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Background Gastric and colorectal cancer (CRC) are both one of the most common cancers worldwide. In many countries fecal immunochemical tests (FIT)-based CRC screening has been implemented. We investigated if FIT can also be applied for detection of H. pylori, the main risk factor for gastric cancer. Methods This prospective study included participants over 18 years of age referred for urea breath test (UBT). Patients were excluded if they had used antibiotics/bismuth in the past 4 weeks, or a proton pomp inhibitor (PPI) in the past 2 weeks. Participants underwent UBT, ELISA stool antigen test in standard feces tube (SAT), ELISA stool antigen test in FIT tube (Hp-FIT), and blood sampling, and completed a questionnaire on user friendliness. UBT results were used as reference. Results A total of 182 patients were included (37.4% male, median age 52.4 years (IQR 22.4)). Of these, 60 (33.0%) tested H. pylori positive. SAT and Hp-FIT showed comparable overall accuracy 71.1% (95%CI 63.2–78.3) vs. 77.6% (95%CI 70.4–83.8), respectively (p = 0.97). Sensitivity of SAT was 91.8% (95%CI 80.4–97.7) versus 94.2% (95%CI 84.1–98.9) of Hp-FIT (p = 0.98). Serology scored low with an overall accuracy of 49.7% (95%CI 41.7–57.7). Hp-FIT showed the highest overall user convenience. Conclusions FIT can be used with high accuracy and sensitivity for diagnosis of H. pylori and is rated as the most convenient test. Non-invasive Hp-FIT test is highly promising for combined upper and lower gastrointestinal (pre-) cancerous screening. Further research should investigate the clinical implications, benefits and cost-effectiveness of such an approach.

ObjectivesThe treatment workload associated with end-stage kidney disease (ESKD) is high. The treatment burdens experienced by patients with ESKD are not well understood. In this study, we aimed to elucidate the most important areas of treatment burden for discussion in a clinical encounter from the perspectives of patients with ESKD and nephrologists. We sought to explore possible solutions to these high priority treatment burden challenges.DesignNominal group technique (NGT) sessions.Setting and participantsThree in-person NGT sessions were conducted with 19 patients with dialysis-dependent ESKD from one tertiary treatment centre (mean age 64 years; range 47–82). All patients were either retired or on a disability pension; 74% perceived moderate or severe treatment burden; and 90% spent more than 11 hours on treatment-related activities per week (range 11–30). One online NGT session was conducted with six nephrologists from two Australian states.Main outcome measuresThe primary outcome was a ranked list of treatment burden priorities. The secondary outcome was potential solutions to these treatment burden challenges.ResultsEvery patient group rankedhealth system issuesas the most important treatment burden priority. This encompassed lack of continuity and coordination of care, dissatisfaction with frequent healthcare encounters and challenges around healthcare access.Psychosocial burdenson patients and families were perceived to be the most important area of treatment burden by physicians, and were ranked the second highest priority by patients.ConclusionsDiscussing treatment burden in a clinical encounter may lead to a better understanding of patients’ capacity to cope with their treatment workload. This could facilitate tailored care, improve health outcomes, treatment sustainability and patients’ overall quality of life.

Despite most of the prolactinomas can be treated with endocrine therapy and/or surgery, a significant percentage of these tumors can be resistant to endocrine treatments and/or recur with prominent invasion into the surrounding anatomical structures. Hence, clinical, pathological, and molecular definitions of aggressive prolactinomas are important to guide for classical and novel treatment modalities. In this review, we aimed to define molecular endocrinological features of dopamine agonist-resistant and aggressive prolactinomas for designing future multimodality treatments. Besides surgery, temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide therapy, estrogen pathway modulators, progesterone antagonists or agonists, mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib, everolimus, and metformin are tested in preclinical models, anecdotal cases, and in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing hormone, TGFβ and PRDM2 may seem like possible future targets for managing aggressive prolactinomas. Lastly, we discussed our management of a unique prolactinoma case by asking which tumors’ proliferative index (Ki67) increased from 5–6% to 26% in two subsequent surgeries performed in a 2-year period, exerted massive invasive growth, and secreted huge levels of prolactin leading up to levels of 1 605 671 ng/dl in blood.

Purpose To present the different clinical manifestations of rhino-orbital mucormycosis (ROM) co-infection in severe COVID-19 patients. Study design Prospective observational clinical study Methods Among 32,814 patients hospitalized with the diagnosis of COVID-19 between March 2020 and December 2020 in our center, eleven microbiologically confirmed ROM co-infection cases in severe COVID-19 patients were evaluated. Results There were nine men and two women with a mean age of 73.1 ± 7.7 years. Eight patients had uncontrolled type 2 diabetes with a mean diagnosis duration of 12.1 ± 4.4 years. All patients had COVID-19-associated acute respiratory distress syndrome and received corticosteroids. The mean time interval between COVID-19 diagnosis and ROM diagnosis was 14.4 ± 4.3 days. Seven patients (63.6%) had orbital apex syndrome, and four patients (36.4%) presented with orbital cellulitis. Endophthalmitis was detected in 54.5% of patients, and two of these patients developed retinoschisis. CT scan/MRI revealed sino-orbital involvement in all patients, and three of these had cerebral involvement at initial presentation. All patients received intravenous and retrobulbar liposomal amphotericin B and had undergone radical debridement of involved sinuses. Intravitreal liposomal amphotericin B injected in patients with endophthalmitis. Despite all measures, 63.6% of patients expired. Conclusions Severe COVID-19 is associated with a significant incidence of ROM with higher mortality rates due to immune dysregulation and the widespread use of steroids. Physicians should be aware of the possibility of this infection in patients with COVID-19. An aggressive multidisciplinary approach can help to reduce mortality. Supplementary Information The online version contains supplementary material available at 10.1007/s10384-021-00845-5.

Background/aim: Hantavirus is a rodent borne zoonosis caused by the members of the virus family Bunyaviridae, genus Hantavirus. In this study, we aimed to determine the role of peripheral blood leukocyte ratio in differential diagnosis of Hantavirus disease. Materials and methods: The medical records of patients at the Duzce University Medical Faculty were examined retrospectively. A total of 20 patients diagnosed with hantavirus infection confirmed by serologic tests were included in the study (Group 1). The other group consisted of 30 patients suspected of hantavirus infection but found negative (Group 2). Demographic, clinical and laboratory characteristics, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte (LMR) ratios of both groups were compared. Results: As a result of the istatistics analysis, no difference was found between the groups' age, sex, and clinical complaints except lethargy-weakness (P = 0.004) and diarrhea (P < 0.001). Hemogram analysis showed a significant difference between the groups in terms of leukocyte, hemoglobin, hematocrit, platelet, mean platelet volume (P < 0.05) and PLR (P = 0.001) and LMR (P = 0.003) values from peripheral blood leukocyte ratios. Conclusion: In conclusion, NLR, PLR, and LMR ratios may be useful for clinicians in differential diagnosis of Hantavirus in patients presenting with similar symptoms of Hantavirus disease. WOS:000623196400035 2-s2.0-85102263620 PubMed: 33021756

Purpose: Transgender, including gender diverse and nonbinary (trans), people experience significant health disparities. We aimed to better understand the health status and needs of Australian trans people to guide resources and health and well-being programs. Methods: This anonymous, cross-sectional online survey utilized nonprobability snowball sampling of Australian adults (18 years and over) who self-identified as trans between September 2017 and January 2018. This descriptive study assessed demographic data, community views on access to health care, health burden, access to health resources, and priorities for government funding in transgender health. Results: Of 928 participants, 37% reported female, 36% reported male, and 27% reported nonbinary gender identities. Despite 47% having tertiary qualifications, the unemployment rate was 19%, with 33% reporting discrimination in employment due to being trans. Discrimination in accessing health care was reported by 26% and verbal abuse and physical assault were reported by 63% and 22%, respectively. Lifetime diagnosis of depression was reported by 73% and anxiety by 67%. Sixty-three percent reported previous self-harm and 43% had attempted suicide. Autism spectrum disorder and attention-deficit/hyperactivity disorder were reported by 15% and 11%, respectively. The most preferred method of receiving health information was through online resources, with the most popular source being Reddit, an online peer discussion board. Better training for doctors in trans health issues was the top priority for government funding. Conclusions: Barriers, including widespread discrimination and unemployment, contribute to health inequity and prevalent mental health conditions. Better training for health professionals in the provision of safe, gender-affirming and general health care for trans people is urgently required.

