Treatment prioritization and risk stratification of head and neck cancer during COVID-19 pandemic: A systematic review.

INTRODUCTION: Treatment of head and neck cancer patients amidst the COVID-19 pandemic is challenging, whereas prolonged treatment initiation in head and neck squamous cell carcinoma may increase mortality and likelihood of recurrence. Special attention is needed to ensure safe and appropriate care of these patients. This article aims to review and discuss existing research on treatment prioritization and risk stratification of head and neck cancer patients during the pandemic. MATERIALS AND METHODS: The authors conducted literature search in three databases (PubMed, Cochrane, and Clinical Key) on July 15th, 2020. The keywords were ("Head and Neck Mucosal Malignancy" OR "Head and Neck Cancer") AND ("Management" OR "Head and Neck Surgery") AND ("COVID-19" OR "Pandemic"). The inclusion criteria were cancer in adult patients, published from 2020 in English, and with available access to full text. The exclusion criteria were comments, letters, and case reports. The articles were critically appraised using the Centre of Evidence-based Medicine (CEBM), University of Oxford and Duke University. The literature search strategy is illustrated using Preferred Reporting Items for Systematic review and meta-analysis (PRISMA) flow diagram. RESULTS: A total of 150 articles were identified; 21 articles were gathered from Clinical Key, 33 from Cochrane, and 96 from Pubmed. After screening abstracts and reviewing the full text, the authors determined five articles met the inclusion criteria. There are several key points of head and neck cancer management in the COVID-19 pandemic. Head and neck cancer management is considered a high-risk procedure; the clinician should use proper personal protective equipment. Before operative treatment, all patients should undergo a PCR test 14 days before surgery. In diagnosing head and neck cancer, laryngoscopy should be considered carefully; and cytology should be preferred instead. Medically Necessary, Time-sensitive (MeNTS) score is recommended for risk stratification and surgery prioritization; it has three domains: procedure, disease, and patient. However, it is not specified to head and neck cancer; therefore, it should be combined with other references. Stanford University Head and Neck Surgery Division Department of Otolaryngology made surgery prioritization into three groups, urgent (should be operated immediately), can be postponed for 30 days, and can be postponed for 30- 90 days. Some urgent cases and should be operated on immediately include cancers involving the airways, decreased renal function, and metastases. For chemoradiation decision to delay or continue should refer to the goal of treatment, current oncologic status, and tolerance to radiation. In terms of patient's follow up, telephone consultation should be maximized. CONCLUSION: MeNTS scoring combined with Guideline from Department of Otolaryngology at Stanford University prioritizing criteria can be helpful in decision making of stratifying Risk and prioritizing surgery in head and neck cancer management.

The effects of Goldenhar Syndrome on hearing and speech development.

Goldenhar syndrome is a congenital abnormality with an incidence of 1 in 5,200 to 26,500 births. This syndrome is characterized by facial asymmetry, ear malformation, and/or defects in the eyes and vertebrae. The hearing disorder manifests as both conductive or sensorineural due to the abnormalities occurring in the inner and outer ear. We report a case of a 1-year-3-month-old child presenting with left anotia and right microtia, severe bilateral conductive hearing loss, and global delayed development. The patient was also found to have a hemifacial microsomia, a secundum atrial septal defect (ASD), and a ventricular septal defect (VSD). The patient was advised to use hearing aids and participate in speech therapy. The management of this Goldenhar syndrome patient should be done comprehensively, appropriate to the abnormalities found to achieve the best result.

The influence of social stress on time perception and psychophysiological reactivity.

Time perception is a fundamental component of everyday life. Although time can be measured using standard units, the relationship between an individual's experience of perceived time and a standard unit is highly sensitive to context. Stressful and threatening stimuli have been previously shown to produce time distortion effects, such that individuals perceive the stimuli as lasting for different amounts of time as compared to a standard unit. As a highly social species, humans are acutely sensitive to social stressors; however, time distortion effects have not been studied in the context of social stress. We collected psychophysiological (electrocardiogram and impedance cardiography) and time perception data before, during, and after a modified version of the Trier Social Stress Test for 42 participants. Based on prior theories and evidence from the time perception literature, we hypothesized that experiencing a stressful event would result in time distortion. This hypothesis was supported by the data, with individuals on average reproducing short and long duration negative and positive stimuli as lasting longer after experiencing social stress, t(41) = -3.55, p = .001, and t(41) = -4.12, p < .001 for negative stimuli, and t(41) = -2.43, p = .02, and t(41) = -3.07, p = .004 for positive stimuli. However, changes in time perception were largely unrelated to psychophysiological reactivity to social stress. These findings are in line with some other studies of time distortion, and provide evidence for the interoceptive salience model of time perception. Implications for mechanisms of time distortion are discussed.

