Rolle in der Behandlung, nicht nur des LPR sondern auch bei Verdauungsproblemen des oberen und unteren Verdauungstrakts, wie Reizmagen und Reizdarm.
Domestic Violence during the COVID-19 Pandemic in Portugal
Authors: Gama Ana , Pedro Ana Rita , de Carvalho Maria João Leote , Guerreiro Ana Esteves , Duarte Vera , Quintas Jorge , Matias Andreia , Keygnaert Ines , Dias Sónia
Published: March 2021

The measures implemented to combat the COVID-19 pandemic led populations to confinement at home, with increased risk of domestic violence due to extended shared time between victims and offenders. Evidence on domestic violence in times of pandemic is lacking. This study examines the occurrence of domestic violence, associated factors and help seeking during the COVID-19 pandemic. An online survey was conducted in Portugal between April and October 2020 by NOVA National School of Public Health. The survey was disseminated through partner networks, media, and institutions working within the scope of violence. Data were collected on the experience of domestic violence, and help seeking during the pandemic. In a total of 1,062 respondents, 146 (13.7%) reported having suffered domestic violence during the pandemic, including psychological (13.0%, n = 138), sexual (1.0%, n = 11), and physical (0.9%, n = 10) abuse. Overall, the lower the age, the more the reported domestic violence. Also, a higher proportion of participants who perceived difficulties to make ends meet during the pandemic reported domestic violence. Differences between women and men and across educational levels on reported domestic violence were not statistically significant. Bivariate logistic analyses showed that, among women, reported domestic violence was more likely among those with up to secondary education compared to higher education. Most of the victims did not seek help (62.3%), the main reasons being considering it unnecessary, that help would not change anything, and feeling embarrassed about what had happened. Only 4.3% of the victims sought police help. The most common reasons for not coming forward to form a complaint were considering the abuse was not severe and believing the police would not do anything. Our findings indicate that domestic violence during the COVID-19 pandemic was experienced by both sexes and across different age groups. There is a need for investing in specific support systems for victims of domestic violence to be applied to pandemic contexts, especially targeting those in more vulnerable situations and potentially underserved.
Programmed Death Ligand 1 Expression as a Prognostic Marker in Patients with Advanced Biliary Tract Cancer
Authors: Kim Hyera , Kim Jinchul , Byeon Seonggyu , Jang Kee-Taek , Hong Jung Yong , Lee Jeeyun , Park Se Hoon , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Kim Seung Tae
Published: March 2021

Background: Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients. Patients and Methods: We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score positivity. Results: Of the 186 patients, the primary tumor location was intrahepatic cholangiocarcinoma (IHCC) in 72 (38.7%), extrahepatic cholangiocarcinoma (EHCC) in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). Among all the patients, 53 (28.5%) had PD-L1 positivity. The median overall survival (OS) of patients with PD-L1 positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. OS and PFS were not statistically different between groups. In subgroup analysis, EHCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p = 0.002) and PFS (7.8 vs. 5.4 months, p = 0.005) than those who were PD-L1-positive. However, this finding was not reproduced in patients with IHCC or GB cancer. Conclusion: This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EHCC but not in patients with IHCC or GB cancer.
Dermatologic Research Potential of the Observational Health Data Sciences and Informatics (OHDSI) Network
Authors: Sivesind Torunn Elise , Runion Taylor , Branda Megan , Schilling Lisa M. , Dellavalle Robert P.
Published: March 2021

Background: The Observational Health Data Sciences and Informatics (OHDSI) network enables access to billions of deidentified, standardized health records and built-in analytics software for observational health research, with numerous potential applications to dermatology. While the use of the OHDSI has increased steadily over the past several years, review of the literature reveals few studies utilizing OHDSI in dermatology. To our knowledge, the University of Colorado School of Medicine is unique in its use of OHDSI for dermatology big data research. Summary: A PubMed search was conducted in August 2020, followed by a literature review, with 24 of the 72 screened articles selected for inclusion. In this review, we discuss the ways OHDSI has been used to compile and analyze data, improve prediction and estimation capabilities, and inform treatment guidelines across specialties. We also discuss the potential for OHDSI in dermatology – specifically, ways that it could reveal adherence to available guidelines, establish standardized protocols, and ensure health equity. Key Messages: OHDSI has demonstrated broad utility in medicine. Adoption of OHDSI by the field of dermatology would facilitate big data research, allow for examination of current prescribing and treatment patterns without clear best practice guidelines, improve the dermatologic knowledge base and, by extension, improve patient outcomes.
Clinical Impact of the Prognostic Nutritional Index as a Predictor of Outcomes in Patients with Stage II/III Gastric Cancer: A Retrospective Cohort Study
Authors: Okubo Keishi , Arigami Takaaki , Matsushita Daisuke , Tanaka Takako , Tsuruda Yusuke , Noda Masahiro , Sasaki Ken , Mori Shinichiro , Kurahara Hiroshi , Ohtsuka Takao
Published: March 2021

