Increased tracheostomy rates in head and neck cancer surgery during the COVID-19 pandemic.

Surgical practice during the coronavirus disease 2019 (COVID-19) pandemic has changed significantly, without supporting data. With increasing experience, a dichotomy of practice is emerging, challenging existing consensus guidelines. One such practice is elective tracheostomy. Here, we share our initial experience of head and neck cancer surgery in a COVID-19 tertiary care centre, emphasizing the evolved protocol of perioperative care when compared to pre-COVID-19 times. This was a prospective study of 21 patients with head and neck cancers undergoing surgery during the COVID-19 pandemic, compared to 193 historical controls. Changes in anaesthesia, surgery, and operating room practices were evaluated. A strict protocol was followed. One patient tested positive for COVID-19 preoperatively. There was a significant increase in pre-induction tracheostomies (28.6% vs 6.7%, P=0.005), median hospital stay (10 vs 7 days, P=0.001), and postponements of surgery (57.1% vs 27.5%, P=0.01), along with a significant decrease in flap reconstructions (33.3% vs 59.6%, P=0.03). There was no mortality and no difference in postoperative morbidity. No healthcare personnel became symptomatic for COVID-19 during this period. Tracheostomy is safe during the COVID-19 pandemic and rates have increased. Despite increased rescheduling of surgeries and longer hospital stays, definitive cancer care surgery has not been deferred and maximum patient and healthcare worker safety has been ensured.

Rhabdomyosarcoma of the cervix in teenagers - Is fertility preservation a feasible option?

Embryonal rhabdomyosarcoma (RMS) of the cervix is a rare entity, encountered mainly in the first two decades of life. The literature consists mainly of case reports and few small case series, and no standard treatment guidelines are available. As this is a disease of adolescence, fertility preservation in well selected cases is of paramount importance. We report 3 cases of cervical RMS, in adolescents highlighting the clinical presentation, diagnosis and management.

Quality of life outcomes one year after replacement of the temporomandibular joint using a modified SF36 questionnaire.

The aim of this study was to assess the quality of life (QoL) of patients who had total replacement of the temporomandibular joint (TMJ) using a modified short form 36 (SF36) questionnaire, which is validated for use in this context. A total of 36 patients (32 female, 4 male, mean (range) age at the time of operation 44.5 (19-74) years) who had TMJ replacements between 2013 and 2016 were evaluated. Each completed a questionnaire preoperatively and at one year postoperatively. Postoperatively there were significant reductions in scores for pain and anxiety, and improvements in mood, diet, and the ability to chew. There were no significant differences between the preoperative and postoperative scores in terms of speech or recreation, although most reported an overall improvement in general well-being. Our results suggest that TMJ replacement is associated with a better QoL in terms of pain and function, and that the modified questionnaire is suitable for the appraisal of outcomes after this type of operation.

Analysis of outcomes after revision replacement of failed total temporomandibular joint prostheses.

End-stage disease of the temporomandibular joint (TMJ) can be managed successfully with alloplastic total replacements, but these can fail because of allergy, infection, wear, fracture, and heterotopic development of bone. We prospectively reviewed the outcome data of all patients who required revision of previously placed replacement joints between 2004 and 2016. Data included pain and diet scores using 100mm visual analogue scales (VAS), and interincisal distance recorded before, and at six weeks, six months and 12 months after operation. The reasons for failure and the number of previous procedures were also noted. Twenty patients (26 joints) had revisions. The reasons included infection (n=9), reankylosis (n=5), wear of the existing prosthesis (n=2), fracture of the prosthesis (n=2), foreign body reaction (n=1), and allergy to the prosthesis (n=1). The mean (range) age of the patients was 53.3 (47-68) years, and 15 were female and five male. Preoperatively, the mean (SD) pain score was 73.1 (22.4), mouth opening was 20.9 (10.2) mm, and diet score 41.7 (23.6). At 12-month follow up, all the measurements had improved significantly (p≤0.05), with the pain score improving to a mean (SD) of 18.4 (25.2), mouth opening to 32.2 (9.3) mm, and diet score to 89.4 (18.5). Revision replacements done by an experienced team result in considerably improved outcomes with limited complications, but the improvements in function and pain are not as marked as they are after primary replacement.