Background Despite numerous national and international efforts to alleviate child growth faltering, it remains a global health challenge. There is a growing body of literature that recognizes the importance of women’s empowerment in a wide range of public health topics, such as the utilization of maternal healthcare services, agricultural productivity, and child nutrition. However, in Ethiopia, the relationship between women’s empowerment and child nutritional status is not studied at the national level. This study aimed to determine the association between women’s empowerment and growth faltering in under-5 children in Ethiopia. Methods The data source for this analysis is the 2016 Ethiopian Demographic and Health Survey (EDHS): a nationally representative household survey on healthcare. The EDHS employed a two-stage stratified cluster sampling technique. We computed standard women’s empowerment indices, following the Survey-based Women’s emPowERment index approach. A multilevel logistic regression model that accounted for cluster-level random effects was used to estimate the association between women’s empowerment and child growth faltering (stunting, wasting and underweight). Results Attitude to violence, social independence, and decision-making were the three domains of women’s empowerment that were associated with child growth faltering. One standard deviation increase in each domain of empowerment was associated with a reduction in the odds of stunting: attitude towards violence (AOR = 0.92; 95% CI 0.88–0.96; p p = 0.049), and decision-making (AOR = 0.93; 95% CI 0.87–0.99; p = 0.023). Similarly, each standard deviation increase in attitude towards violence (AOR = 0.93; 95% CI 0.89–0.98; p = 0.008), social independence (AOR = 0.91; 95% CI 0.86–0.97; p = 0.002), and decision-making (AOR = 0.92; 95% CI 0.86–0.99; p = 0.020) were associated with a decrease in the odds of having underweight child. Conclusions Ensuring women’s empowerment both in the household and in the community could have the potential to decrease stunting and underweight in a rapidly developing country like Ethiopia. Policymakers and health professionals need to consider women’s empowerment in this unique context to improve nutritional outcomes for children and alleviate growth faltering.

The frequency of opportunistic fungal infections in critically ill patients whose intensive care unit stays are prolonged due to coronavirus disease 2019 (COVID-19) is higher than in the period before COVID-19. We planned this study to improve the management of

IntroductionGender affirming hormone therapy (GAHT) is increasingly used by transgender individuals and leads to shifts in sex hormone levels. Skeletal muscle is highly responsive to hormone activity, with limited data on the effects of GAHT on different human tissues. Here, we present the protocol for the GAME study (the effects ofGenderAffirming hormone therapy on skeletalMuscle training andEpigenetics), which aims to uncover the effects of GAHT on skeletal muscle ‘omic’ profiles (methylomics, transcriptomics, proteomics, metabolomics) and markers of skeletal muscle health and fitness.Methods and analysisThis study is a prospective age-matched cohort study in transgender adults commencing GAHT (n=80) and age-matched individuals not commencing GAHT (n=80), conducted at Austin Health and Victoria University in Victoria, Australia. Assessments will take place prior to beginning GAHT and 6 and 12 months into therapies in adults commencing GAHT. Age-matched individuals will be assessed at the same time points. Assessments will be divided over three examination days, involving (1) aerobic fitness tests, (2) muscle strength assessments and (3) collection of blood and muscle samples, as well as body composition measurements. Standardised diets, fitness watches and questionnaires will be used to control for key confounders in analyses. Primary outcomes are changes in aerobic fitness and muscle strength, as well as changes in skeletal muscle DNA methylation and gene expression profiles. Secondary outcomes include changes in skeletal muscle characteristics, proteomics, body composition and blood markers. Linear mixed models will be used to assess changes in outcomes, while accounting for repeated measures within participants and adjusting for known confounders.Ethics and disseminationThe Austin Health Human Research Ethics Committee (HREC) and Victoria University HREC granted approval for this study (HREC/77146/Austin-2021). Findings from this project will be published in open-access, peer-reviewed journals and presented to scientific and public audiences.Trial registration numberACTRN12621001415897; Pre-results.

Context As the number of transgender (trans) people (including those who are binary and/or nonbinary identified) seeking gender-affirming hormone therapy rises, endocrinologists are increasingly asked to assist with interpretation of laboratory tests. Many common laboratory tests such as hemoglobin, iron studies, cardiac troponin, and creatinine are affected by sex steroids or body size. We seek to provide a summary of the impact of feminizing and masculinizing hormone therapy on common laboratory tests and an approach to interpretation. Cases Case scenarios discussed include 1) hemoglobin and hematocrit in a nonbinary person undergoing masculinizing hormone therapy; 2) estimation of glomerular filtration rate in a trans woman at risk of contrast-induced nephropathy; 3) prostate-specific antigen (PSA) in a trans woman; and 4) chest pain in a trans man with a cardiac troponin concentration between the reported male and female reference ranges. Conclusions The influence of exogenous gender-affirming hormone therapy on fat and muscle distribution and other physiological changes determines interpretation of laboratory tests that have sex-specific differences. In addition to affirmative practice to ensure a patient’s name, gender, and pronoun are used appropriately, we propose that once individuals have commenced gender-affirming hormone therapy, the reference range of the affirmed gender be reported (and specified by treating clinicians) except for PSA or cardiac troponin, which are dependent on organ size. While suggestions may be challenging to implement, they also represent an opportunity to lead best practice to improve the quality of care and experiences of healthcare for all trans people.

Objective Type 1 diabetes (T1D) is a disease characterized by severe insulin deficiency. In 2008 our group studied the prevalence of diabetes in adults between 20-80 years of age in Cyprus but data regarding this incidence in the pediatric population is lacking. The objective of this study was to report the incidence of T1D among permanent inhabitants aged 16 years or younger between 2001-2016 in Cyprus. Methods This study was a retrospective analysis. The patients were mainly evaluated and recorded at Dr. Burhan Nalbantoglu Hospital, Nicosia. Data was also reviewed from Famagusta Government Hospital, Kyrenia Government Hospital, Near East University Hospital and the Cyprus Turkish Diabetes Association. Results A total of 107 subjects were diagnosed as T1D between 2001 and 2016 in the pediatric age group. Forty-nine (45.7%) were girls and 58 (54.3%) were boys. Of these 38.7% were resident in Nicosia, 30.2% Famagusta, 12.3% Kyrenia, 9.4% Guzelyurt and 7.5% Iskele. The proportion of newly diagnosed T1D was highest among children aged 9-12 years (35.5%) followed by children aged 5-8 years (32.7%). Newly diagnosed T1D most frequently presented in March and April. The overall mean incidence rate was 11.1/100,000 between 2001 and 2016. The incidence rates were similar and comparable among the years. Conclusion This study is the first to analyze the incidence of T1D in Cyprus. Compared to other countries the incidence rate is intermediate. Our findings are similar to the incidence rates of T1D in South Cyprus and Turkey.

Many of the considerable number of young people who identify as transgender or gender diverse do not conform to traditional binary notions of gender (male vs female), and instead have a non-binary gender identity. This narrative Review summarises literature related to the sociodemographic and clinical profiles of young people with a non-binary gender identity. Young people identifying as non-binary form a substantial minority of the general population. They experience lower levels of support and are at increased risk of experiencing abuse and victimisation than young people who are cisgender. Furthermore, compared with young people who are transgender and binary, people who identify as non-binary experience less access to trans-specific health care. Young people identifying as non-binary have poor mental health outcomes, with high rates of depression, anxiety, and suicidal ideation that were found to be similar if not higher than in those who are transgender and binary. This Review highlights that young people who identify as non-binary are highly vulnerable and likely to have important health-care needs.

The aim of this study was to summarize strategies to reduce postsurgical opioid prescribing at discharge.Current practices for the prescription of opioids at discharge after surgery are highly variable and often excessive. We conducted a systematic review to identify behavioral interventions designed to improve these practices.We searched MEDLINE, EMBASE, CINAHL, and PsycINFO until December 14, 2018 to identify studies of behavioral interventions designed to decrease opioid prescribing at discharge among adults undergoing surgery. Behavioral interventions were defined according to the Cochrane Effective Practice and Organisation of Care (EPOC) taxonomy. We assessed the risk of bias of included studies using criteria suggested by Cochrane EPOC and the Newcastle-Ottawa scale.Of 8048 citations that were screened, 24 studies were included in our review. Six types of behavioral interventions were identified: local consensus-based processes (18 studies), patient-mediated interventions (2 studies), clinical practice guidelines (1 study), educational meetings (1 study), interprofessional education (1 study), and clinician reminder (1 study). All but one study reported a statistically significant decrease in the amount of opioid prescribed at discharge after surgery, and only 2 studies reported evidence of increased pain intensity. Reductions in prescribed opioids ranged from 34.4 to 212.3 mg morphine equivalents. All studies were found to have medium-to-high risks of bias.We identified 6 types of behavioral strategies to decrease opioid prescription at discharge after surgery. Despite the risk of bias, almost all types of intervention seemed effective in reducing opioid prescriptions at discharge after surgery without negatively impacting pain control.