Background: The Japanese Gastric Cancer Treatment Guidelines recommend S-1 and S-1 plus docetaxel as postoperative chemotherapy for pathological stage II and III gastric cancer (GC). There is currently no strategy for using chemotherapy to treat high-risk recurrent pathological stage II/III. Previous studies reported that the several nutritional, immunological, and inflammatory markers examined the association with clinical outcomes after surgery for GC. Methods: Ninety patients with GC (stage II, n = 48; stage III, n = 42) for whom gastrectomy was performed at our institution between November 2009 and September 2018 were examined. Nutritional, immunological, and inflammatory markers were calculated from blood samples within 1 week before surgery. Results: The prognostic nutritional index (PNI) status correlated with the pathological stage and disease recurrence after surgery (p = 0.015 and p < 0.0001, respectively). Thirty-three patients had disease recurrence after gastrectomy (stage II, n = 11; stage III, n = 22). The PNI was significantly lower in the recurrent group than in the non-recurrent group (p = 0.0003). The PNI correlated with overall survival and recurrence-free survival after gastrectomy (p = 0.0021 and p = 0.0001, respectively). A multivariate analysis identified the PNI as an independent prognostic factor (p = 0.006). Conclusion: The PNI may be useful for predicting the outcomes of patients with pathological stage II/III GC and may contribute to the selection of an appropriate adjuvant chemotherapy regimen.
Are Breast Cancer Nomograms Still Valid to Predict the Need for Axillary Dissection?
Authors: Madekivi Vilma , Karlsson Antti , Boström Pia , Salminen Eeva
Published: March 2021

Background: Nomograms can help in estimating the nodal status among clinically node-negative patients. Yet their validity in external cohorts over time is unknown. If the nodal stage can be estimated preoperatively, the need for axillary dissection can be decided. Objectives: The aim of this study was to validate three existing nomograms predicting 4 or more axillary lymph node metastases. Method: The risk for ≥4 lymph node metastases was calculated for n = 529 eligible breast cancer patients using the nomograms of Chagpar et al. [Ann Surg Oncol. 2007;14:670–7], Katz et al. [J Clin Oncol. 2008;26(13):2093–8], and Meretoja et al. [Breast Cancer Res Treat. 2013;138(3):817–27]. Discrimination and calibration were calculated for each nomogram to determine their validity. Results: In this cohort, the AUC values for the Chagpar, Katz, and Meretoja models were 0.79 (95% CI 0.74–0.83), 0.87 (95% CI 0.83–0.91), and 0.82 (95% CI 0.76–0.86), respectively, showing good discrimination between patients with and without high nodal burdens. Conclusion: This study presents support for the use of older breast cancer nomograms and confirms their current validity in an external population.
Non-Muscle Invasive Bladder Cancer with Variant Histology: Biological Features and Clinical Implications
Authors: Sanguedolce Francesca , Calò Beppe , Mancini Vito , Zanelli Magda , Palicelli Andrea , Zizzo Maurizio , Ascani Stefano , Carrieri Giuseppe , Cormio Luigi
Published: March 2021

Background: The most common bladder cancer (BC) histotype is pure urothelial carcinoma (UC), which may undergo divergent differentiation in some cases. Variant histology (VH) presents along variable morphologies, either single or combined between them or with pure UC. From a clinical standpoint, the vast majority of BC is diagnosed at non-invasive or minimally invasive stages, namely as non-muscle invasive BC (NMIBC). There is a wide range of therapeutic options for patients with NMIBC, according to their clinical and pathological features. However, current risk stratification models do not show optimal effectiveness. Evidence from the literature suggests that VH has peculiar biological features, and may be associated with poorer survival outcomes compared to pure UC. Summary: In order to describe the biological features and prognostic/predictive role of VH in NMIBC, and to discuss current treatment options, we performed a systematic literature search through multiple databases (PubMed/Medline, Google Scholar) for relevant articles according to the following terms, single and/or in combination: “non-muscle invasive bladder cancer,” “variant histology,” “micropapillary variant,” “glandular differentiation,” “squamous differentiation,” “nested variant,” “plasmacytoid variant,” and “sarcomatoid variant.” We extracted 99 studies including original articles, reviews, and systematic reviews, and subsequently analyzed data from 16 studies reporting on the outcome of NMIBC with VH. We found that the relative rarity of these forms as well as the heterogeneity in study populations and therapeutic protocols results in conflicting findings overall. Key Messages: The presence of VH should be taken into account when counseling a patient with NMIBC, since it may upgrade the disease to high-risk tumor and thus warrant a more aggressive treatment.
Triglycerides Mediate Body Mass Index and Nonalcoholic Fatty Liver Disease: A Population-Based Study
Authors: Xing Jie , Guan Xue , Zhang Qian , Chen Shuohua , Wu Shouling , Sun Xiujing
Published: March 2021

