Editorial: Immersive media in connected health-volume II.

Immersive media, particularly Extended Reality (XR), is at the forefront of revolutionizing the healthcare industry. Healthcare provides XR with "silver bullet" use cases that add value and societal effect to the technology. Healthcare interventions frequently require imaging or visualization to be applied correctly, and the sensation of presence that XR can provide is crucial as a training aid for healthcare learners. From anatomy to surgical training, multimodal immersion in the reality of a medical situation increases the impact of an XR resource compared to the usual approach. Thus, healthcare has become a specialized focus for the immersive media sector, with a multitude of development and research underway. This research subject, which followed on from the previous one, yielded an eclectic group of works spanning the gamut of immersive media applications in healthcare. The underlying theme in these works remains a consistent focus on calibrating, validating, verifying, and standardizing procedures, instruments, and technologies in order to constantly rigorously streamline the means and materials that will integrate immersive technologies in healthcare. In that spirit, we share the findings from this research topic as a motivator for rigorous and evidence-based use of immersive media in digital and connected health.

Morbidity after local excision of the transformation zone for cervical intra-epithelial neoplasia and early cervical cancer.

The awareness that cervical intra-epithelial neoplasia (CIN) treatment increases the risk of preterm birth has led to major changes in clinical practice. Women with CIN have a higher baseline risk of prematurity but local treatment further increases this risk. The risk further increases with increasing cone length and multiplies for repeat excisions; it is unclear whether small cones confer any additional risk to CIN alone. There is no evidence to suggest that fertility is affected by local treatment, although this increases the risk of mid-trimester loss. Caution should prevail when deciding to treat women with CIN of reproductive age. If treatment is offered, this should be conducted effectively to optimise the clearance of disease and minimise the risk of recurrence. Colposcopists should alert women undergoing treatment that this may increase the risk of preterm birth and that they may be offered interventions when pregnant. The cone length should be clearly documented and used as a risk stratifier.

Spontaneous miscarriages in patients with bladder pain syndrome/interstitial cystitis - effect of stress on inflammation?

Interstitial cystitis/painful bladder syndrome (IC/PBS) affects mostly women and is characterized by pelvic pain or pressure and frequency of voiding in the absence of urinary tract infection. Acute stress worsens IC/PBS symptoms and bladder inflammation associated with increased number of activated mast cells. We investigated retroactively the incidence of spontaneous miscarriages and any related stress in IC/PBS patients. A questionnaire was posted on an IC/PBS website and patients visiting the site were invited to complete and file it electronically. Limitations include the lack of defined diagnosis of those responding, and of a validated stress questionnaire. There were 193 respondents (mean age = 37.3 years) over two weeks. Of those responding, 87% (mean age = 33.2 years) had received a diagnosis of IC/PBS. Of those respondents with IC/PBS, 76% reported having had miscarriages: (a) 55% had one miscarriage, (b) 26% had two, and (c) 23% had three or more. These rates are much higher than those of in the general population: 10-20% with one and 1-2% with habitual spontaneous miscarriages. The majority of patients (78%) reported experiencing significant stress. IC/PBS patients appear to have a much high incidence of spontaneous miscarriages compared to the general population. Most patients reported experiencing stress that has been associated with miscarriages. This finding may be explained via stress stimulating bladder and uterine immune cells, especially mast cells, inhibition of which by the natural flavonoid luteolin may be beneficial.

Advances in biofeedback and neurofeedback studies on smoking.