Adem Sav,1 Sarah T Thomas,2 Magnolia Cardona,3,4 Zoe A Michaleff,4,5 Claudia C Dobler3,4,6 1School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia; 2Gold Coast University Hospital, Southport, Queensland, Australia; 3Evidence-Based Practice Professorial Unit, Gold Coast Hospital, Southport, Queensland, Australia; 4Institute for Evidence Based Healthcare, Bond University, Gold Coast, Queensland, Australia; 5Northern NSW Local Health District, Lismore, New South Wales, Australia; 6The George Institute for Global Health, University of New South Wales, Kensington, New South Wales, AustraliaCorrespondence: Adem Sav, School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia, Tel +61 7 3138 5795, Email adem.sav@qut.edu.auPurpose: Many people with chronic obstructive pulmonary disease (COPD) feel overburdened with the treatment and management of their illness. Although research has begun to shed light on how COPD patients experience treatment burden, most of what we know is limited to personal experiences of patients. The aim of this study is to identify and prioritise areas of treatment burden that should be discussed during the clinical encounter from the perspectives of COPD patients, carers, and respiratory physicians.Patients and Methods: Data were collected from participants using the nominal group technique. Five nominal group sessions were conducted in total (n = 31); three sessions with patients (n = 18), one with carers (n = 7) and another with respiratory physicians (pulmonologists or chest physicians) (n = 6). Each session was recorded and analyzed using thematic analysis.Results: Going beyond understanding patients’ and carers’ experiences of treatment burden, this study offers a practical viewpoint of what should be discussed in a clinical encounter. Each group of participants contextualized treatment burden issues for discussion from their own perspectives. There was strong agreement, however, across the groups that difficulties accessing healthcare, lack of education and information, and worry about COPD treatment and prognosis were the most important treatment burden priorities for discussion.Conclusion: Understanding and creating opportunities to discuss these issues in a clinical encounter is important in not only reducing treatment burden but also improving health outcomes and quality of life for COPD patients and their carers.Keywords: COPD, burden of treatment, treatment burden, nominal group technique

Hypophysitis is defined as inflammation of the pituitary gland that is primary or secondary to a local or systemic process. Differential diagnosis is broad (including primary tumors, metastases, and lympho-proliferative diseases) and multifaceted. Patients with hypophysitis typically present with headaches, some degree of anterior and/or posterior pituitary dysfunction, and enlargement of pituitary gland and/or stalk, as determined by imaging. Most hypophysitis causes are autoimmune, but other etiologies include inflammation secondary to sellar tumors or cysts, systemic diseases, and infection or drug-induced causes. Novel pathologies such as immunoglobulin G4-related hypophysitis, immunotherapy-induced hypophysitis, and paraneoplastic pituitary-directed autoimmunity are also included in a growing spectrum of this rare pituitary disease. Typical magnetic resonance imaging reveals stalk thickening and homogenous enlargement of the pituitary gland; however, imaging is not always specific. Diagnosis can be challenging, and ultimately, only a pituitary biopsy can confirm hypophysitis type and rule out other etiologies. A presumptive diagnosis can be made often without biopsy. Detailed history and clinical examination are essential, notably for signs of underlying etiology with systemic manifestations. Hormone replacement and, in selected cases, careful observation is advised with imaging follow-up. High-dose glucocorticoids are initiated mainly to help reduce mass effect. A response may be observed in all auto-immune etiologies, as well as in lymphoproliferative diseases, and, as such, should not be used for differential diagnosis. Surgery may be necessary in some cases to relieve mass effect and allow a definite diagnosis. Immunosuppressive therapy and radiation are sometimes also necessary in resistant cases.

Transgender, including gender diverse and non-binary people, henceforth referred to collectively as trans people, are a highly marginalised population with alarming rates of suicidal ideation, attempted suicide and self-harm. We aimed to understand the risk and protective factors of a lifetime history of attempted suicide in a community sample of Australian trans adults to guide better mental health support and suicide prevention strategies.Using a non-probability snowball sampling approach, a total of 928 trans adults completed a cross-sectional online survey between September 2017 and January 2018. The survey assessed demographic data, mental health morbidity, a lifetime history of intentional self-harm and attempted suicide, experiences of discrimination, experiences of assault, access to gender affirming healthcare and access to trans peer support groups. Logistic regression was used to examine the risk or protective effect of participant characteristics on the odds of suicide.Of 928 participants, 85% self-reported a lifetime diagnosis of depression, 63% reported previous self-harm, and 43% had attempted suicide. Higher odds of reporting a lifetime history of suicide attempts were found in people who were; unemployed (adjusted odds ratio (aOR) 1.55 (1.05, 2.29), p = 0.03), had a diagnosis of depression (aOR 3.70 (2.51, 5.45), p 0.001), desired gender affirming surgery in the future (aOR 1.73 (1.14, 2.61), p = 0.01), had experienced physical assault (aOR 2.01 (1.37, 2.95), p 0.001) or experienced institutional discrimination related to their trans status (aOR 1.59 (1.14, 2.23), p = 0.007).Suicidality is associated with barriers to gender affirming care, gender based victimisation and institutionalised cissexism. Interventions to increase social inclusion, reduce transphobia and enable timely access to gender affirming care, particularly surgical interventions, are potential areas of intervention.

To systematically review and synthesize the published literature regarding the education of general practitioners (GPs) and GPs in training (GPTs) in the use of ultrasonography.This systematic review was prospectively registered in PROSPERO, conducted according to the Cochrane recommendations. We combined studies identified in a previous systematic review with studies from an updated literature search using the same search string. We searched the following databases: MEDLINE via Pubmed, EMBASE via OVID, Cinahl via Ebsco, Web of Science and Cochrane Register of Controlled Trials using the words 'ultrasonography' and 'general practice'. Two reviewers independently screened articles, extracted data and assessed the quality of included papers according to the Down and Black quality assessment tool. Disagreements were resolved by involving a third reviewer.Thirty-three papers were included. Ultrasound training was described to include both theoretical and practical training sessions. Theoretical training was achieved through introductory e-learning and/or didactic lectures. Practical training included focussed hands-on training sessions, while some papers described additional longitudinal practical training through proctored scans during clinical work or through self-study practice with continuous feedback on recorded scans.There was a large variation in ultrasound training programs for GPs and GPTs, with an overall emphasis on focussed practical training. Few studies included a longitudinal learning process in the training program. However, diagnostic accuracy seemed to improve with hours of practical training, and studies including continuous feedback on scans conducted during clinical patient encounters showed superior results.Point-of-care ultrasonography is increasingly used by general practitioners (GPs) working in primary care as a diagnostic tool providing earlier and more precise diagnoses. However, ultrasonography is a user-dependent technology and obtaining competence requires both training and practice. Today, there is no consensus about which ultrasound training GPs should have before they start scanning patients in their clinics.

Background Meningiomas are heterogeneous, with differences in anatomical, histopathological, and clinical characteristics. Such spatial variability in meningioma biology is thought to result from differences in the expression of critical developmental regulators. We hypothesized that the variability in meningioma biology would follow gradients such as in embryology and tested a cohort of 366 meningiomas for histopathological and immunohistochemical gradients. Methods The medical records from 366 patients treated for meningiomas from 2003 to 2016 were retrospectively analyzed for age, gender, anatomical localization, recurrence-free survival, overall survival, histopathological diagnosis, and immunohistochemistry findings for 6 markers: epithelial membrane antigen (EMA), progesterone receptor (PR), CD34, S100, p53, and Ki-67 labeling index. Results EMA, PR, S100, p53, and CD34 were expressed in 94%, 73%, 49%, 26%, and 23% of the tumors, respectively. p53 expression correlated positively with Ki-67 and World Health Organization (WHO) grade (rτ = 0.31 and rτ = 0.4, respectively). PR positivity correlated inversely with S100, p53, Ki-67, and WHO grade (rτ = −0.19, rτ = −0.14, rτ = −0.15, and rτ = −0.16, respectively). All secretory meningiomas were positive for EMA and PR and negative for S100, and this pattern exhibited a rostrocaudal gradient. The overall proportion of EMA+PR+S100− cases was significantly lower in the cranial vault (30.3%) than in the skull base (45.89%; P = 0.021). The proportion of WHO grade II-III tumors was greater in cranial vault than in skull base meningiomas. Conclusions Unsupervised methods detected an association between the anatomical location and tumor biology in meningiomas. Unlike the categorical associations that former studies had indicated, the present study revealed a rostrocaudal gradient in both the cranial vault and the skull base, correlating with human developmental biology.