Introduction: Nonalcoholic fatty liver disease (NAFLD) is defined by the accumulation of triglycerides (TG). The body mass index (BMI) is associated with NAFLD. This large-scale cohort study was performed to evaluate and quantify the mediating effect of TG on the association between BMI and NAFLD. Methods: In total, 15,943 participants in the Kailuan Group were recruited between 2010 and 2014. The impact of TG on the association between BMI and NAFLD was determined through a mediation analysis. Results: BMI was an independent risk factor for incident NAFLD, with OR of 1.416 (95% CI 1.338–1.499) and 1.187 (95% CI 1.137–1.240) in the low-BMI and high-BMI groups, respectively (p < 0.001). The TG level was a risk factor for NAFLD in the high-BMI group, with an OR of 2.775 (95% CI 1.488–5.177; p = 0.001). Positive associations between BMI and the TG level remained in the 2 above mentioned groups after adjusting for confounders (β = 0.072 and 0.032; p < 0.001). The mediation analysis revealed that TG contributed to 26.050% of incident NAFLD in the high-BMI group (p = 0.01). Conclusion: A high BMI was an independent risk factor for incident NAFLD, and a high TG level was a risk factor in the high-BMI group (BMI ≥24). TG contributes about 25% to incident NAFLD in people with obesity.
Immunotherapy in HER2-Positive Breast Cancer: A Systematic Review
Authors: Kyriazoglou Anastasios , Kaparelou Maria , Goumas Georgios , Liontos Michael , Zakopoulou Roubini , Zografos Eleni , Zygogianni Anna , Dimopoulos Meletios Athanasios , Zagouri Flora
Published: March 2021

Introduction: The clinical outcome of HER2-positive breast cancer patients changed with the use of anti-Her therapies, though it still remains an aggressive and fatal disease. Implementation of immune checkpoint inhibitors in HER2-positive Breast cancer is a concept supported by the reported biological and preclinical data. Methods: We conducted a systematic review of the current literature involving immune checkpoint inhibitors alone or in combination with targeted therapies or chemotherapy finalized or running in HER2-positive breast cancer. Results: Twelve clinical trials and 2 case reports were identified in our study. Conclusion: The reported clinical trials highlight that checkpoint inhibition seems to be promising in metastatic, neoadjuvant, and adjuvant settings of HER2-positive breast cancer.
Relationship between Cyst Fluid Concentrations of Iron and Severity of Dysmenorrhea in Patients with Ovarian Endometrioma
Authors: Imanaka Shogo , Maruyama Sachiyo , Kimura Mai , Nagayasu Mika , Kawahara Naoki , Kobayashi Hiroshi
Published: March 2021

Objectives and Design: Endometriosis-related pain can be caused by anatomical distortions as well as environmental factors such as inflammation and oxidative stress. The aim of this study is to investigate the relationship between the severity of dysmenorrhea in patients with ovarian endometrioma (OMA) and cyst fluid (CF) concentrations of irons, including total iron, heme iron, and free iron. Method: Eighty-three patients who were histologically diagnosed with OMA were enrolled in the Department of Gynecology, Nara Medical University Hospital, between 2013 and 2019. The patients were divided into 4 groups according to the severity of dysmenorrhea: no pain, mild, moderate, and severe. Iron concentration was measured by the inductively coupled plasma optical emission spectrometry method. Results: There were no significant differences among the 4 groups in variables such as age at diagnosis, preoperative CA125, preoperative CA19-9, cyst size, and tumor laterality (unilateral or bilateral). There was a positive correlation between the severity of dysmenorrhea and total iron (p < 0.001) and heme iron (p = 0.016) concentrations. Multiple regression analyses revealed that the CF concentration of total iron (hazard ratio 18.75, 95% confidence interval: 2.26–155.35, p = 0.007) was a significant independent variable associated with the severity of dysmenorrhea. A receiver operating characteristic curve analysis showed that a total iron exceeding 290.8 mg/L was associated with severe dysmenorrhea with a sensitivity of 90.9% and a specificity of 65.7%. Limitations: This study excluded patients with adenomyosis, superficial endometriosis, or deep endometriosis, resulting in a smaller number of cases. Iron levels could not be compared to the endometriosis stage using the r-ASRM score. Conclusions: There is no clear evidence that iron predicts the severity of endometriosis-related pain. However, iron may be closely associated with dysmenorrhea.
The Effect of Saffron Consumption on Liver Function: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials
Authors: Karimi Elham , Farrokhzad Amirhosein , Darand Mina , Arab Arman
Published: March 2021

