The role of non-oropharyngeal biopsies in head and neck squamous cell carcinoma of unknown primary: A systematic review.

INTRODUCTION: This systematic review aims to evaluate the role of biopsies in non-oropharyngeal subsites in patients with cervical metastasis from head and neck squamous cell carcinoma of unknown primary (HNSCCUP). METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles that encompassed non-oropharyngeal biopsies in HNSCCUP as part of the diagnostic work-up were selected and analysed. RESULTS: A comprehensive search strategy was used to search relevant literature in PubMed from inception to October 2021. Eleven articles out of 860 were included, comprising 990 patients. There are no randomised control trials comparing the outcomes of survival and or locoregional control between patients who have or have not undergone non-targeted biopsies of non-oropharyngeal sub-sites for HNSCCUP. Several retrospective studies which showed an extremely low yield from random biopsies (range of yield, 0%-9%) of non-oropharyngeal subsites. Even targeted biopsies showed a low yield (range of yield, 0.6%-16.6%) from non-oropharyngeal subsites. The primary site identified for Epstein-Barr virus (EBV) positive cervical lymph nodes with an unknown primary is mainly the nasopharynx (51.7%). Narrow band imaging (NBI) (sensitivity range, 64%-91%) helps in the detection of primaries to target biopsies in non-oropharyngeal subsites. CONCLUSIONS: On the basis of this systematic review, it is not appropriate to offer biopsies of clinically and radiologically normal upper aerodigestive tract mucosa at non-oropharyngeal sites. Offer nasopharyngeal biopsies when the cervical node sampling reveals EBV-positive metastasis. Where available, NBI should be used to help detect and target biopsies in non-oropharyngeal subsites.

Briefings in surgical teams: a pilot study of experiences and attitudes.

While healthcare should not be compared to other high reliability organisations (HROs), many lessons, attitudes, and transferable practices can be applied and adapted from them to improve patient safety and team morale. Despite briefings improving both patient safety and effective team working, some in healthcare have not valued or actively engaged with them, deeming them to be irrelevant. In this pilot study we explored the experiences of, and attitudes to, briefings using a 10-question Survey Monkey. This was promoted during a human factors session at the 2023 Association of Surgeons in Training Conference (ASiT) and at a large NHS trust. Questions were asked about the number of briefings per day, attitudes, engagement, and respondents' attitudes to them. In total, 109 responses were received. A total of 85% reported at least one briefing on a normal operating day, 65% felt them to be interactive, 67% reported that briefings were led by the most senior surgical team member, and 58% lasted four minutes or more. Eighteen per cent of respondents felt they were of little benefit, and 56% did not routinely de-brief at the end of the day. This study has highlighted variable attitudes to team briefings, with some colleagues still seeing them as a 'tick box' exercise. While culture has changed following the introduction of the WHO checklist, the importance of active engagement and education to improve the delivery and value of effective briefings cannot be overestimated. It is also an opportunity to create a 'safe space' for team members and to confirm zero tolerance for any inappropriate behaviour, including sexual misconduct.

Multi-Domain Interventions for Dementia Prevention - A Systematic Review.