Smoking is a leading cause of morbidity and premature death constituting a global health challenge. Although, pharmacological and behavioral approaches comprise the mainstay of smoking cessation interventions, the efficacy and safety of pharmacotherapy is not demonstrated for some populations. Non-pharmacological approaches, such as biofeedback (BF) and neurofeedback (NF) could facilitate self-regulation of predisposing factors of relapse such as craving and stress. The current review aims to aggregate the existing evidence regarding the effects of BF and NF training on smokers. Relevant studies were identified through searching in Scopus, PubMed and Cochrane Library, and through hand-searching the references of screened articles. Peer-reviewed controlled and uncontrolled studies, where BF and/or NF training was administered, were included and evaluated according to PICOS framework. Narrative qualitative synthesis of ten eligible studies was performed, aggregated into three categories according to training provided. BF outcomes seem to be affected by smoking behavior prior to training; individualized EEG NF training holds promise for modulating craving-related response while minimizing the required number of sessions. Real-time fMRI NF studies concluded that nicotine-dependent individuals could modulate craving-related brain responses, while mixed results were revealed regarding smokers' ability to modulate brain responses related to resistance towards the urge to smoke. BF and NF training seem to facilitate modulation of autonomous and/or central nervous system activity while also transferring this learned self-regulation to behavioral outcomes. BF and NF training should a) address remaining issues on specificity and scientific validity, b) target diverse demographics, and c) produce robust reproducible methodologies and clinical guidelines for relevant health care providers, in order to be considered as viable complementary tools to standard smoking cessation care.

HPV vaccination and cancer prevention.

Prophylactic vaccines have been found to be highly effective in preventing infection and pre-invasive and invasive cervical, vulvovaginal and anal disease caused by the vaccine types. HPV vaccines contain virus-like particles that lack the viral genome and produce high titres of neutralising antibodies. Although the vaccines are highly effective in preventing infections, they do not enhance clearance of existing infections. Vaccination programmes target prepubertal girls and boys prior to sexual debut as efficacy is highest in HPV naïve individuals. School-based programmes achieve higher coverage, although implementation is country specific. Vaccination of older women may offer some protection and acceleration of impact, although this may not be cost-effective. HPV-based screening will continue for vaccinated cohorts, although intervals may increase.

Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature.

BACKGROUND: Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population. MATERIALS AND METHODS: Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment. DATA SYNTHESIS: Summary effects were estimated using random-effects models. OUTCOMES: Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population. RESULTS: Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22-69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57-4.24; P < 0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58-21.10; P < 0.001), vulvar (3.34, 2.39-4.67; P < 0.001), and anal cancer (5.11, 2.73-9.55; P < 0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69-36.94; P = 0.073). CONCLUSIONS: Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.

Does the Pittsburgh Severity Score predict outcome in esophageal perforation?

Esophageal perforation is an uncommon and challenging surgical emergency associated with high rates of morbidity and mortality. At present, no consensus exists on optimal management of the condition. The Pittsburgh Severity Score (PSS) is a tool intended to stratify perforation severity and guide treatment. However, there is a paucity of literature examining the validity of the score or its application in a UK population. This study aims to validate the PSS and explore its use in stratifying patients with esophageal perforation into distinct subgroups with differential outcomes in an independent UK study population.All patients treated for esophageal perforation at Queen Elizabeth Hospital, Birmingham between September 2003 and October 2017 were included in this study. Cases were identified using a combination of ICD-10 and OPCS informatics search codes and prospective case collection. Data relating to the clinical presentation, diagnosis, management, and outcome of cases were recorded using a preformed data collection form. PSS predictive performance was assessed against five outcomes: rates of post-perforation and post-operative complications, in-hospital mortality, length of intensive care (ICU/HDU) stay, and total length of hospital stay.A total of 87 cases were identified, consisting of 48 (55%) iatrogenic perforations, 24 (28%) cases of spontaneous (Boerhaave's) perforation, and 15 perforations due to other etiologies (17%). Operative management was favored in this series, with 47% of all perforations being treated surgically. Overall in-hospital mortality was 13%, coupled with a median length of hospital stay of 24 days (interquartile range [IQR]: 12-49), of which a median of 2 days was spent in intensive care facilities (IQR: 0-14). A total of 46% of patients developed post-perforation complications, with 59% of the operatively managed cohort developing complications post-operatively.The PSS was not found to be significantly predictive of post-perforation complications (area under the ROC curve [AUROC]: 0.62, p = 0.053) or in-hospital mortality (AUROC: 0.69, p = 0.057) for the cohort as a whole. However, a subgroup analysis found the accuracy of the PSS to vary considerably by etiology, being significantly predictive of post-perforation complications within the subgroup of Boerhaave's perforations (AUROC: 0.86, p = 0.004).In conclusion, we found that the PSS has some utility in stratifying esophageal perforation severity and predicting specific patient outcomes. However, it appears to be of more value when applied to the subgroup of patients with Boerhaave's perforations.