Background and Aims: The present systematic review and meta-analysis of randomized controlled trials aimed to determine the effects of saffron supplementation on liver function tests among adults. Methods: Electronic databases including PubMed, ISI Web of Science, and Scopus were searched up to January 2021. The risk of bias in individual studies was assessed using the Cochrane Collaboration tool. The overall estimates and their 95% CIs were calculated using random-effects models. Egger’s test and Begg’s rank-correlation were run to assess the presence of publication bias. p < 0.05 was considered statistically significant. Results: A total of 12 trials involving 608 participants were included in this systematic review and meta-analysis. Saffron supplementation had no significant effect on liver function tests including aspartate transaminase (AST) (weighted mean difference [WMD] = 0.23 U/L; 95% CI –2.22 to 2.69; p = 0.851; I2 = 74.0%), alanine aminotransferase (ALT) (WMD = –1.49 U/L; 95% CI –3.84 to 0.86; p = 0.213; I2 = 60.2%), and alkaline phosphatase (ALP) (WMD = –0.70 U/L; 95% CI –11.35 to 9.95; p = 0.898; I2 = 40.8%) compared to placebo. Conclusion: Based on what was discussed, it seems that saffron supplementation could not improve liver function tests including AST, ALT, and ALP among the adult population. Further clinical trials with larger sample size, longer duration, and higher doses of saffron should be conducted exclusively among patients with liver dysfunction to elucidate the beneficial role of saffron consumption on liver function.
Challenges in Predicting Cognitive Decline in Dementia with Lewy Bodies
Authors: Tsamakis Konstantinos , Mueller Christoph
Published: March 2021

Despite being the second most common form of neurodegenerative dementia, dementia with Lewy bodies (DLB) is under-recognized and carries a worse prognosis than other subtypes of the condition. Cognitive impairment is a cardinal feature of all types of dementia and DLB presents with a distinct profile with deficits in attention, executive function, and visuoperceptual abilities. This difference from Alzheimer’s disease and the common presence of neuropsychiatric symptoms may lead to challenges in predicting cognitive decline in this patient population. Firstly, the diagnosis of DLB is often delayed in clinical practice leading to variability from which time point in the disease course cognitive decline is measured. Secondly, the most frequently used measurement tools for cognitive difficulties focus on memory and naming rather than the domains affected by DLB. While there is now largely a consensus which tools are useful in diagnosing DLB, their validity in assessing deteriorating cognition is less clear. Thirdly, the presence of fluctuating cognition, the propensity to develop delirium episodes, as well as difficulties in distinguishing the two entities in clinical practice make it difficult to predict the disease course. Sleep disturbances are likely to influence cognitive decline but require further study in patients within established DLB. Fourthly, as in most cases of dementia, neuropathological comorbidities are frequently present in DLB. While the influence of Alzheimer’s pathology on cognitive decline in DLB is comparatively well understood, the impact of other pathologies remains unclear. The recent definition of research criteria for mild cognitive impairment in DLB could facilitate earlier diagnosis and more structured follow-up. Assessment tools measuring cognitive domains predominantly affected in DLB need to be more consistently used in longitudinal studies and clinical practice, as well as concurrent measures of fluctuations in cognition. Greater availability of biomarkers and digital healthcare solutions can play an important role in enabling more accurate monitoring and prediction of cognitive decline in DLB.
A Mapping Literature Review of Medical Cannabis Clinical Outcomes and Quality of Evidence in Approved Conditions in the USA from 2016 to 2019
Authors: Jugl Sebastian , Okpeku Aimalohi , Costales Brianna , Morris Earl J. , Alipour-Haris Golnoosh , Hincapie-Castillo Juan M. , Stetten Nichole E. , Sajdeya Ruba , Keshwani Shailina , Joseph Verlin , Zhang Yahan , Shen Yun , Adkins Lauren , Winterstein Almut G. , Goodin Amie
Published: March 2021