OBJECTIVES: There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may individually or collectively be undertaken to increase one's odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia. DESIGN, SETTING AND PARTICIPANTS: This systematic literature review of multidomain lifestyle interventions for the prevention of cognitive decline and dementia followed the PRISMA guidelines. Clinical trials involving multidomain intervention (i.e., diet and physical activity, or without cognitive training) in older adults (≥ 49 years old) at higher risk of dementia were identified through 5 electronic databases (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus). A comprehensive search was performed to identify and retrieve publications until 15 November 2022. Trials were published in English. RESULTS: The included studies (n=15) assessed change in cognition in response to a multidomain lifestyle intervention. However, the cognitive outcome measures used in these studies were heterogeneous. Despite this heterogeneity, two thirds of the studies showed improvement in cognition following a multidomain intervention (n=10 with a total of 9,439 participants). However, five studies reported no improvement in cognition following the multidomain intervention. The most common form of dietary intervention included higher amount of fruit and vegetable intake; whole-grain cereal products instead of refined; low fat options in milk and meat products; and limiting sucrose intake to less than 50 g/day. Most clinical trial studies were powered to examining the effects of multidomain interventions in cognition but were not designed to test the contribution of individual domains (i.e., dietary changes, increased physical activity, or increased cognitive stimulation alone). CONCLUSION: This systematic review aimed to determine the effect of multimodal lifestyle interventions on cognitive outcomes in older adults at risk of dementia. We found that participants with conditions that may increase the risk of dementia, (e.g., hypertension, cardiovascular fragility) do benefit from multi-modal lifestyle changes including diet, physical activity, and cognitive training. Two thirds of studies using multidomain lifestyle interventions showed improvements in cognitive function. Trials with a focus on cognitive training, dietary improvement, and physical activity may prevent or delay cognitive decline in older adults including those at risk of developing dementia. Future studies should consider longer follow-up periods and adequate power to be able to examine the effects of each lifestyle component in the context of multimodal interventions.

Oral mucosal melanoma in situ: a case report and review of the literature.

Oral mucosal melanoma is a rare presentation of malignant melanoma with a 5-year survival rate of only 15%. Oral mucosal melanoma in situ (OMMIS) is its assumed precursor. This report describes one of only 20 documented cases of OMMIS and outlines how early clinical recognition resulted in prompt histopathological diagnosis and subsequent complete surgical excision. A literature review of existing reported cases, their management, and latest outcomes was also performed, highlighting this rare condition for consideration in the differential diagnosis of pigmented oral pathologies.

Unmasking of systemic lupus erythematosus in a patient with hemophagocytic lymphohistiocytosis- macrophage activation syndrome (HLA-MAS) and diffuse alveolar hemorrhage.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by macrophages and cytotoxic T cells with aberrant activation. The primary (genetic) form, which is caused by mutations that affect lymphocyte cytotoxicity and immune regulation, is most prevalent in children, whereas the secondary (acquired) form is prevalent in adults. Secondary HLH is commonly caused by infections or cancers, but it can also be caused by autoimmune disorders, in which case it is known as macrophage activation syndrome (MAS; or MAS-HLH). A 25-year-old female presented with a high-grade fever that lasted for two weeks. His laboratory results revealed pancytopenia, neutropenia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. Based on the clinical presentation and laboratory findings, a provisional diagnosis of HLH has been made. A HLH protocol was utilized to treat the patient. During the course of hospitalization, systemic lupus erythematosus (SLE) was identified as the underlying cause. She improved dramatically after receiving an immunosuppressive regimen of etoposide, cyclosporine, and dexamethasone according to HLH protocol-2004 with individualized modifications. The clinician should be aware that HLH may be the initial manifestation of underlying SLE. Early diagnosis and aggressive, individualized treatment are the key to improving outcomes.

Is telemedicine a holy grail in healthcare policy: clinicians' and patients' perspectives from an Apex Institution in Western India.

BACKGROUND: This study aimed to explore the perception of doctors regarding telemedicine consultations and the level of patient satisfaction with the services received through teleconsultations. METHODS: This cross-sectional study was conducted on clinicians who provided teleconsultations and patients who received teleconsultations in an Apex healthcare institution in Western India. Semi-structured interview schedules were used to record the quantitative and qualitative information. Clinicians' perceptions and patients' satisfaction were assessed using two different 5-point Likert scales. Data were analyzed using SPSS v.23 using non-parametric tests (Kruskal Wallis and Mann-Whitney U). RESULTS: A total of 52 clinicians who delivered teleconsultations and 134 patients who received teleconsultations from those doctors were interviewed in this study. For 69% of doctors, telemedicine was feasible to implement, and for the rest, it was challenging. Doctors believe telemedicine is convenient for patients (77%) and prevents the transmission of infection (94.2%). Difficulty in clinical evaluation (73%), communication (55.7%), network connectivity (34%), diagnosis and investigations (32%), and patients' e-illiteracy (32%) were the most common challenges faced by clinicians. Patients' experiences were positive in terms of ease of registration (82.1%), audio quality (100%), freedom to discuss medicine (94.8%), and comprehension of the diagnoses (88.1%). Patients expressed satisfaction with the length of the teleconsultation (81.4%), the advice and care they received (78.4%), and the manner and communication of the clinicians (78.4%). CONCLUSIONS: Though there were some challenges in the implementation of telemedicine, the clinicians perceived it quite helpful. The majority of the patients were satisfied with teleconsultation services. Difficulty in registration, lack of communication, and a deep-rooted mindset of physical consultations were the primary concerns from the patient side.