Purpose: Pterygium, one of the most common ocular surface diseases, is characterized by inflammatory infiltrates, proliferation, angiogenesis, fibrosis, and extracellular matrix breakdown. The obje...

Gender dysphoria describes the distress associated with having a gender identity that differs from one’s birth-assigned sex. To relieve this distress, transgender, and gender diverse (henceforth, trans) individuals commonly undergo medical transition involving hormonal treatments. Current hormonal treatment guidelines cater almost exclusively for those who wish to transition from male to female or vice versa. In contrast, there is a dearth of hormonal options for those trans individuals who identify as non-binary and seek an androgynous appearance that is neither overtly male nor female. Though prolonged puberty suppression with gonadotrophin releasing hormone agonists (GnRHa) could in theory be gender-affirming by preventing the development of unwanted secondary sex characteristics, this treatment option would be limited to pre- or peri-pubertal adolescents and likely have harmful effects. Here, we discuss the theoretical use of Selective Estrogen Receptor Modulators (SERMs) for non-binary people assigned male at birth (AMAB) who are seeking an androgynous appearance through partial feminization without breast growth. Given their unique range of pharmacodynamic effects, SERMs may represent a potential gender-affirming treatment for this population, but there is a lack of knowledge regarding their use and potentially adverse effects in this context.

Blocking tumor vascularization has not yet come to fruition to the extent it was hoped for, as angiogenesis inhibitors have shown only partial success in the clinic. We hypothesized that under-appreciated vascular wall-resident stem and progenitor cells (VW-SPCs) might be involved in tumor vascularization and influence effectiveness of anti-angiogenic therapy. Indeed, in patient samples, we observed that vascular adventitia-resident CD34+ VW-SPCs are recruited to tumors in situ from co-opted vessels. To elucidate this in detail, we established an ex vivo model using concomitant embedding of multi-cellular tumor spheroids (MCTS) and mouse aortic rings (ARs) into collagen gels, similar to the so-called aortic ring assay (ARA). Moreover, ARA was modified by removing the ARs’ adventitia that harbors VW-SPCs. Thus, this model enabled distinguishing the contribution of VW-SPCs from that of mature endothelial cells (ECs) to new vessel formation. Our results show that the formation of capillary-like sprouts is considerably delayed, and their number and network formation were significantly reduced by removing the adventitia. Substituting iPSC-derived neural spheroids for MCTS resulted in distinct sprouting patterns that were also strongly influenced by the presence or absence of VW-SPCs, also underlying the involvement of these cells in non-pathological vascularization. Our data suggest that more comprehensive approaches are needed in order to block all of the mechanisms contributing to tumor vascularization.

Background: Intramedullary glial neoplasms affecting the entire spinal cord from the cervicomedullary junction to conus medullaris are termed holocord tumors. Pilocytic astrocytomas are relatively uncommon tumors forming holocord involvement. Hitherto 24 holocord astrocytoma cases were reported in the literature. Here, a case of an adult holocord pilocytic astrocytoma was presented. Case Description: A 29-year-old female patient presented with a subtotal resection. Histopathologic examination revealed pilocytic astrocytoma, World Health Organization grade 1, presenting holocord involvement. Magnetic resonance imaging showed a mass containing necrotic and cystic foci leading to an expansion along the entire spinal cord extending from C4 to conus medullaris. Conclusions: Reported holocord pilocytic astrocytomas in the relevant literature cases were reviewed. When evaluating magnetic resonance imaging scans of adult patients with various neurologic symptoms, i.e., weakness and fecal and urinary incontinence, pilocytic astrocytoma should be considered among differential diagnoses of intramedullary mass lesions. © 2019 Elsevier Inc.

Emerging adulthood is a transitional life stage with increased probability of risky and unhealthy lifestyle behaviours that are known to have strong links with premature mortality and morbidity. Wellbeing, as a positive subjective experience, is identified as a factor that encourages self-care and may steer individuals away from risky lifestyle behaviours. Investigating wellbeing&ndash, behaviour links in the emerging adult population may increase understanding of the factors that lead to, and ways to prevent, engagement in risky behaviours. This study examines the association between flourishing, that is, the experience of both high hedonic and eudaimonic wellbeing, and a broad range of risky and unhealthy lifestyle behaviours among emerging adults in Australia. A cross-sectional survey of 1155 emerging adults aged 18&ndash, 25 years measured wellbeing, socio-demographics, and six groups of lifestyle behaviours surrounding substance use, physical activity, diet, sex, sun protection, and driving. Bivariate and multivariate statistics were used to analyse the data. The findings revealed that flourishing was negatively associated with more dangerous types of risk behaviours, such as driving under the influence of drugs, and positively associated with self-care behaviours, such as healthier dietary behaviour and sun protection. If enabling emerging adults to flourish can contribute to reduced engagement in risky/unhealthy lifestyle behaviours, then promoting it is an important goal for health promotion efforts not only because flourishing is desirable in its own right, but also to bring about sustainable change in behaviour. Further research is needed to inform the designs of such interventions.

Oral candidiasis is a common fungal infection, affecting the oral mucosa. The aim of this study was to investigate the epidemiology and antifungal susceptibility of Candida species isolated from the oral cavity of patients affected by oral candidiasis. Oral swabs were taken from 34 patients and were inoculated on to Sabouraud Dextrose Agar (SDA). The yeasts were preliminarily evaluated according to the growth (human serum) germ tube, chlamydospore formation, reproduction at 45 degrees C and colony characteristics on SDA medium. The commercial method Phoenix (Becton Dickinson, USA) was used for identification. Clinical and Laboratory Standards Institute (CLSI) reference M27-A3 microdilution method was applied for fluconazole (FLC), voriconazole (VRC), amphotericin B (AMB), ketoconazole (KTC), nystatin (NYT) antifungal susceptibility testing. A total of 34 Candida species were isolated and these species were identified as follows: 14 (41.2%) Candida albicans, 8 (23.5%) Candida glabrata, 8 (23.5%) Candida parapsilosis, 4 (11.8 %) Candida tropicalis. The geometric mean (GM) of the Minimum Inhibitory Concentration (MIC) for FLC, NYT, VRC, AMB, and KTC was 13.09 μg/mL, 4.77 μg/mL, 0.23 μg/mL, 0.20 μg/mL, 0.08 μg/mL, respectively. The most commonly isolated species was C. albicans. KTZ showed the lowest MIC value. NYT MIC values for non-albicans species were higher than for C. albicans ones.

Introduction: Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK. Methods: Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA. Results: The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively). Conclusions: MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria. Resumo Introdução: A hiperfiltração glomerular pode causar proteinúria e doença renal crônica no rim displásico multicístico unilateral (RDM). Nosso objetivo foi investigar os níveis de lipocalina associada à gelatinase neutrofílica na urina (NGAL), netrina-1, hepcidina e quimiocina C-C com ligante-2 (MCP-1/CCL-2) em pacientes com RDM. Métodos: Trinta e dois pacientes e 25 controles foram incluídos. Os níveis urinários de hepcidina, netrin-1, NGAL e MCP-1/CCL-2 foram determinados por ELISA. Resultados: Os pacientes apresentaram níveis séricos mais elevados de creatinina (Cr), albumina na urina e relação netrina-1/Cr com menor TFG. Houve correlação positiva entre proteína na urina/Cr, MCP-1/CCL-2/Cr e netrina-1 com NGAL (r = 0,397, p = 0,031; r = 0,437, p = 0,041, r = 0,323, p = 0,042, respectivamente). A netrina-1/Cr na urina foi correlacionada positivamente com MCP-1/CCL-2/Cr (r = 0,356, p = 0,045). Houve associações positivas entre a presença de proteinúria e netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr [Odds ratio (OR): 1,423, p = 0,037, OR: 1,553, p = 0,033, OR: 2,112, p = 0,027, respectivamente) ]. A análise da curva ROC mostrou que netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr apresentaram altos valores preditivos para determinar a proteinúria p = 0,027, p = 0,041, p = 0,035, respectivamente). A hepcidina/Cr na urina foi correlacionada negativamente com a reabsorção tubular de fósforo e positivamente com a NGAL/Cr na urina (r = -0,418, p = 0,019; r = 0,682, p = 0,000; respectivamente). Conclusões: MCP-1/CCL-2 pode ter participação no desenvolvimento de proteinúria no RDM. A Netrina-1 pode ser um fator protetor contra lesão renal induzida por proteinúria. Hepcidina/Cr na urina pode refletir danos em túbulos proximais no RDM. O valor de NGAL/Cr urinário pode ser um preditor de danos nos túbulos por proteinúria.