In 2017, a National Academies of Sciences, Engineering, and Medicine (NASEM) report comprehensively evaluated the body of evidence regarding cannabis health effects through the year 2016. The objectives of this study are to identify and map the most recently (2016–2019) published literature across approved conditions for medical cannabis and to evaluate the quality of identified recent systematic reviews, published following the NASEM report. Following the literature search from 5 databases and consultation with experts, 11 conditions were identified for evidence compilation and evaluation: amyotrophic lateral sclerosis, autism, cancer, chronic noncancer pain, Crohn’s disease, epilepsy, glaucoma, human immunodeficiency virus/AIDS, multiple sclerosis (MS), Parkinson’s disease, and posttraumatic stress disorder. A total of 198 studies were included after screening for condition-specific relevance and after imposing the following exclusion criteria: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome definition, intervention definition, sample size, study setting, and reported effect size. Few completed randomized controlled trials (RCTs) were identified. Studies classified as systematic reviews were graded using the Assessing the Methodological Quality of Systematic Reviews-2 tool to evaluate the quality of evidence. Few high-quality systematic reviews were available for most conditions, with the exceptions of MS (9 of 9 graded moderate/high quality; evidence for 2/9 indicating cannabis improved outcomes; evidence for 7/9 indicating cannabis inconclusive), epilepsy (3 of 4 graded moderate/high quality; 3 indicating cannabis improved outcomes; 1 indicating cannabis inconclusive), and chronic noncancer pain (12 of 13 graded moderate/high quality; evidence for 7/13 indicating cannabis improved outcomes; evidence from 6/7 indicating cannabis inconclusive). Among RCTs, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic noncancer pain). The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions, and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions.
Impact of Sudarshan Kriya Yoga on Salivary pH: An Exploratory Pilot Study
Authors: Kanchibhotla Divya , Ingole Sumeet , Kulkarni Shashank , Saisudha Bharathi
Published: March 2021

Introduction: Saliva is increasingly used as a diagnostic tool as it is non-invasive, easily accessible, and less stressful compared to blood sampling. Saliva has a vital role in maintaining oral health. It is necessary for the salivary pH to be neutral in the oral cavity for the optimal functioning of its components. Stress has an effect on salivary pH. Objective: To study the effect of a mind-body intervention like Sudarshan Kriya yoga (SKY) on the salivary pH. Methods and Materials: An exploratory pilot study involving an open trial on 321 healthy individuals who were novice to SKY was conducted. The salivary pH was measured before and after a single 90-min session of SKY. Results: The salivary pH continued to be neutral after the intervention in the group that had initial neutral pH. There was a statistically significant shift of pH towards neutral in both the groups that had either acidic or alkaline pH initially. Conclusion: Mind-body interventions like SKY modulate the salivary pH to bring it to the range of optimal functioning. This pilot study provides information for future long-term studies that can be implemented with measures of anxiety and stress along with measuring other salivary biomarkers.
Pleuraempyem: Kryotherapie in der Thorakoskopie nutzen
Authors: Stanzel Franz
Published: March 2021

Surgical intervention is occasionally required for the treatment of pleural empyema. Semirigid thoracoscopy is a safe and successful surgical approach utilized by interventional pulmonologists, conventionally utilizing flexible forceps and suction as the main tools, but they can sometimes be inefficient for more complicated cases. In debriding a case of multiloculated empyema with semirigid thoracoscopy, we report the novel use of cryotherapy in clearing adhesions from the pleural cavity. We found using the cryoprobe to be more efficient than using forceps and suggest further investigation into its use in medical thoracoscopy.
Thyroid Disease Is Associated with Higher Age-Related Macular Degeneration Risk: Results from a Meta-Analysis of Epidemiologic Studies
Authors: Xu Ziming , Zhang Mei , Zhang Qing , Xu Tingjuan , Tao Liming
Published: March 2021