Attosecond field emission.

Field emission of electrons underlies great advances in science and technology, ranging from signal processing at ever higher frequencies1 to imaging of the atomic-scale structure of matter2 with picometre resolution. The advancing of electron microscopy techniques to enable the complete visualization of matter on the native spatial (picometre) and temporal (attosecond) scales of electron dynamics calls for techniques that can confine and examine the field emission on sub-femtosecond time intervals. Intense laser pulses have paved the way to this end3,4 by demonstrating femtosecond confinement5,6 and sub-optical cycle control7,8 of the optical field emission9 from nanostructured metals. Yet the measurement of attosecond electron pulses has remained elusive. We used intense, sub-cycle light transients to induce optical field emission of electron pulses from tungsten nanotips and a weak replica of the same transient to directly investigate the emission dynamics in real time. Access to the temporal properties of the electron pulses rescattering off the tip surface, including the duration τ = (53 as ± 5 as) and chirp, and the direct exploration of nanoscale near fields open new prospects for research and applications at the interface of attosecond physics and nano-optics.

Comparison between abdominal CT findings in intensive care unit (ICU) and non-ICU patients with Covid-19: experience from a tertiary care hospital.

Background: 16-66% of COVID-19 positive patients may have abdominal symptoms and findings in abdominal CT. The yield of abdominal CT scan in patients having abdominal complaints is not known. Objectives: The aim of this study was to explore the various abdominal imaging manifestations of COVID-19 and COVID-19 associated Mucormycosis (CAM) and to identify the relevant clinical and laboratory features associated with severity of the symptoms. Methods: A retrospective single centre observational study was performed at a tertiary care hospital in Northwest India. All consecutive patients who had COVID positive RT-PCR report and had undergone abdominal Computed Tomography scan from March 2020 to November 2021 for various abdominal complaints were included. Demographic data, CT images and reports and all relevant lab parameters were collected. Results: Out of 75 patients, positive abdominal findings were seen in 65 patients. Hepatobiliary findings were seen in 41.3% (31 of 75; OR=1.9) and bowel abnormalities were found in 37.3% (28 of 75; OR=2.1) of COVID-19 patients. 7 patients who had renal infarcts or bowel ischemia were found to have COVID-19 associated Mucormycosis on histopathology. Conclusion: Chest CT severity score was positively correlated with most of the abdominal manifestations in patients requiring ICU admission. Elevated D-dimer levels were significantly associated with abdominal symptoms.

Non-medicalization of medical science: Rationalization for future.

As we delve into the intricacies of human disease, millions of people continue to be diagnosed as having what are labelled as pre-conditions or sub-clinical entities and may receive treatments designed to prevent further progression to clinical disease, but with debatable impact and consequences. Endocrinology is no different, with almost every organ system and associated diseases having subclinical entities. Although the expansion of these "grey" pre-conditions and their treatments come with a better understanding of pathophysiologic processes, they also entail financial costs and drug adverse-effects, and lack true prevention, thus refuting the very foundation of Medicine laid by Hippocrates "Primum non nocere" (Latin), i.e., do no harm. Subclinical hypothyroidism, prediabetes, osteopenia, and minimal autonomous cortisol excess are some of the endocrine pre-clinical conditions which do not require active pharmacological management in the vast majority. In fact, progression to clinical disease is seen in only a small minority with reversal to normality in most. Giving drugs also does not lead to true prevention by changing the course of future disease. The goal of the medical fraternity thus as a whole should be to bring this large chunk of humanity out of the hospitals towards leading a healthy lifestyle and away from the label of a medical disease condition.