Context The relationship between the endocrine system and autoimmunity has been recognized for a long time and one of the best examples of autoimmune endocrine disease is autoimmune hypophysitis. A better understanding of autoimmune mechanisms and radiological, biochemical, and immunological developments has given rise to the definition of new autoimmune disorders including autoimmunity-related hypothalamic–pituitary disorders. However, whether hypothalamitis may occur as a distinct entity is still a matter of debate. Evidence Acquisition Here we describe a 35-year-old woman with growing suprasellar mass, partial empty sella, central diabetes insipidus, hypopituitarism, and hyperprolactinemia. Evidence Synthesis Histopathologic examination of surgically removed suprasellar mass revealed lymphocytic infiltrate suggestive of an autoimmune disease with hypothalamic involvement. The presence of antihypothalamus antibodies to arginine vasopressin (AVP)-secreting cells (AVPcAb) at high titers and the absence of antipituitary antibodies suggested the diagnosis of isolated hypothalamitis. Some similar conditions have sometimes been reported in the literature but the simultaneous double finding of lymphocytic infiltrate and the presence of AVPcAb so far has never been reported. Conclusions We think that the hypothalamitis can be considered a new isolated autoimmune disease affecting the hypothalamus while the lymphocytic infundibuloneurohypophysitis can be a consequence of hypothalamitis with subsequent autoimmune involvement of the pituitary. To our knowledge this is the first observation of autoimmune hypothalamic involvement with central diabetes insipidus, partial empty sella, antihypothalamic antibodies and hypopituitarism.

Mutations in isocitrate dehydrogenase genes IDH1 and IDH2 are frequently found in diffuse and anaplastic astrocytic and oligodendroglial tumours as well as in secondary glioblastomas. As IDH is a very important prognostic, diagnostic and therapeutic biomarker for glioma, it is of paramount importance to determine its mutational status. The haematoxylin and eosin (H&E) staining is a valuable tool in precision oncology as it guides histopathology-based diagnosis and proceeding patient’s treatment. However, H&E staining alone does not determine the IDH mutational status of a tumour. Deep learning methods applied to MRI data have been demonstrated to be a useful tool in IDH status prediction, however the effectiveness of deep learning on H&E slides in the clinical setting has not been investigated so far. Furthermore, the performance of deep learning methods in medical imaging has been practically limited by small sample sizes currently available. Here we propose a data augmentation method based on the Generative Adversarial Networks (GAN) deep learning methodology, to improve the prediction performance of IDH mutational status using H&E slides. The H&E slides were acquired from 266 grade II-IV glioma patients from a mixture of public and private databases, including 130 IDH-wildtype and 136 IDH-mutant patients. A baseline deep learning model without data augmentation achieved an accuracy of 0.794 (AUC = 0.920). With GAN-based data augmentation, the accuracy of the IDH mutational status prediction was improved to 0.853 (AUC = 0.927) when the 3,000 GAN generated training samples were added to the original training set (24,000 samples). By integrating also patients’ age into the model, the accuracy improved further to 0.882 (AUC = 0.931). Our findings show that deep learning methodology, enhanced by GAN data augmentation, can support physicians in gliomas’ IDH status prediction.

Overprescribing of opioids to patients following surgery is a public health concern, as unused pills may be diverted and contribute to opioid misuse and dependence. The objectives of this study were to determine current opioid-prescribing patterns for common surgical procedures, factors that affect surgeons’ prescribing behaviour and their perceived ability to manage patients with opioid use disorder.Survey participants included all consultant and trainee surgeons at the University of Toronto. The survey, which was administered electronically, included 52 multiple-choice, rank-order and open-text questions eliciting information on current prescribing patterns, prescribing of adjunct pain medications, and education and other factors related to opioid prescribing. Staff surgeons were also asked about how they manage patients with a suspected opioid issue.Eighty surgical trainees and 40 staff surgeons responded to the survey (response rate 32%). Five staff surgeons (12%) felt adequately educated to prescribe pain medications (including opioids) at discharge. Staff surgeons prescribed Tylenol 3 more frequently than other opioids. Twenty (51%) of 39 staff surgeons reported that they sought further help for their patients when an opioid use disorder was suspected.Our results support existing studies showing a large degree of variability in postoperative opioid prescribing. Institutional guidelines have been shown to be effective in curbing excessive opioid prescribing without increasing unnecessary emergency department visits for uncontrolled pain. Thus, there is an opportunity to develop institutional guidelines to educate surgical teams in the prescribing of opioids and about services available for patients with a substance use disorder.La surprescription d’opioïdes aux patients après une chirurgie représente un problème de santé publique car il y a un risque que les comprimés inutilisés soient détournés et utilisés à mauvais escient, voire qu’ils causent la dépendance. Cette étude avait pour objectif d’identifier les modes actuels de prescription des opioïdes pour les chirurgies courantes, les facteurs qui influent sur les habitudes de prescription des chirurgiens et leur capacité perçue à prendre en charge les cas de mésusage des opioïdes.Les participants au sondage étaient tous les chirurgiens en poste et en formation à l’Université de Toronto. Ce sondage administré par voie électronique comprenait 52 questions (choix multiples, échelles ordinales et ouvertes) qui visaient à recueillir des renseignements sur les modes actuels de prescription, la prescription d’analgésiques d’appoint, l’enseignement au patient et autres éléments relatifs à la prescription des opioïdes. Les chirurgiens en poste ont aussi été interrogés sur leur gestion des cas présumés de mésusage des opioïdes.Quatre-vingt chirurgiens en formation et 40 chirurgiens en poste ont répondu au sondage (taux de réponse, 32 %). Cinq chirurgiens en poste (12 %) se sont estimés adéquatement renseignés sur la façon de prescrire les analgésiques, (y compris les opioïdes) au moment du congé. Les chirurgiens en poste prescrivaient Tylenol 3 fois plus souvent que d’autres opioïdes. Vingt (51 %) chirurgiens en poste sur 39 ont dit consulter s’ils avaient besoin d’aide pour la prise en charge de patients soupçonnés de présenter un problème de mésusage des opioïdes.Nos résultats viennent étayer les conclusions d’études existantes selon lesquelles les modes de prescription des opioïdes en postopératoire varient grandement. Il a été démontré que l’adoption de lignes directrices institutionnelles permet de limiter efficacement la surprescription des opioïdes sans accroître indument le nombre de consultations aux urgences pour douleur non maîtrisée. Il y a donc là une possibilité d’adopter à plus grande échelle les lignes directrices institutionnelles pour sensibiliser les équipes chirurgicales à l’utilisation judicieuse des opioïdes et à l’existence des services à l’intention des patients qui présentent un problème de mésusage.

BackgroundCongenital malformations are structural, functional, and metabolic defects that develop during the organogenesis period and present at birth or later in life. There has been little research on congenital malformations in Ethiopia, knowledge on the incidence of birth defects at birth is unknown and the etiologies of the anomalies are limited. This study, therefore, aimed to assess the modifiable risks of congenital anomalies among women in Bale zone hospitals, Ethiopia.MethodsAn unmatched case-control study was conducted from February 2018 to January 2019 in the Bale zone; namely Goba referral hospital, Robe, Ginnir and Dolomena hospitals. A total of 409 women were selected. Mothers who gave birth with any type of congenital malformation were assigned as cases and those who gave live births without any congenital abnormalities were assigned as controls. Controls were selected by the lottery method from the labor ward. For each case, two consecutive controls were included. Data were entered into Epi-data 3.1 and exported into Statistical Package for the Social Sciences (SPSS) version 21 for analysis. Logistic regression was conducted to analyze the data.ResultsAlarmingly, women who had been exposed to pesticides during the current pregnancy were two times more prone to give congenital malformed infants than their counterparts (AOR = 3.19; 95% CI = 1.31, 10.96). Additionally, those women who chewedkhatduring the periconceptional period were two times more likely to have congenital malformed infants as compared to women who did not engage in this activity (AOR = 2.40; 95% CI = 1.11, 5.19).ConclusionsUrgent attention needs to be given by public health professionals and services tokhatchewing and maternal exposure to pesticides during pregnancy to reduce the risk of congenital malformations.