Hemophagocytic lymphohistiocytosis presenting with acute liver failure and central nervous system involvement in early infancy.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal and likely underdiagnosed disease characterized by unregulated histiocyte proliferation, hypercytokinemia and hemophagocytosis, causing life-threatening tissue damage and organ failure. We report a case of a 56-day-old infant presenting with fever, acute liver failure, and neurological manifestations as presenting features that succumbed to rapidly progressive HLH. Our objective is to emphasize the importance of early diagnosis by high suspicion in varied initial presentation of HLH so that life-saving therapy may be instituted in time.

Early Detection of Right Ventricular Dysfunction in Chronic Obstructive Pulmonary Disease by Echocardiography.

OBJECTIVE: This study is designed to investigate the effects of pulmonary arterial hypertension on RV systolic and diastolic functions in cases of COPD and to correlate RV systolic and diastolic functions with pulmonary arterial pressure. MATERIALS AND METHODS: 100 patients admitted in various medical wards of tertiary care Hospital and a primary care hospital with stable chronic obstructive pulmonary disease persons with age and sex-matched. 35 age and sex matched person without any associated and known disease were taken as control subjects. Selection of cases has been made on basis of detailed history, thorough clinical examination, electrocardiography, chest x-ray, pulmonary function tests. OBSERVATION: RV Systolic function (RVEF and RVWT) are significantly abnormal in patients of stable compensated COPD and they are significantly correlated with PAP(p< 0.002). RV diastolic function i.e., E/A ratio and PFR are altered in 60%(n-60) of patients of COPD studied against control subjects and significantly correlated with PAP(p< 0.002). CONCLUSION: Echocardiography is a non invasive method to detect changes of right ventricular dysfunctions in early stages with very good significant sensitivity and specificity.

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity.

BACKGROUND: LGR5 serves as a co-receptor for Wnt/ß-catenin signalling and marks normal intestinal stem cells; however, its role in colorectal cancer (CRC) remains controversial. LGR5+ cells are known to exist outside the stem cell niche during CRC progression, and the requirement for epidermal growth factor (EGF) signalling within early adenomas remains to be fully elucidated. METHODS: Epidermal growth factor and gefitinib treatments were performed in EGF-responsive LGR5+ early adenoma RG/C2 cells. 2D growth assays were measured using an IncuCyte. LGR5 or MEK1/2 silencing studies were executed using siRNA and LGR5 expression was assessed by qRT-PCR and immunoblotting. Ki67 level and cell cycle status were analysed by flow cytometry. RESULTS: Epidermal growth factor suppresses expression of LGR5 at both the transcript and protein level in colorectal adenoma and carcinoma cells. Suppression of LGR5 reduces the survival of EGF-treated adenoma cells by increasing detached cell yield but also inducing a proliferative state, as evidenced by elevated Ki67 level and enhanced cell cycle progression. Repression of LGR5 further increases the sensitivity of adenoma cells to EGFR inhibition. CONCLUSIONS: LGR5 has an important role in the EGF-mediated survival and proliferation of early adenoma cells and could have clinical utility in predicting response of CRC patients to EGFR therapy.

Transfer of CVD-grown graphene for room temperature gas sensors.

An easy transfer procedure to obtain graphene-based gas sensing devices operating at room temperature (RT) is presented. Starting from chemical vapor deposition-grown graphene on copper foil, we obtained single layer graphene which could be transferred onto arbitrary substrates. In particular, we placed single layer graphene on top of a SiO2/Si substrate with pre-patterned Pt electrodes to realize a chemiresistor gas sensor able to operate at RT. The responses to ammonia (10, 20, 30 ppm) and nitrogen dioxide (1, 2, 3 ppm) are shown at different values of relative humidity, in dark and under 254 nm UV light. In order to check the sensor selectivity, gas response has also been tested towards hydrogen, ethanol, acetone and carbon oxide. Finally, a model based on linear dispersion relation characteristic of graphene, which take into account humidity and UV light effects, has been proposed.

Evaluation of serum galactomannan enzyme immunoassay at two different cut-offs for the diagnosis of invasive aspergillosis in patients with febrile neutropenia.