Background: Although epidemiologic studies have suggested that thyroid disease may be a risk factor for age-related macular degeneration (AMD), this finding is still controversial. Objectives: The aim of this meta-analysis was to investigate whether an association exists between thyroid disease and medication and AMD in epidemiologic studies. Methods: We searched PubMed, EMBASE, and Google Scholar from their inception to March 2020 for cross-sectional, case-control, and cohort studies that assessed thyroid function and AMD risk. Data from selected studies were extracted, and a meta-analysis was performed using fixed-effects or random-effects models. The statistical heterogeneity (I2) among studies and the possibility of publication bias were evaluated. If I2 >50%, a significant heterogeneity existed among studies, and a random-effects model was used to calculate the pooled RR. Otherwise, a fixed-effects model was performed. Results: A total of 13 epidemiologic studies that consisted of 7 thyroid disease and 7 thyroid medication studies were included. Statistically significant heterogeneity was observed in the study results (I2thyroid disease = 80.1%; I2thyroid medication = 69.0%). A significant positive association was found between thyroid disease and AMD, with an overall relative risk (RR) of 1.25 (95% CI: 1.02, 1.54). However, there was no statistical association between thyroid medication and AMD risk (pooled RR 1.26 [95% CI: 0.92–1.72]). Egger’s test indicated that there was no significant publication bias for thyroid disease (p = 0.889) or thyroid medication (p = 0.226). Conclusions: Our findings indicate that thyroid disease is associated with higher AMD risk. Thyroid disease prevention strategies may have a significant effect on the prevention of AMD and warrant further evaluation.
Inverted Internal Limiting Membrane Flap Technique versus Internal Limiting Membrane Peeling for Large Macular Holes: A Meta-Analysis of Randomized Controlled Trials
Authors: Yu Ji-Guo , Wang Jing , Xiang Yi
Published: March 2021

Background: Vitrectomy with internal limiting membrane (ILM) peeling is an effective surgical procedure for the treatment of macular holes (MHs). However, there is a possibility of poor postoperative anatomical closure with conventional ILM peeling for MHs larger than 400 μm. Therefore, a novel inverted ILM flap technique was developed for such cases. Objectives: This meta-analysis study was performed to evaluate and compare the anatomical and visual outcomes of the inverted ILM flap technique and ILM peeling in large MHs. Methods: The Cochrane Library, PubMed, and Embase databases were searched to identify randomized controlled trials (RCTs). The trial eligibility and risk of bias were assessed according to Cochrane review methods. The primary outcome measures included MH closure rate and postoperative visual acuity (VA). Subgroup analysis of postoperative VA based on follow-up time was also conducted. Pooled odds ratios (ORs), weighted mean difference (WMD), and 95% confidence intervals (CIs) were calculated. Statistical analysis was performed using RevMan 5.3 software. Results: Five RCTs with a total of 155 eyes in the inverted ILM flap group and 161 eyes in the ILM peeling group were included in this meta-analysis. Statistical meta-analysis revealed that the overall MH closure rate in the inverted ILM flap group was significantly higher than that in the ILM peeling group (OR = 3.10; 95% CI: 1.25–7.66; p = 0.01). The postoperative VA was significantly better in the inverted ILM flap group than the ILM peeling group (WMD = −0.14; 95% CI: −0.21 to −0.07; p = 0.0002). The subgroup meta-analysis indicated that the postoperative VA was significantly better in the inverted ILM flap group than the ILM peeling group (WMD = −0.17; 95% CI: −0.26 to −0.08; p = 0.0004) at the 3-month follow-up. However, no significant difference was observed between the 2 groups at the 6-month follow-up (WMD = −0.09; 95% CI: −0.20 to 0.02; p = 0.10). Conclusions: Vitrectomy with the inverted ILM flap technique showed a higher anatomical closure rate as well as visual gain – although only in the short term as no difference in visual recovery was found at the 6-month follow-up – than did ILM peeling in large MHs. The inverted ILM flap technique should be considered as a preferred and routine procedure for the treatment of patients with MHs larger than 400 µm.
Optical Coherence Tomography Biomarkers: Vitreous Status Influence in Outcomes for Diabetic Macular Edema Therapy with 0.19-mg Fluocinolone Acetonide Implant
Authors: Pessoa Bernardete , Ferreira André , Leite João , Figueira João , Meireles Angelina , Beirão João Melo
Published: March 2021

Background: The 0.19-mg fluocinolone acetonide (FAc) implant (ILUVIEN®; Alimera Sciences Ltd., Hampshire, UK) was approved for the treatment of vision impairment associated with chronic and refractory diabetic macular edema (DME). Objectives: To quantitatively assess functional and structural features in nonvitrectomized and vitrectomized DME patients after being treated with an FAc implant. Methods: Retrospective review of patients with DME receiving a single intravitreal injection of the FAc implant. The study was designed to analyze the presence of quantitative structural OCT biomarkers at baseline and 12 months after FAc therapy according to vitreous status. Results: A total of 41 eyes from 30 patients were included in this study. At 12 months after injection, vitrectomized patients had a lower central foveal thickness (p = 0.017) and fewer hyperreflective dots (p = 0.028) compared with nonvitrectomized. Thirty (73%) patients presented a significant functional improvement with 17 (42%) increasing at least 15 ETDRS letters. Overall, 22 (54%) eyes had a complete resolution of DME at the 12-month visit. Patients who needed additional therapy had a higher prevalence of subretinal fluid (42 vs. 3%, p = 0.005) at baseline. Conclusions: This study supports the effectiveness of the FAc implant and reports significant changes at 12 months after FAc injection.
Machine Learning to Predict Treatment in Oropharyngeal Squamous Cell Carcinoma
Authors: Karadaghy Omar A. , Shew Matthew , New Jacob , Bur Andrés M.
Published: March 2021