Traumatic brain injury most commonly affects young adults under the age of 35 and frequently results in reduced quality of life, disability, and death. In long-term survivors, hypopituitarism is a common complication. Pituitary dysfunction occurs in approximately 20–40% of patients diagnosed with moderate and severe traumatic brain injury giving rise to growth hormone deficiency, hypogonadism, hypothyroidism, hypocortisolism, and central diabetes insipidus. Varying degrees of hypopituitarism have been identified in patients during both the acute and chronic phase. Anterior pituitary hormone deficiency has been shown to cause morbidity and increase mortality in TBI patients, already encumbered by other complications. Hypopituitarism after childhood traumatic brain injury may cause treatable morbidity in those survivors. Prospective studies indicate that the incidence rate of hypopituitarism may be ten-fold higher than assumed; factors altering reports include case definition, geographic location, variable hospital coding, and lost notes. While the precise pathophysiology of post traumatic hypopituitarism has not yet been elucidated, it has been hypothesized that, apart from the primary mechanical event, secondary insults such as hypotension, hypoxia, increased intracranial pressure, as well as changes in cerebral flow and metabolism may contribute to hypothalamic-pituitary damage. A number of mechanisms have been proposed to clarify the causes of primary mechanical events giving rise to ischemic adenohypophysial infarction and the ensuing development of hypopituitarism. Future research should focus more on experimental and clinical studies to elucidate the exact mechanisms behind post-traumatic pituitary damage. The use of preventive medical measures to limit possible damage in the pituitary gland and hypothalamic pituitary axis in order to maintain or re-establish near normal physiologic functions are crucial to minimize the effects of TBI.

Many trans and gender diverse (TGD) people have gender identities that are not exclusively male or female but instead fall in-between or outside of the gender binary (non-binary). It remains unclear if and how those with non-binary gender identity differ from TGD individuals with binary identities. We aimed to understand the sociodemographic and mental health characteristics of people with non-binary identities compared with binary TGD identities. We performed a retrospective audit of new consultations for gender dysphoria between 2011 and 2016 in three clinical settings in Melbourne, Australia; (1) Equinox Clinic, an adult primary care clinic, (2) an adult endocrine specialist clinic, and (3) the Royal Children's Hospital, a child and adolescent specialist referral clinic. Age (grouped by decade), gender identity, sociodemographic, and mental health conditions were recorded. Of 895 TGD individuals, 128 (14.3%) had a non-binary gender. Proportions differed by clinical setting; 30.4% of people attending the adult primary care clinic, 7.4% attending the adult endocrine specialist clinic, and 8.0% attending the pediatric clinic identified as non-binary. A total of 29% of people in the 21-30-year-old age-group had a non-binary gender identity, higher than all other age-groups. Compared to TGD people with a binary gender identity, non-binary people had lower rates of gender-affirming interventions, and a higher prevalence of depression, anxiety, and illicit drug use. Tailoring clinical services to be inclusive of non-binary people and strategies to support mental health are required. Further research to better understand health needs and guide evidence-based gender-affirming interventions for non-binary people are needed.

New digital media platforms (e.g. social networking sites, web pages and text messaging) have dramatically changed interpersonal communication and present novel opportunities for health interventions. Due to the high uptake and use of digital media among young people, advances in digital media provide potential new opportunities in delivering health interventions to this audience to reduce sexually transmissible infection (STI) risk. The aim of this study was to assess the effectiveness of sexual health interventions delivered via new digital media to young people (aged 13–24 years). A systematic search was conducted of seven databases for peer-reviewed literature published between January 2010 and April 2017 that evaluated a sexual health intervention delivered to young people (aged 13–24 years). Of 2017 papers reviewed, 25 met the inclusion criteria and were assessed. Sixteen studies used web-based platforms to deliver their intervention. A large proportion of studies (11/25) specifically focused on HIV prevention. Seven studies found a statistically significant effect of the intervention on knowledge levels regarding the prevention HIV and other STI, as well as general sexual health knowledge, but only one-fifth of interventions evaluating intentions to use condoms reported significant effects due to the intervention. Nine studies focused on individuals from an African American background. Although new media has the capacity to expand efficiencies and coverage, the technology itself does not guarantee success. It is essential that interventions using new digital media have high-quality, evidence-based content that engages with individual participants.

Background: Social networks are known to have a major influence on the recovery journey of people with severe mental illness (SMI). Aims: To understand the role of bonding and bridging social capital in the recovery process following SMI and to identify the barriers that prevent social networks from being mobilized. Method: A review of major electronic databases for qualitative studies from 2006 to 2015 (41 papers) was undertaken for thematic synthesis. Result: The main themes for bonding social capital included: a buffer for isolation and loneliness, variations depending on illness stages, balance in relationships and connections as a source of self-management. Main themes for bridging social capital comprised: feeling powerless and excluded from community/health care, social care beyond the illness, social care barriers and social inclusion through community groups. Conclusion: All those involved in the management of SMI must be aware of how social support networks hinder or contribute to recovery. People with SMI need opportunities to form reciprocal relationships and sustain supportive networks that can assist them to endure the challenges presented by SMI.

Background Dural thickening is observed in lymphoma, dural carcinomatosis, meningioma, tuberculosis, and autoimmune diseases. We encountered a patient with dural thickening and complaints of neck and back pain, numbness and loss of strength in the hands. The patient also suffered from polychondritis and had previously received steroid and methotrexate treatment for this indication. The patients’ serum was also positive for ANA, yet she did not have any other findings suggesting lupus. Our radiological and pathological analysis revealed IHSP (IgG4-related hypertrophic sclerosing pachymeningitis). In this review study, we provided a detailed literature survey to increase the awareness about IHSP in the neurosurgical community. Methods MRI (magnetic resonance imaging)-based radiological analyses revealed a posterior extramedullary spinal mass extending from C2 to T2-T3 level. The dural mass was surgically excised and a broad panel of immunohistochemical markers including S100, EMA, CD246/ALK-1, CD45, CD20, CD79a, CD138, CD68, CD1a and CD34 was studied. Immunoglobulin heavy chain/kappa chain gene rearrangement analysis was performed which ruled out a lymphoproliferative disorder. Results MRI and pathological findings suggested IHSP. As the disease relapsed with a new anterior extramedullary multilobulated lesion extending from C5 to T1 level, the patient is now closely monitored for further medical and surgical treatment. Conclusions IHSP is a relatively novel entity of hypertrophic pachymeningitis and should be included in the differential diagnosis of dural thickening. The fibrosis accompanying IHSP may not respond to medical treatment, which includes steroids and immunosuppressive agents. Additionally, neurological deficits, seizures, spinal decompression, hydrocephalus, or brainstem compression necessitate early surgical intervention. A continued vigilance is also necessary as the disease may relapse long-term following surgical treatment.

Invasive fungal infections are a leading cause of morbidity and mortality in immunocompromised patients, especially in cases requiring a prolonged stay in the intensive care unit. A total of 99 yeast strains were isolated from 42 postmortem cases. In this study, virulence factors and antifungal susceptibility of these species were evaluated. The isolates were identified as Candida albicans (54), C. tropicalis (15), C. glabrata (12), C. parapsilosis (6), C. lipolytica (3), C. utilis (3), C. krusei (2), C. kefyr (1), and Cryptococcus neoformans (3). The most commonly isolated species was C. albicans, and no resistant species were determined. Despite the equal number of specimens, no secretion of significant virulence factors was associated with the postmortem specimen in the Candida species. Postmortem fungal investigations in forensic autopsies are useful in explaining cause of death in such cases, also may lead to protocols for the treatment of fungal infections and contribute to fungal pathogenesis and epidemiological data.