BACKGROUND: Invasive aspergillosis (IA) is an increasingly common and fatal opportunistic fungal infection in patients with haematological diseases. Early diagnosis is difficult as mycological culture techniques have low sensitivity and the radiological tools have low specificity. Galactomannan enzyme immunoassay (GEI) detects galactomannan in the human serum with a reported sensitivity and specificity between 30% and 100%. AIMS: The aim of this study was to analyse the role of GEI in diagnosis of IA in patients with febrile neutropenia and to evaluate the role of GEI in the diagnosis of IA as per the revised (2008) European Organization for Research and Treatment of Cancer-Mycoses Study Group (EORTC-MSG) criteria at two different optical density (OD) cut-offs of 0.5 and 1.0. SETTING: This prospective study was conducted in Safdarjung Hospital, New Delhi, India. METHODS: GEI testing was performed in adult patients of febrile neutropenia with evidence of IA. Results at two different OD indices (ODIs) of 0.5 and 1.0 were analysed. The evaluation of the diagnostic parameter, that is, GEI was measured in terms of sensitivity, specificity and positive and negative predictive value and was validated with the revised (2008) EORTC-MSG diagnostic criteria of IA. RESULTS: One hundred and eleven patients had evidence of IA, of which 79 patients were GEI positive when cut-off ODI was 0.5, whereas with cut-off ODI 1.0, 55 patients were GEI positive. CONCLUSION: ODI of 1.0 should be considered as positive while in patients with OD between 0.5 and 1.0, repeat sampling from the patient is recommended.

Characterization of cancer stem cells from different grades of human colorectal cancer.

Colorectal cancer (CRC) is one of the most common solid tumors worldwide. Recent evidence suggests that a population of cancer cells, called cancer stem cells (CSCs), is responsible for tumor heterogeneity, invasion, metastasis, therapeutic resistance, and recurrence of CRC. The isolation and characterization of CSCs using cell surface markers have been reported previously with varying results. In this study, we investigated a panel of four putative CSC markers, CD44, CD24, CD166, and EpCAM, to define CRC-CSC. Paraffin embedded tissue samples from different grades of primary, untreated CRC were analyzed for the expression of four CSC markers CD44, CD326, CD24, and CD166, using immunohistochemistry. Flow cytometric analysis of CRC-CSC from HT29 (low grade) and HCT116 (high grade) human colorectal cancer cell lines was done. Marker-based isolation of CSC and non-CSC-bulk-tumor cells from HT29 was done using FACS, and tumor sphere assay was performed. There was a statistically significant difference (p < 0.05) in the expression of CD44, CD326, and CD166 between cases and controls. A novel cutoff distribution of CD44 and CD166 was suggested to help for better immunohistochemical analysis of CRC. Higher prevalence of CSC was seen in high-grade CRC as compared to low-grade CRC. Sorted and cultured CD44 + CD166+ cells formed tumor spheres, suggesting that these cells, having properties of self renewal and anchorage independent proliferation, were in fact CSC. Hence, CD44 and CD166 may serve as good CRC-CSC markers when used together with novel cutoff immunohistochemistry (IHC) expression levels.

CSF ADA Determination in Early Diagnosis of Tuberculous Meningitis in HIV-Infected Patients.

Tuberculous and Cryptococcal meningitis are common in HIV patients. A highly specific and sensitive rapid test for diagnosis of Tuberculous meningitis especially in setting of HIV is not available in developing countries where the burden of disease is high. We measured ADA (adenosine deaminase) levels using spectrophotometric method in the CSF of HIV patients with meningitis to differentiate Tuberculous meningitis from meningitis due to other causes. Kruskal-Wallis test was used to compare ADA values between tuberculous meningitis (TBM) and nontuberculous (non-TB) meningitis patients and a receiver-operating characteristic (ROC) analysis curve was drawn from these values. Levels of ADA in the CSF of patients with TBM were significantly higher than those in patients with meningitis due to other causes. CSF ADA level determination with a cut-off value of 6 IU/L was found to be highly specific and fairly sensitive test for the diagnosis of TBM in HIV positive patients.

Evaluation of Aspartate Aminotransferase-to-Platelet Ratio Index as a Non-Invasive Marker for Liver Cirrhosis.

INTRODUCTION: Liver biopsy is considered as a gold standard for the diagnosis of cirrhosis. Till date there is no non-invasive marker to replace it. AIM: To investigate the effectiveness of Aspartate aminotransferase-to-platelet ratio index (APRI) as a non-invasive marker for liver cirrhosis. MATERIALS AND METHODS: Fifty-one patients with cirrhosis, identified on USG abdomen were included in study. Platelet count and Aspartate aminotransferase (AST) were done using haematology automatic analyser and automatic HITACHI-912 Auto Analyser respectively. APRI was calculated for every patient using the formula {(AST / ULN) x 100}/platelet count (10(9)/L). Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. RESULTS: APRI correctly classified 49 (96.1%) patients of cirrhosis with area under the ROC curve of 0.973 (95% CI) at cut-off 0.65 with negative predictive value (NPV) and Positive predictive value (PPV) of 96% and 96.1% respectively. The sensitivity and specificity of the test was found to be 96% and 96.1% respectively. CONCLUSION: APRI could identify cirrhosis with high degree of accuracy in the studied patients.