Amniotic fluid lactic acid and matrix metalloproteinase-8 levels at the time of fetal surgery for a spine defect: association with subsequent preterm prelabour rupture of membranes.

OBJECTIVE: In utero fetal surgery to correct incomplete closure of the spinal cord lessens the extent of permanent damage but is associated with preterm prelabour rupture of membranes (PPROM). We determined whether compounds in amniotic fluid collected at the time of surgery predicted subsequent development of PPROM. DESIGN: Prospective study. SETTING: Hospitals in Sao Paulo, Brazil. POPULATION: Twenty-four consecutive pregnant women at 24-26 weeks of gestation seen between February and October 2017 with a singleton pregnancy underwent in utero surgery to correct an open spinal defect in their fetus. METHODS: Amniotic fluid was tested for lactic acid, matrix metalloproteinase 2 (MMP-2), MMP-8, MMP-9 and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay. Clinical data were collected after completion of all laboratory studies. MAIN OUTCOME MEASURE: Amniotic fluid concentration of compounds in women with or without PPROM. RESULTS: Preterm prelabour rupture of membranes occurred in seven (29.2%) women. There were no differences in maternal age, gravidity, parity, race, history of caesarean sections or fetal gender between women with or without PPROM. Length of surgery, days of wound healing and length of hospital stay were also indistinguishable. The median concentrations of MMP-8 (1.7 versus 0.6 ng/ml; P = 0.0041) and lactic acid (7.1 versus 5.9 mm; P = 0.0181) were higher in women with PPROM. The amniotic fluid MMP-8 level was also negatively correlated with gestational age at delivery (Spearman r = -0.4217, P = 0.0319). CONCLUSION: Differences in susceptibility to develop PPROM are present before fetal surgery. An increase in anaerobic glycolysis, evidenced by the intra-amniotic lactic acid level, may enhance MMP-8 production and weaken maternal and fetal membranes. TWEETABLE ABSTRACT: Matrix metalloproteinase-8 and lactic acid in amniotic fluid predict preterm prelabour rupture of membranes.

Targeting histone deacetylases in endometrial cancer: a paradigm-shifting therapeutic strategy?

OBJECTIVE: Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies. Recently, a family of compounds that alter epigenetic expression, namely histone deacetylase inhibitors, have shown promise as possible therapeutic agents in endometrial cancer. The present review aims to discuss the therapeutic potential of these agents. MATERIALS AND METHODS: This literature review was performed using the MEDLINE database; the search terms histone, deacetylase, inhibitors, endometrial, targeted therapies for endometrial cancer were employed to identify relevant studies. We only reviewed English language publications and also considered studies that were not entirely focused on endometrial cancer. Ultimately, sixty-four articles published until January 2018 were incorporated into our review. RESULTS: Studies in cell cultures have demonstrated that histone deacetylase inhibitors exert their antineoplastic activity by promoting expression of p21WAF1 and p27KIP1, cyclin-dependent kinase inhibitors, that have important roles in cell cycle regulation; importantly, the transcription of specific genes (e.g., E-cadherin, PTEN) that are commonly silenced in endometrial cancer is also enhanced. In addition to these abstracts effects, novel compounds with histone deacetylase inhibitor activity (e.g., scriptaid, trichostatin, entinostat) have also demonstrated significant antineoplastic activity both in vitro and in vivo, by liming tumor growth, inducing apoptosis, inhibiting angiogenesis and potentiating the effects of chemotherapy. CONCLUSIONS: The applications of histone deacetylase inhibitors in endometrial cancer appear promising; nonetheless, additional trials are necessary to establish the therapeutic role, clinical utility, and safety of these promising compounds.

Successful combined surgical approach in a rare case of retrotracheal goitre in a patient with anatomical impediments.