Objectives: This study seeks to (1) demonstrate how machine learning (ML) can be used for prediction modeling by predicting the treatment patients with T1–2, N0–N1 oropharyngeal squamous cell carcinoma (OPSCC) receive and (2) assess the impact patient, socioeconomic, regional, and institutional factors have in the treatment of this population. Methods: A retrospective cohort of adults diagnosed with T1–2, N0–N1 OPSCC from 2004 to 2013 was obtained using the National Cancer Database. The data was split into 80/20 distribution for training and testing, respectively. Various ML algorithms were explored for development. Area under the curve (AUC), accuracy, precision, and recall were calculated for the final model. Results: Among the 19,111 patients in the study, the mean (standard deviation) age was 61.3 (10.8) years, 14,034 (73%) were male, and 17,292 (91%) were white. Surgery was the primary treatment in 9,533 (50%) cases and radiation in 9,578 (50%) cases. The model heavily utilized T-stage, primary site, N-stage, grade, and type of treatment facility to predict the primary treatment modality. The final model yielded an AUC of 78% (95% CI, 77–79%), accuracy of 71%, precision of 72%, and recall of 71%. Conclusion: This study created a ML model utilizing clinical variables to predict primary treatment modality for T1–2, N0–N1 OPSCC. This study demonstrates how ML can be used for prediction modeling while also highlighting that tumor and facility realted variables impact the decision making process on a national level.
Inflammatory Cell Numbers in the Stomach of Japanese Subjects with Endoscopically Normal Mucosa without Helicobacter pylori Infection
Authors: Sumi Naoki , Haruma Ken , Kamada Tomoari , Suehiro Mitsuhiko , Manabe Noriaki , Akiyama Takashi , Shiotani Akiko , Yamanaka Yoshiyuki , Fujimoto Sohachi , Takao Toshihiro
Published: March 2021

Introduction: Since inflammatory cells, such as lymphocytes and plasma cells, normally inhabit the stomach, the border between normal and mild inflammation is difficult to visually determine using the updated Sydney system scale of gastritis. Additionally, eosinophils in the gastric mucosa must be counted to diagnose eosinophilic gastritis. We aimed to determine the normal number of inflammatory cells in patients with endoscopically normal mucosa and without Helicobacter pylori infections. Methods: We assessed patients aged 20–79 years, who had undergone upper gastrointestinal endoscopy at Kawasaki Medical School Hospital between January 2010 and December 2014. Inflammatory cells were counted in 1,000 μm2 fields of pyloric and fundic gland mucosal biopsy specimens. We finally included 325 (male, n = 141; female, n = 184; average age = 49.3 years) patients without inflammation who had H. pylori-negative endoscopic results and negative histological findings interpreted based on the updated Sydney System and the Kyoto classification of gastritis. Results: The average numbers of nucleated cells were 83.3 ± 14.2 and 65.4 ± 12.6/mm2 in the pyloric and fundic gland mucosae, respectively. Inflammatory cells were significantly more abundant in the pyloric mucosa than in the fundic gland mucosa (p < 0.05). Age and sex distribution did not significantly differ. Eosinophils were absent or scanty in the gastric mucosae of both glands in all patients. Conclusion: We determined the absolute values of inflammatory cells, including eosinophils, in normal mucosae of pyloric and fundic glands. These findings could be important in defining gastric mucosal inflammation, including eosinophilic gastritis diagnosis.
Characteristics and Outcomes of Endoscopies before and during the COVID-19 Pandemic in New York
Authors: Annadurai Vasantham , Blackett John W. , Freedberg Daniel , Hur Chin , Green Peter H.R. , Lebwohl Benjamin
Published: March 2021