Nanobiocomposite from Collagen Waste Using Iron Oxide Nanoparticles and Its Conversion Into Magnetic Nanocarbon.

Collagenous wastes discarded from leather industry were stabilized using superparamagnetic iron oxide nanoparticles and further converted into a magnetic nanocarbon. Stabilization of collagen using iron oxide nanoparticles treatment (25% offer) was confirmed through differential scanning calorimetric analysis and further evidenced through scanning electron microscopic analysis. A simple high temperature treatment of the collagen-iron oxide nanoparticle composite at 850 degrees C for 2 h under Ar atmosphere yielded a bi-functional, magnetic and conducting, nanocarbon. The X-ray diffraction and Raman spectroscopic analysis reveal the partial graphitation and X-ray photoelectron spectroscopic results show the presence of trace-iron containing carbon, naturally doped with nitrogen and oxygen. Transmission electron microscopic analysis show the presence of larger iron oxide nanocrystals embedded in graphitic carbon layers while superconducting quantum interference device based analysis reveals a perfect ferrimagnetic property with saturation magnetization. Thus, we have stabilized the collagen waste fibers using iron oxide nanoparticles and converted them into a bi-functional nanocarbon, which has potential for various applications including energy, leather making and environmental remediation.

Role of fine-needle aspiration cytology in human immunodeficiency virus-associated lymphadenopathy: a cross-sectional study from northern India.

OBJECTIVE: To evaluate the role of fine-needle aspiration cytology in the diagnosis of human immunodeficiency virus (HIV)-associated lymphadenopathy. DESIGN: Case series. SETTING: Tertiary care teaching hospital, India. PATIENTS: Fifty consecutive HIV-positive patients, who presented with lymphadenopathy at the out-patient department and antiretroviral therapy clinic. RESULTS: Tubercular lymphadenitis was the most common diagnosis, reported in 74% (n=37) of patients; 97.2% of them were acid-fast bacilli-positive. Reactive lymphadenitis and fungal lymphadenitis were present in 10 and 1 cases, respectively. The most common cytomorphological pattern of tubercular lymphadenitis was necrotising suppurative lymphadenitis, present in 43.2% (n=16) of patients. Of eight biopsies done in reactive cases, six turned out to be tubercular lymphadenitis. Fine-needle aspiration cytology had a sensitivity of 83.7% for diagnosing tubercular lymphadenitis. CONCLUSION: Necrotising suppurative lymphadenitis should be recognised as an established pattern of tubercular lymphadenitis. Reactive patterns should be considered inconclusive rather than a negative result, and re-evaluated with lymph node biopsy. Fine-needle aspiration cytology is an excellent test for diagnosing tubercular lymphadenitis in HIV-associated lymphadenopathy.

Clinical & biochemical profile of trichinellosis outbreak in north India.

BACKGROUND & OBJECTIVES: Trichinellosis is a parasitic infection caused by Trichinella nematodes, acquired from consumption of raw meat. However, data from Indian subcontinent are limited. The aim of this study was to investigate the clinical and biochemical profile of a suspected trichinellosis outbreak in a village in Tehri Garhwal district of Uttarakhand state in north India. METHODS: Three index cases presenting as acute febrile myalgia syndrome with eosinophilia, after consumption of uncooked pork in a common feast, were confirmed as trichinellosis on muscle biopsy. A detailed epidemiological survey was carried out in the affected community and all the people who participated in the feast were investigated for clinical and biochemical profile. RESULTS: A total of 54 patients were evaluated in the study. The type of pork consumed included uncooked in 24 per cent (n=13), open fire roasted in 39 per cent (n=21) and fried in 37 per cent (n=20). Clinical symptoms were found in those who consumed pork in uncooked or open fire roasted form (n=34). These included fever with chills and myalgia (100%), periorbital oedema (67%), dyspnoea (9%), and dysphagia (3%). Laboratory parameters studied in both symptomatic and asymptomatic patients showed eosinophilia in 90 per cent (n=41), raised ESR in 98 per cent (n=45), and an elevated creatinine phosphokinase (CPK) level in 85 per cent (n=39). All symptomatic patients were treated with a short course of oral steroids and albendazole therapy. CONCLUSIONS: Trichinella infection is not uncommon in India, and should be suspected in case of acute febrile myalgia especially in areas, where habits of consumption of raw meat is more prevalent.