Diving goitres can descend the cervical region expanding directly into the thoracic cavity. In most cases, diving goitres extend into the anterosuperior compartment, but they may also extend behind the trachea. We herein present a case of a male patient with retrotracheal goitre and history of left thyroid lobectomy and median sternotomy for thoracic aortic aneurysm repair with graft placement. After detailed preoperative evaluation, the patient underwent surgical resection of the mass through a combined approach; the existing cervical incision and a right posterolateral mini-thoracotomy. The postoperative course of the patient was uncomplicated. One year after surgery, the patient is asymptomatic and disease-free. (Folia Morphol 2018; 77, 1: 166-169).

The role of prasugrel in the management of acute coronary syndromes: a systematic review.

OBJECTIVE: Dual antiplatelet therapy (DAPT) is the treatment of choice in the medical management of patients with acute coronary syndrome (ACS). The combination of aspirin and a P2Y12 inhibitor in patients who receive a coronary stent reduces the rate of stent thrombosis and the rates of major adverse cardiovascular events. However, patients with acute coronary syndrome remain at risk of recurrent cardiovascular events despite the advance of medical therapy. The limitations of clopidogrel with variable antiplatelet effects and delayed onset of action are well established and lead to the development of newer P2Y12 inhibitors. Prasugrel is a selective adenosine diphosphate (ADP) receptor antagonist indicated for use in patients with ACS. Prasugrel provides greater inhibition of platelet aggregation than clopidogrel and has a rapid onset of action. We have conducted a systematic review to retrieve current evidence regarding the role of prasugrel in the management of ACS. Evidence comparing prasugrel, clopidogrel, and ticagrelor remain scant. MATERIALS AND METHODS: A complete literature survey was performed using PubMed database search to gather available information regarding management of acute coronary syndromes and prasugrel. An explorative comparison of the safety and efficacy of prasugrel, clopidogrel, and ticagrelor was also conducted. RESULTS: Prasugrel and ticagrelor are more efficacious than clopidogrel in reducing the occurrence of non-fatal myocardial infarction, stroke, or cardiovascular (CV) death but they have also an increased risk of major bleeding in comparison to clopidogrel. CONCLUSIONS: Prasugrel and ticagrelor are today the recommended first-line agents in patients with ACS. The estimation of which drug is superior over the other cannot be reliably established from the current trials.

Renal paratransplant hernia revealed: a review of the literature.

BACKGROUND: Renal paratransplant hernia (RPH) is an uncommon variant of internal hernias developed in renal transplant recipients. The aim of this review is to meticulously present and analyze all data coming mainly from case reports or short-case studies on this very uncommon surgical entity. MATERIALS AND METHODS: The MEDLINE/PubMed database was searched for publications with the medical subject heading ''renal paratransplant hernia''. All the references from the identified articles were searched for relevant information. The end date of the literature search was set to March 2016. RESULTS: Our search revealed five publications, three short clinical series (three cases each) and two case reports. The total number of cases retrieved was 11. RPH should be considered as an iatrogenic surgical complication. The incidence is around 0.45%. CONCLUSIONS: RPH is a relatively uncommon but potentially fatal complication after renal transplantation, and its non-specific symptoms may lead to misdiagnosis. Physician awareness, prompt diagnosis, and early surgical intervention are critical. In addition, meticulous surgical technique during transplantation may help avoid this complication.

Advances in thymic carcinoma diagnosis and treatment: a review of literature.

Thymomas account for up to 50 % of anterior mediastinal neoplasms with an incidence of 0.13 per 100,000 person-years in the USA. Thymic carcinoma is a rare malignancy of the thymus gland distinguished from thymomas as it has a more invasive and metastasizing potential conferring poor prognosis. Due to the rarity of thymic carcinoma and the great variety of its histological subtypes, there is no solid evidence on optimal staging, imaging and treatment guidelines. Herein, we systematically review the literature on current clinical practice with regard to diagnostic evaluation, histopathological assessment, management and treatment of squamous thymic carcinoma.

Complex cystic breast masses in ultrasound examination.