Introduction: The COVID-19 pandemic drastically changed hospital workflows. This study aimed to characterize differences in gastrointestinal endoscopies in the New York metropolitan region before, during, and after the first wave of the pandemic. Methods: Across 3 hospitals, we compared demographics, indications, and yield of endoscopies before and after March 16, 2020, the date on which elective procedures were canceled, as well as a recovery period for 5 months after they were resumed. Results: A total of 9,401 procedures before and 332 procedures during the first wave were performed. Females comprised 57 and 44% of patients (p < 0.01), respectively. There was a decline in the proportion of Black (15 vs. 7%, p < 0.02) and Hispanic patients (29 vs. 16%, p < 0.02) undergoing outpatient procedures. There was a significant rise in urgent indications such as bleeding and jaundice. There was an increase in the diagnostic yield of all esophagogastroduodenoscopies for bleeding (p < 0.01) and of outpatient endoscopic ultrasounds for malignancy (p = 0.01), but no increase in yield of inpatient colonoscopy for bleeding. A review of 7,475 procedures during the recovery period showed a return to many nonurgent indications, but still showed decreased proportions of Hispanic and male patients compared to the prepandemic period. Discussion/Conclusion: Lower proportions of Black and Hispanic patients underwent outpatient endoscopies during and after the first wave. The proportion of procedures done for emergent indications and their diagnostic yield increased during the pandemic, suggesting a higher threshold to perform endoscopy. In resource-sparing conditions, clinicians should pay attention to thresholds to perform colonoscopy for bleeding and to racial disparities in outpatient healthcare access.
Fecal Lactoferrin Predicts Primary Nonresponse to Biologic Agents in Inflammatory Bowel Disease
Authors: Sorrentino Dario , Nguyen Vu Q. , Love Kim
Published: March 2021

Introduction: Fecal lactoferrin (FL) is a timely and accurate marker of inflammation in ulcerative colitis (UC) and Crohn’s disease (CD). The aim of this study was to verify whether FL can predict primary nonresponse (PNR) to biologic agents during induction. Methods: Retrospective outcome review in 27 patients (13 with CD and 14 with UC) tested for baseline FL and retested within a week after the first and second induction doses. Clinical/biochemical outcomes were evaluated at end of induction and at follow-up (3–24 months). Results: Compared to baseline, changes of the Harvey-Bradshaw (CD) and Partial Mayo Scoring (UC) indices at end of induction separated responders (18/27 or 67%) from nonresponders (9/17 or 33%). In all patients, the initial FL value at induction decreased compared to baseline, continuing to decrease after the following dose in clinical responders while bouncing back in the others. Models targeting the 2 consecutively decreased FL values or the second FL value compared to baseline or the second FL value compared to the first were able to accurately predict response at end of induction. Follow-up assessment confirmed clinical remission in initial responders (with FL values reduced on the average by 94 ± 10% compared to baseline). Conclusions: In CD and UC patients during induction with biologic agents, early FL measurements accurately separate clinical responders from those experiencing PNR. The method described here offers several potential advantages over other strategies to assess and manage these patients.
Characteristics and Healthcare Costs in the Aging Hepatitis B Population of Japan: A Nationwide Real-World Analysis
Authors: Yotsuyanagi Hiroshi , Kurosaki Masayuki , Yatsuhashi Hiroshi , Lee I-Heng , Ng Alvin , Brooks-Rooney Craig , Nguyen Mindie H.
Published: March 2021

Introduction: Advancing age, comorbidity, and financial burden have been observed in chronic hepatitis B (CHB) patients globally. As Japan is leading the world in aging demographics, similar real-world data are urgently needed for its CHB population to inform all stakeholders. Methods: This cross-sectional study characterized the demographics, comorbidities, and healthcare costs of a large Japanese real-world adult (≥18 years) CHB patient (ICD-10: B18.1) population from the Medical Data Vision database from January 01, 2012, to December 31, 2016. Comorbidities were identified by ICD-10 codes, and the annual point prevalence and Charlson Comorbidity Index (CCI) score were calculated. Annual mean and median all-cause healthcare utilization and costs per patient were calculated. Comparison tests were conducted for CCI scores, prevalence of comorbidities, and healthcare resource utilization and costs. Results: We identified 11,125 CHB patients. Between 2012 and 2016, the mean age increased from 62.0 to 65.2 years, and the percentage of those aged ≥65 years increased from 45.6% to 60.7%. The prevalence of cirrhosis remained similar (5.8% in 2012 and 5.6% in 2016, p = 0.69) while hepatocellular carcinoma decreased from 6.3% to 4.5% (p < 0.01). The prevalence of nonliver comorbidities increased (40.9–52.0% for cancer [p < 0.01], 12.1–17.7% for osteoporosis [p < 0.01], and 10.7–15.0% for renal impairment [p < 0.01]). Healthcare resource utilization and costs also increased, with a 119.3% increase in median total healthcare costs from JPY 229,143 in 2012 to 502,467 in 2016 (p < 0.01). Conclusions: The CHB population of Japan is predominantly elderly and carry a high nonliver comorbidity burden, while incurring increasing healthcare costs.