In systemic cancers, increased hemolysis leads to extracellular hemoglobin (HB), and experimental studies have shown its provoking role on tumor growth and metastasis. However, investigations have shown that HB chains presented by tumor vascular pericytes or serum protein complexes of HB could also induce antitumor immunity, which may be harnessed to treat refractory cancers and brain tumors. Mounting recent evidence shows that expression of HBs is not restricted to erythrocytes and that HBs exist in the cells of lung and kidney, in macrophages, and in neurons and glia of the central nervous system (CNS). HBs mediate coping with hypoxia and free radical stress in normal and tumor cells, and they are increased in certain tumors including breast, lung, colon, and squamous cell cancers. Recent studies showed HBs in meningioma, in the cyst fluid of craniopharyngioma, in the cerebrospinal fluid (CSF) of pediatric patients with posterior fossa tumors, and in glioblastoma cell lines. Hemorphins, abundant brain peptides formed via HB-chain cleavage, exert opioid activity and antiproliferative and immunomodifier effects. Hence mutations in HBs may modify brain tumorigenesis via influencing hemorphins and perturbing regulations of immune surveillance and cell growth in the neuroectodermal tissues. The β-globin gene cluster resides in the chromosome region 11p15.5, harboring important immunity genes and IGF2, H19, PHLDA2/TSSC3, TRIM3, and SLC22A18 genes associated with cancers and gliomas. 11p15.5 is a prominent region subject to epigenetic regulation. Thus the β-globin loci may exert haplotypal interactions with these. Some clues support this theory. It is well established that iron load induces liver cancer in thalassemia major; however iron load-independent associations also exist. Enhanced rates of hematologic malignancies are associated with HB Lepore, association of hemoglobin E with cholangiocarcinoma, and enhanced gastric cancer rates in the thalassemia trait. In the African Herero population, a mutant form of δ-globin is very prevalent, and this population has higher rates of pediatric brain tumors. Globins are also expressed in healthy endothelia and in tumoral vessels, indicating potential involvement in angiogenesis. Studies on HBs and their cleavage peptides in cancers and brain tumors may lead to innovative treatment strategies.

Colloid cysts appear most commonly in the third ventricle, their occurrence in the sellar region is uncommon. The authors report a female patient with a pituitary colloid cyst. She was diagnosed incidentally with a sellar lesion by a routine paranasal computed tomography examination performed for planning of a dental implant surgery. Radiologic examinations revealed a pituitary lesion that was removed by transnasal transsphenoidal route. Her pathologic examination revealed that the lesion was a colloid cyst. Although rare, colloid cysts should be considered in the differential diagnosis of pituitary lesions

OBJECTIVERecent studies have established that hemispheric diffuse gliomas may be grouped into subsets on the basis of molecular markers; these subsets are loosely correlated with the histopathological diagnosis but are strong predictors of clinical tumor behavior. Based on an analysis of molecular and clinical parameters, the authors hypothesized that mutations of the telomerase promoter (TERTp-mut) mark separate oncogenic programs among isocitrate dehydrogenase 1 and/or 2 (IDH) mutant (IDH-mut) and IDH wild-type (IDH-wt) diffuse gliomas independent of histopathology or WHO grade.METHODSFour molecular subsets of the combined statuses of IDH and TERT-promoter mutations (double mutant, IDH only, TERT only, and double negative) were defined. Differences in age, anatomical location, molecular genetics, and survival rates in a surgical cohort of 299 patients with a total of 356 hemispheric diffuse gliomas (WHO Grade II, III, or IV) were analyzed.RESULTSTERTp-mut were present in 38.8% of IDH-mut and 70.2% of IDH-wt gliomas. The mutational status was stable in each patient at 57 recurrence events over a 2645-month cumulative follow-up period. Among patients with IDH-mut gliomas, those in the double-mutant subset had better survival and a lower incidence of malignant degeneration than those in the IDH-only subset. Of patients in the double-mutant subset, 96.3% were also positive for 1p/19q codeletions. All patients with 1p/19q codeletions had TERTp-mut. In patients with IDH-mut glioma, epidermal growth factor receptor or phosphatase and tensin homolog mutations were not observed, and copy-number variations were uncommon. Among IDH-wt gliomas, the TERT-only subset was associated with significantly higher age, higher Ki-67 labeling index, primary glioblastoma-specific oncogenic changes, and poor survival. The double-negative subset was genetically and biologically heterogeneous. Survival analyses (Kaplan-Meier, multivariate, and regression-tree analyses) confirmed that patients in the 4 molecular subsets had distinct prognoses.CONCLUSIONSMolecular subsets result in different tumor biology and clinical behaviors in hemispheric diffuse gliomas.

Objectives Unpaid carers have many and varied responsibilities in society, which can include medication management for the person they support. However, the potential for Australian community pharmacies to better assist carers is relatively unexplored. This mixed-methods study investigated the acceptability of a local carer support service by trained community pharmacy staff, including issues regarding the implementation and impact of this service. Methods Staff from 11 community pharmacies in South East Queensland, Australia, were trained to deliver a six-step carer support service between September 2016 and March 2017. Pharmacies were supported by a carer and pharmacist mentor pair and asked to recruit up to six carers each. Evaluations of staff training were descriptively analysed. Semi-structured interviews were undertaken with pharmacy staff, and interview transcripts were analysed thematically. Key findings Staff training evaluations were positive; participants acquired new information about carers and rated the service highly in terms of its importance within the pharmacy setting. Feedback was obtained on how to improve the training, such as further opportunities for role-play. Seven staff members were interviewed, and data analysis revealed two main themes: (1) implementation of the carer support service and (2) perceived impact on pharmacy staff. Positive attitudes towards recognising and supporting carers, and training and mentoring were identified with community pharmacies viewed as a suitable place for delivering this new service. New insights into the impact of caring were widely reported, which staff had not appreciated from previous carer interactions. Structural issues, including space and time pressures, and a lack of awareness about the types of support currently available to carers were emphasised. Conclusion Pharmacy staff are well positioned to support carers. Engaging carers in conversation to better understand their needs is a small step with potential for big gains, including a more empathetic understanding of their individual circumstances and overall well-being.

Background: To optimize positive outcomes, the design of new pharmacy services should consider the preferences of consumers with chronic condition(s) and their carers. Objectives: (i) To evaluate the relative importance of community pharmacy service characteristics, from the perspective of consumers with chronic condition(s) and carers; (ii) To compare consumer and carer preferences to health professional beliefs about ideal service characteristics for consumers. Method: A discrete choice experiment was completed by consumers with chronic condition(s) and/or carers (n = 602) and health professionals (n = 297), recruited from four regions in Australia. Participants were each randomized to one survey version containing four (from a total 72) different choices between two new pharmacy services. Consumer and carer participants were also given an ‘opt out’ alternative of current service. Each service was described using six attributes related to pharmacy service characteristics: continued medicines supply, continuity and coordinated care, location, medication management, education and information, and cost. Results: Consumers and carers placed highest priority on continued medicines supply by a pharmacist for regular and symptom flare up medicines (100 priority points), a pharmacy located within a ‘one-stop’ health center (61 points) and home delivery of medicines (52 points). Although continued medicines supply was most important for consumers and carers, pharmacy location was perceived by health professionals to be the most important characteristic for consumers. Participants were less inclined to choose new services if their current pharmacy offered high quality services that were person-centered, easy to access and responsive to their needs. Younger, more highly educated and employed participants, and those with established condition(s) were more likely to choose new services. Conclusions: Person-centered care is a fundamental tenet for pharmacy services. The provision of continued medicines supply (e.g. through pharmacist prescribing), convenient and coordinated care delivered through a one stop health centre, and home delivery of medicines, should be prioritized when planning pharmacy services to best assist consumers to manage chronic conditions.

Aggressive pituitary adenomas have a high risk of recurrence, a lack of therapeutic response, and resistance to conventional treatment. So far, no satisfactory biomarkers are available for predicting their behavior. Some specific pituitary adenoma histotypes are more prone to follow an aggressive behavior. Pituitary carcinomas are rare and show cerebrospinal and/or systemic metastasis. They have worse prognosis than aggressive adenomas, and radiation is of limited use in their treatment.