Heat Equilibration of Integer and Fractional Quantum Hall Edge Modes in Graphene.

Hole-conjugate states of the fractional quantum Hall effect host counterpropagating edge channels which are thought to exchange charge and energy. These exchanges have been the subject of extensive theoretical and experimental works; in particular, it is yet unclear if the presence of integer quantum Hall edge channels stemming from fully filled Landau levels affects heat equilibration along the edge. In this Letter, we present heat transport measurements in quantum Hall states of graphene demonstrating that the integer channels can strongly equilibrate with the fractional ones, leading to markedly different regimes of quantized heat transport that depend on edge electrostatics. Our results allow for a better comprehension of the complex edge physics in the fractional quantum Hall regime.

Multiphase computed tomography angiography (mCTA) derived source images in acute ischemic stroke: Beyond collaterals. Can it obviate the need for computed tomography perfusion (CTP)?

BACKGROUND AND PURPOSE: To compare Multiphase CT Angiography derived source images (mCTA-SI) in acute ischemic stroke (AIS) with CT Perfusion (CTP) derived automated color maps of cerebral blood flow (CBF) and cerebral blood volume (CBV) and to assess the comparability of mCTA-SI with CTP in the prediction of final radiological and clinical outcome. METHODS: This prospective single-centre observational study comprised of patients with AIS of the anterior circulation, presenting within 24 h and undergoing neuroimaging under stroke protocol with follow-up. Non-contrast computed tomography (NCCT), mCTA, and CTP were acquired with follow-up NCCT at 24 h and modified Rankin score (mRS) at 3 months. mCTA-SI and CTP color maps were scored by the ASPECTS (Alberta Stroke program early CT score) method and compared amongst each other and with the outcome. ROC (Receiver operating characteristic) curves were plotted considering mRS 0-2 and FIV≤ 28 ml as favourable clinical and radiological outcomes respectively. RESULTS: The study included 55 patients. The 1st and 2nd phase of mCTA-SI correlated significantly with CBF maps (r = 0.845, p < 0.01, r = 0.842, p < 0.01 respectively). 3rd phase of mCTA-SI correlated significantly with CBV maps (r = 0.904, p < 0.01). A favourable functional and radiological outcome was best predicted by the 1st (AUC 0.8, 95%CI 0.671-0.896) and 2nd ( AUC 0.895, 95% CI 0.783-0.962) phase of mCTA-SI respectively. CONCLUSIONS: The 1st and 2nd phases of mCTA-SI produces results congruent to CBF color maps and the 3rd phase of mCTA-SI simulate CBV color maps. In addition to predicting radiological and functional outcomes, mCTA can predict the salvageable and non-salvageable tissue in AIS and is non-inferior to CTP.

Assessment of DHEAS, cortisol, and DHEAS/cortisol ratio in patients with COVID-19: a pilot study.

PURPOSE: Dehydroepiandrosterone sulfate (DHEAS) is observed to be decreased in sepsis and inflammatory conditions. In the present study, we assessed the levels of DHEAS and cortisol and the DHEAS/cortisol ratio and their association with inflammatory markers in patients with COVID-19. METHODS: The study recruited 76 RT-PCR-positive COVID-19-positive patients and 79 healthy controls. The blood samples were collected and were analyzed for cortisol and DHEAS. RESULTS: We observed decreased levels of DHEAS and DHEAS/cortisol ratio and increased levels of cortisol in cases when compared with controls. DHEAS and DHEAS/cortisol ratio showed a decreasing trend with the increase in disease severity. CONCLUSION: The present study is the first of its kind comparing DHEAS levels and DHEAS/cortisol ratio in COVID-19 patients and control subjects. DHEAS, with its inhibitory effect on IL6 and activation of Tregs, may play a crucial role in immune defense mechanisms against COVID-19.