Complex cystic masses are defined as lesions composed of anechoic (cystic) and echogenic (solid) components, unlike complicated cysts, the echogenic fluid content of which imitates a solid lesion. Complex masses are classified as ACR4 and require histological verification by percutaneous biopsy and/or surgical ablation. The etiology is diverse, and can be benign or high risk (an abscess, hematoma, fat necrosis, fibrocystic mastopathy, a phyllodes tumor, papilloma) as much as malignant (papillary cancer, necrotic cancer, a ductal carcinoma in situ, metastases). The biopsy technique must be adapted to each case and it is often necessary to insert a coil during the procedure. Histopathological correlation is essential to ensure that the samples are representative and concur with the ultrasound appearance, so as not to fail to recognize high risk or malignant lesions requiring appropriate management.

In vitro activity of cadazolid against clinically relevant Clostridium difficile isolates and in an in vitro gut model of C. difficile infection.

OBJECTIVES: We investigated the in vitro activity of cadazolid against 100 Clostridium difficile isolates and its efficacy in a simulated human gut model of C. difficile infection (CDI). METHODS: MICs of cadazolid, metronidazole, vancomycin, moxifloxacin and linezolid were determined using agar incorporation for 100 C. difficile isolates, including 30 epidemic strains (ribotypes 027, 106 and 001) with reduced metronidazole susceptibility, 2 linezolid-resistant isolates and 2 moxifloxacin-resistant isolates. We evaluated the efficacy of two cadazolid dosing regimens (250 versus 750 mg/L twice daily for 7 days) to treat simulated CDI. Microflora populations, C. difficile total viable counts and spores, cytotoxin titres, possible emergence of cadazolid, linezolid or quinolone resistance, and antimicrobial concentrations were monitored throughout. RESULTS: Cadazolid was active against all (including linezolid- and moxifloxacin-resistant) C. difficile strains (MIC90 0.125, range 0.03-0.25 mg/L). The cadazolid geometric mean MIC was 152-fold, 16-fold, 9-fold and 7-fold lower than those of moxifloxacin, linezolid, metronidazole and vancomycin, respectively. Both cadazolid dosing regimens rapidly reduced C. difficile viable counts and cytotoxin with no evidence of recurrence. Cadazolid levels persisted at 50-100-fold supra-MIC for 14 days post-dosing. Cadazolid inhibition of enumerated gut microflora was limited, with the exception of bifidobacteria; Bacteroides fragilis group and Lactobacillus spp. counts were unaffected. There was no evidence for selection of strains resistant to cadazolid, quinolones or linezolid. CONCLUSIONS: Cadazolid activity was greater than other tested antimicrobials against 100 C. difficile strains. Cadazolid effectively treated simulated CDI in a gut model, with limited impact on the enumerated gut microflora and no signs of recurrence or emergence of resistance within the experimental timeframe.

ShearWave™ Elastography BE1 multinational breast study: additional SWE™ features support potential to downgrade BI-RADS®-3 lesions.

PURPOSE: To determine the benefit of ShearWave™ Elastography (SWE™) in the ultrasound characterization of BI-RADS® 3 breast lesions in a diagnostic population. MATERIALS AND METHODS: 303 BI-RADS® 3 lesions (mean size: 13.2 mm, SD: 7.5 mm) from the multicenter BE1 prospective study population were analyzed: 201 (66%) had cytology or core biopsy, and the remaining 102 had a minimum follow-up of one year; 8 (2.6%) were malignant. 7 SWE features were evaluated with regard to their ability to downgrade benign BI-RADS® 3 masses. The performance of each SWE feature was assessed by evaluating the number of lesions correctly reclassified and the impact on cancer rates within the new BI-RADS® 3' lesion group. RESULTS: No malignancies were found with an E-color "black to dark blue", which allowed the downgrading of 110/303 benign masses (p < 0.0001), with a non-significant increase in BI-RADS® 3' malignancy rate from 2.6% to 4.1%. E-max ≤ 20 kPa (2.6 m/s) was able to downgrade 48/303 (p < 0.0001) lesions with a lower increase in BI-RADS® 3' malignancy rate (3.1%). No other SWE features were useful for reclassifying benign BI-RADS® 3 lesions. CONCLUSION: Applying simple reclassification rules, SWE assessment of the maximum stiffness of lesions allowed the downgrading of a sub-group of benign BI-RADS® 3 lesions. This was accompanied by a non-significant increase in the malignancy rate in the new BI-RADS® 3 class.