Background: The germ tube test (GTT) is inexpensive, easy, and well‑defined test that differentiates Candida albicans (excluding Candida dubliniensis and Candida africana) from other species. The aim of this study was to evaluate various serums (i.e., human, rabbit, horse, and fetal bovine serum) used in the GTT and Mueller‑Hinton agar (MHA).Materials and Methods: Fifty species isolated from various clinical samples that were defined as C. albicans by both conventional and DNA sequence analysis methods were included in the study. One to two colonies of C. albicans were mixed into 0.5–1 ml of fetal bovine serum, horse serum, rabbit serum, and human serum. Serums and MHA were incubated at 37°C for GTT. They were removed from the incubator and evaluated after 30 min, 1 h, 2 h, and 3 h of incubation. The GTT was accepted to be positive only if germ tube was 1/2 the width and 3 times the length of the parent yeast cell and with no constriction at the point of origin.Results: When the use of serums and MHA for GTT was statistically evaluated, according to the positive scoring, the best results were obtained with MHA and with rabbit, horse, and fetal bovine serum, respectively. The best definition over time statistically was the third hour.Conclusion: It is suggested that inexpensive MHA is a fast, appropriate, and reliable medium for the probable diagnosis of GTT and C. albicans; however, additional studies are still needed to define other Candida species.Keywords: Candida albicans, germ tube test, Mueller‑Hinton agar, sequencing

The feasibility of an individualised carer support service delivered in community pharmacies was assessed from the perspective of carer participants using a pre-post questionnaire and semistructured interviews. Eligible pharmacies were required to offer a medication management service relevant to carers and have a semiprivate space for conversations. Carers were required to self-identify as an unpaid support person for someone with a chronic condition or disability. Between September 2016 and March 2017, staff from 11 community pharmacies in South-East Queensland, Australia were trained, and provided with ongoing mentoring from a pharmacist and carer to support service implementation. Identification of carers and support to achieve a personal and care-giving goal were key features of the service. Questionnaires included the EQ-5D-3L, the Bakas Caregiving Outcomes Scale, and questions relating to goal achievement, carer roles, and responsibilities. Seven follow-up carer interviews were undertaken between March and May 2017 and analysed thematically. Pre-post questionnaires were available for 17 carers (one withdrew, two incomplete). Of the 29 goals set, 10 were achieved and 14 partially achieved. EQ-5D-3L scores were unchanged, while 7 of the 15 items comprising the Bakas score improved (p < 0.05). Carer service evaluation was generally favourable, and these two main interview themes were the impact of caring and pharmacy experience. The impact of caring, while variable, was significant. Pharmacy experiences were mostly positive and the opportunity for carers to further engage with pharmacy staff was appreciated. The service was feasible and initial reported benefits to carers may support further research potentially in terms of a larger controlled trial.

PubMedID: 28204594 Candida parapsilosis, although a human commensal, acts as an opportunistic pathogen associated with nosocomial infections, with a rising incidence worldwide. Its ecological characteristics are poorly understood. Human-made environments within dwellings, such as dishwashers and water distribution systems, represent major sources of fungi such as C. parapsilosis. Here, we investigated the presence of members of the C. parapsilosis complex in 99 washing machines in various dwellings in the city of Mersin, Turkey. We sampled three sites in each washing machine: (i) the washing powder drawers, (ii) fabric softener drawers, and (iii) rubber seals around the washing machine doors. Additionally, we recorded the type of cleanser used by each customer. Of note, 25.3% of sampled washing machines harbored C. parapsilosis strains, later identified as the members of the C. parapsilosis sensu stricto via internal transcribed spacer (ITS) sequencing. Out of the 29 isolates obtained, biofilm-forming ability and proteinase and esterase activities were recorded in 14, 11, and 4 of the isolates, respectively. Our results suggest that the washing machines investigated abundantly harbored C. parapsilosis sensu stricto; however, no single preferred isolation site or association with cleanser type was observed (P > .05). Furthermore, C. parapsilosis isolates grew at temperatures ranging from 10°C to 37°C, at pH values ranging from 4 to 10, and were found to tolerate 5-10% NaCl. Domestic laundry appliances as a potential source of C. parapsilosis infections are discussed. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved.

Precise tiered tumor grading is essential for predicting prognosis, selecting different treatment options and for follow-up of brain tumor patients. Ki67 labeling index (LI) is widely employed in assessing aggressiveness of glial brain tumors. However, Ki67 is subject to interlaboratory variability, and its antigen is expressed on all cell cycle phases except G0, which hinders its usage as a precise criterion for assessing cell proliferation. Indeed, there exist peculiar observations pertinent to increases of Ki67 index in glial tumors following radiotherapy or treatment with tyrosine kinase inhibitors. Moreover, we have witnessed a reduced Ki67 labeling in a gemistocytic glioma during its rapid recurrence under temozolomide treatment. Therefore, we reviewed pitfalls in employing Ki67 indices for predicting glial tumor biology and tried to answer whether the mitotic marker PHH3 (phosphorylated histone H3) could provide additional information in predicting glial tumor biology. PHH3-based assessment of proliferating cell fraction provides novel potentials, but it has also its own weaknesses. It has not yet been determined whether it would be more advantageous to report: a mitotic count (MC) per unit-area (e.g., 10 high power fields (HPF)) or a mitotic index (MI) (per 1,000 tumor cells). Further, there exist peculiarities in terms of unexpectedly low or high PHH3 values in pilocytic astrocytomas and angiocentric gliomas, respectively. Indeed, we encountered almost no staining with PHH3 in our unique gemistocytic astrocytoma case. Hence, at least in some glial malignancies, PHH3 may not be necessary for cell proliferation. Awareness of the weaknesses of proliferation markers in brain tumors may improve patient monitoring and treatment. .

Background The past decades have witnessed a rapid evolution of research on evidence-based acute stroke care interventions worldwide. Nonetheless, the evidence-to-practice gap in acute stroke care remains variable with slow and inconsistent uptake in low-middle income countries (LMICs). This review aims to identify and compare evidence-based acute stroke management interventions with alternative care on overall patient mortality and morbidity outcomes, functional independence, and length of hospital stay across Africa. Methods This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. An electronic search was conducted in six databases comprising MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Academic Search Complete and Cochrane Library for experimental and non-experimental studies. Eligible studies were abstracted into evidence tables and their methodological quality appraised using the Joanna Briggs Institute checklist. Data were analysed and presented narratively with reference to observed differences in patient outcomes, reporting p values and confidence intervals for any possible relationship. Results Initially, 1896 articles were identified and 37 fully screened. Four non-experimental studies (three cohort and one case series studies) were included in the final review. One study focused on the clinical efficacy of a stroke unit whilst the remaining three reported on thrombolytic therapy. The results demonstrated a reduction in patient deaths attributed to stroke unit care and thrombolytic therapy. Thrombolytic therapy was also associated with reductions in symptomatic intracerebral haemorrhage (SICH). However, the limited eligible studies and methodological limitations compromised definitive conclusions on the extent of and level of efficacy of evidence-based acute stroke care interventions across Africa. Conclusion Evidence from this review confirms the widespread assertion of low applicability and uptake of evidence-based acute stroke care in LMICs. Despite the limited eligible studies, the overall positive patient outcomes following such interventions demonstrate the applicability and value of evidence-based acute stroke care interventions in Africa. Health policy attention is thus required to ensure widespread applicability of such interventions for improved patients’ outcomes. The review findings also emphasises the need for further research to unravel the reasons for low uptake. Systematic review registration PROSPERO CRD42016051566 Electronic supplementary material The online version of this article (10.1186/s13643-017-0594-4) contains supplementary material, which is available to authorized users.

Although the frequency of candidal onychomycosis is increasing daily, there is little information in literature about the epidemiology, pathogenesis, and antifungal susceptibility of this dermatological disease. This study aimed to provide information about the epidemiology, pathogenesis, and azole susceptibility of Candida species isolated from patients living in a region with continental climate. After identification of the isolated strains using conventional methods, proteinase and phospholipase activities were determined by a plate method and biofilm-forming ability was determined using the microplate method. Susceptibility of the same species to fluconazole (FLU), voriconazole (VRC), miconazole (MNZ), itraconazole (ITZ), and ketoconazole (KTZ) were determined by microdilution method. The 50 Candida isolates included 23 C. parapsilosis (46%), 13 C. albicans (26%), 4 C. guilliermondii(8%), 4 C.tropicalis (8%), 2 C.krusei(2%), 1 C.lusitaniae (2%), 1 C. sake (2%), and 1 C. kefyr (2%) isolates. The geometric mean (GM) of the minimum inhibitory concentration (MIC) for FLU, KTZ, VRC, MNZ, and ITZ was 0.4 μg/mL, 0.08 μg/mL, 0.08 μg/mL, 0.2 μg/mL, and 0.6 μg/mL, respectively. Proteinase, phospholipase, and biofilm-forming ability were detected in 18%(9/50), 20%(10/50), and 6%(3/50) of the Candida isolates, respectively. We found that the most frequently isolated species is C.parapsilosis. On the basis of the GM values, the most effective azoles are ketoconazole and voriconazole. The isolated Candida species exhibited low phospholipase, proteinase, and biofilm formation activities.