ANN-GA based biosorption of As(III) from water through chemo-tailored and iron impregnated fungal biofilter system.

The iron impregnated fungal bio-filter (IIFB) discs of luffa sponge containing Phanerochaete chrysosporium mycelia have been used for the removal of As(III) from water. Two different forms of same biomass viz. free fungal biomass (FFB) and modified free fungal biomass (chemically modified and iron impregnated; CFB and IIFB) have been simultaneously investigated to compare the performance of immobilization, chemo-tailoring and iron impregnation for remediation of As(III). IIFB showed highest uptake capacity and percentage removal of As(III), 1.32 mg/g and 92.4% respectively among FFB, CFB and IIFB. Further, the application of RSM and ANN-GA based mathematical model showed a substantial increase in removal i.e. 99.2% of As(III) was filtered out from water at optimised conditions i.e. biomass dose 0.72 g/L, pH 7.31, temperature 42 °C, and initial As(III) concentration 1.1 mg/L. Isotherm, kinetic and thermodynamic studies proved that the process followed monolayer sorption pattern in spontaneous and endothermic way through pseudo-second order kinetic pathway. Continuous mode of As(III) removal in IIFB packed bed bioreactor, revealed increased removal of As(III) from 76.40 to 88.23% with increased column height from 5 to 25 cm whereas the removal decreased from 88.23 to 69.45% while increasing flow rate from 1.66 to 8.30 mL/min. Moreover, the IIFB discs was regenerated by using 10% NaOH as eluting agent and evaluated for As(III) removal for four sorption-desorption cycles, showing slight decrease of their efficiency by 1-2%. SEM-EDX, pHzpc, and FTIR analysis, revealed the involvement of hydroxyl and amino surface groups following a non-electrostatic legend exchange sorption mechanism during removal of As(III).

Epithelial-to-mesenchymal transition based diagnostic and prognostic signature markers in non-muscle invasive and muscle invasive bladder cancer patients.

BACKGROUND: Diagnostic and prognostic significance of epithelial-to-mesenchymal transition (EMT) associated biomarkers are evaluated in a cohort of NMIBC (non-muscle invasive bladder cancer) and MIBC (muscle invasive bladder cancer) patients. METHODS AND RESULTS: Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining were carried out in 100 tumor specimens (59 NMIBC and 41 MIBC). The expressions of the epithelial marker, mesenchymal markers and EMT-activating transcription factors (EMT-ATFs) were determined at transcriptome and protein level followed by their statistical associations with clinicohistopathological variables of the patients. Transcriptomic expression analysis showed statistical relevance of tumor stage with increased Twist and Zeb-1; tumor type with reduced E-cadherin and increased Snail; and smoking/tobacco chewing status (S/TC) of patients with increased N-cadherin and Snail in NMIBC patients. Tumor grade with reduced message E-cadherin, gain of N-cadherin, Snail, Twist and Zeb-1; patients' age with reduced E-cadherin and Twist gain; and tumor type with increased message N-cadherin exhibited associations in MIBC patients. Protein expression analysis identified statistical relevance of tumor grade with nuclear gain of Snail and Twist; and nuclear gain of Slug with S/TC status of NMIBC patients. Novel gain of membranous Vimentin deduced association with patients' age in MIBC patients. Survival analysis identified novel Vimentin as the positive predictor of short progression free survival (PFS) and short overall survival (OS) in MIBC patients. Study established altered EMT profile as the independent negative predictor of short recurrence free survival (RFS) in NMIBC patients and positive predictor of short PFS and OS in MIBC patients. CONCLUSIONS: EMT associated biomarkers could provide diagnostic and prognostic risk stratification and hence could be of importance in the clinical management of bladder cancer patients.

Emotional distress among health professionals involved in care of inpatients with COVID-19: a survey based cross-sectional study.