Incremental (?) role of positron emission tomography/computed tomography in clinically unknown primary patients with neck metastasis.

OBJECTIVE: To study the incremental role of positron emission tomography (PET)/computed tomography (CT) in the detection of primary site in cases of occult primary with neck metastasis. STUDY DESIGN: A prospective study on 79 consecutive patients. SETTING: A tertiary care otolaryngology and head and neck surgery center. MATERIALS AND METHODS: This prospective study compares the results of PET/CT in 79 patients of occult primary with neck metastasis with that of detailed comprehensive head and neck examination including imaging and panendoscopy. This study also attempts to define the incremental role of PET/CT in patients of occult primary. RESULTS: The sensitivity of PET/CT in identifying the primary tumor was 62.4%, the specificity was 64.7%, the positive predictive value was 69.7% and the negative predictive value was 93%. We had a false positive rate of 33.6% and a false negative rate of 2.6%. CONCLUSION: PET/CT is a sensitive investigation for detection of occult primary. However, it has a low specificity rate and a high false positivity rate. Due to a high false positive rate, multiple biopsies from suspicious sites should be taken rather than solely relying on PET/CT. PET/CT guided fine needle aspiration cytology should be utilized more frequently than we did in this study.

Ubiquitin-like (UBX)-domain-containing protein, UBXN2A, promotes cell death by interfering with the p53-Mortalin interactions in colon cancer cells.

Mortalin (mot-2) induces inactivation of the tumor suppressor p53's transcriptional and apoptotic functions by cytoplasmic sequestration of p53 in select cancers. The mot-2-dependent cytoprotective function enables cancer cells to support malignant transformation. Abrogating the p53-mot-2 interaction can control or slow down the growth of cancer cells. In this study, we report the discovery of a ubiquitin-like (UBX)-domain-containing protein, UBXN2A, which binds to mot-2 and consequently inhibits the binding between mot-2 and p53. Genetic analysis showed that UBXN2A binds to mot-2's substrate binding domain, and it partly overlaps p53's binding site indicating UBXN2A and p53 likely bind to mot-2 competitively. By binding to mot-2, UBXN2A releases p53 from cytosolic sequestration, rescuing the tumor suppressor functions of p53. Biochemical analysis and functional assays showed that the overexpression of UBXN2A and the functional consequences of unsequestered p53 trigger p53-dependent apoptosis. Cells expressing shRNA against UBXN2A showed the opposite effect of that seen with UBXN2A overexpression. The expression of UBXN2A and its apoptotic effects were not observed in normal colonic epithelial cells and p53-/- colon cancer cells. Finally, significant reduction in tumor volume in a xenograft mouse model in response to UBXN2A expression was verified in vivo. Our results introduce UBXN2A as a home defense response protein, which can reconstitute inactive p53-dependent apoptotic pathways. Inhibition of mot-2-p53 interaction by UBXN2A is an attractive therapeutic strategy in mot-2-elevated tumors.

Synthesis and anticancer activity of novel spiro-isoxazoline and spiro-isoxazolidine derivatives of α-santonin.

In the present study, novel spiro derivatives of α-santonin were prepared and tested for their anticancer activity against a panel of six human cancer cell lines. Spiro-isoxazoline and spiro-isoxazolidine derivatives have been generated on C-ring of α-santonin (α-methylene-γ-butyrolactone) by the 1,3-dipolar cycloaddition of α-santonin derivative 6 with nitrile oxides 7 and nitrones 9 respectively. Among all, compound 10b″ had shown IC50 of 0.01, 0.5 and 0.3 µM against PC-3, THP-1 and MCF-7 cell lines respectively. Further, flow cytometry studies showed that PC-3 cells treated with the spiro-isoxazolidine derivative 10b″ were arrested in the sub G1 phase of the cell cycle in a concentration dependent manner. The spiro-isoxazolidine derivative 10b″ also showed concentration dependent inhibitory activity against NF-κB, p65 with 57% inhibition in 24 h at 10 µM.