INTRODUCTION: Health care workers (HCWs) are directly involved in processes linked with diagnosis, management, and assistance of coronavirus disease-19 (COVID-19) patients which could have direct implications on their physical and emotional health. Emotional aspects of working in an infectious pandemic situation is often neglected in favour of the more obvious physical ramifications. This single point assessment study aimed to explore the factors related to stress, anxiety and depression among HCWs consequent to working in a pandemic. MATERIAL AND METHODS: This was a cross-sectional study involving healthcare workers who were working in COVID-19 inpatient ward, COVID-19 screening area, suspect ward, suspect intensive care unit (ICU) and COVID-19 ICU across four hospitals in India. A web-based survey questionnaire was designed to elicit responses to daily challenges faced by HCWs. The questionnaire was regressed using machine-learning algorithm (Cat Boost) against the standardized Depression, Anxiety and Stress Scale - 21 (DASS 21) which was used to quantify emotional distress experienced by them. RESULTS: A total of 156 participants were included in this study. As per DASS-21 scoring, severe stress was seen in ∼17% of respondents. We could achieve an R² of 0.28 using our machine-learning model. The major factors responsible for stress were decreased time available for personal needs, increasing age, being posted out of core area of expertise, setting of COVID-19 care, increasing duty hours, increasing duty days, marital status and being a resident physician. CONCLUSIONS: Factors elicited in this study that are associated with stress in HCWs need to be addressed to provide wholesome emotional support to HCWs battling the pandemic. Targeted interventions may result in increased emotional resilience of the health-care system.

Oral Manifestations of COVID-19 Infection: An Analytical Cross-Sectional Study.

Objectives: The current COVID-19 pandemic has created a huge impact across the globe. Recent literature has reported the occurrence of varied oral lesions in COVID-19 patients in the form of sporadic case reports. This analytical cross-sectional study was carried out to gauge and understand the pattern of oral lesions in qualitative RT-PCR-confirmed COVID-19 patients. Methods: A cross-sectional study involves a total of 500 qualitative RT-PCR confirmed, hospitalized COVID-19 patients who were meticulously scanned for any hard and soft tissue lesions developing concomitantly with the disease occurrence. Results: This study included a total of 367 (73.4%) males and 133 (26.6%) female patients with a mean age of 53.46 ± 17.50 years. Almost 51.2% of patients presented with gustatory disturbance, 28% with xerostomia and 15.4% of patients were found to have oral findings like erythema, ulcers, depapillation of tongue. There was a statistically significant correlation between oral manifestations and disease severity (p ≤ 0.001). Conclusion: COVID-19 is found to effect oral health with greater probability in patients with severe diseases (SARI) which may be due to disease itself, immune response and lack of motivation for personal hygiene measures. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-021-01679-x.

Phosphoproteome of signaling by ErbB2 in ovarian cancer cells.

The gene for receptor tyrosine kinase ErbB2 is amplified in breast and ovarian tumours. The linear pathway by which signals are transduced through ErbB2 are well known. However, second generation questions that address spatial aspects of signaling remain. To address this, we have undertaken a mass spectrometry approach to identify phosphoproteins specific for ErbB2 using the inhibitors Lapatinib and CP724714 in ovarian cancer cells. The ErbB2 specific proteins identified in SKOV-3 cells were Myristoylated alanine-rich C-kinase substrate, Protein capicua homolog, Protein peptidyl isomerase G, Protein PRRC2C, Chromobox homolog1 and PRP4 homolog. We have evaluated three phosphoproteins PKM2, Aldose reductase and MARCKS in SKOV-3 cells. We observed that PKM2 was phosphorylated by EGF but was not inhibited by Lapatinib and CP724714. The activity of aldose reductase in reducing NADPH as a substrate was significantly higher in EGF stimulated cells which was inhibited by Lapatinib and CP724714 but not by Geftinib (EGFR inhibitor). MARCKS was phosphorylated on stimulation of SKOV-3 cells with EGF that was inhibited by Lapatinib and CP724714 which was dependent on the kinase activity of ErbB2. These results have identified phosphoproteins that are specific to ErbB2 which have not been previously reported and sets the basis for future experiments.