Amnion-derived multipotent progenitor cells support allograft tolerance induction.

Donor-specific immunological tolerance using high doses of bone marrow cells (BMCs) has been demonstrated in mixed chimerism-based tolerance induction protocols; however, the development of graft versus host disease remains a risk. Here, we demonstrate that the co-infusion of limited numbers of donor unfractionated BMCs with human amnion-derived multipotent progenitor cells (AMPs) 7 days post-allograft transplantation facilitates macrochimerism induction and graft tolerance in a mouse skin transplantation model. AMPs + BMCs co-infusion with minimal conditioning led to stable, mixed, multilineage lymphoid and myeloid macrochimerism, deletion of donor-reactive T cells, expansion of CD4(+)CD25(+)Foxp3(+) regulatory T cells (T(regs)) and long-term allograft survival (>300 days). Based on these findings, we speculate that AMPs maybe a pro-tolerogenic cellular therapeutic that could have clinical efficacy for both solid organ and hematopoietic stem cell transplant applications.

Pattern of congenital heart diseases.

This prospective observational study was done to find out the frequency of various forms of congenital heart disease (CHD) diagnosed by echocardiography. During the study period (January 2002 to December 2005) 2050 patients were screened by echocardiography. All patients were evaluated by cardiologists and had chest radiograph, electrocardiogram and echocardiography. Total 2050 patients were studied and among them 1071 had congenital heart disease. Male was 561(52.38%) and female was 510(47.62%). Atrial septal defect (ASD) was 374(34.92%), ventricular septal defect (VSD) was 318(29.69%), patent ductus arteriosus (PDA) 83(7.75%), pulmonary stenosis (PS) 58(5.42%), tetralogy of Fallot 162(15.13%), transposition of great vessels (TGA) 16(1.49%), Ebstein anomaly 5(0.4%), coarctation of aorta 1(0.09%) and single ventricle 2(0.19%). This distribution is more or less similar to that reported in studies at home and abroad. In this study atrial septal defect (ASD) was the commonest in acyanotic CHD and tetralogy of Fallot was the commonest cyanotic CHD.

Clinical and angiographic profile of congenital anomalous origin of coronary arteries.

Coronary artery anomalies were found in 24(0.6%) patients undergoing coronary arteriography at University Cardiac Center, Bangabandhu Sheikh Mujib Medical University, Dhaka from 2004 to 2007. Of the 24 patient, 21(87.5%) had anomalies of origin and distribution and 3(12.5%) had coronary artery fistulae. Most coronary anomalies did not result in signs, symptoms or complications and usually were discovered as an incidental finding at the time of catheterization. Most of them were benign anomalies: i) separate origin of left anterior descending and circumflex from sinus of valsalva; ii) ectopic origin of circumflex from right sinus of valsalva; iii) Anomalous origin of left main coronary artery from right coronary artery; iv) anomalous coronary origin from ascending aorta; v) absent left circumflex; vi) double right coronary artery; vii) small coronary artery fistula. These anomalies may be associated with potentially serious sequelae such as angina pectoris, myocardial infarction, syncope, cardiac arrhythmias, congestive heart failure, or sudden death. In this study large coronary artery fistula was found as potentially serious anomaly. So coronary artery anomalies require accurate recognition for the appropriate management of the patients.

Outcome of pregnancy in patients with congenital heart diseases.

This prospective study was conducted to evaluate the outcome of pregnancies in women with congenital heart diseases. In this study 50 pregnant women age between 20-45 years with congenital heart diseases were included. Twenty two (44%) were presented with atrial septal defect, 12(24%) with ventricular septal defect, 5(10%) were with patent ductus arteriosus, 6(12%) with Fallot's tetralogy, 2(4%) with pulmonary stenosis, 2(4%) with Eisenmenger syndrome, 1(2%) with dextrocardia. Shortness of breath (60%) was the main presenting complaint. Normal vaginal delivery (52%) was done in majority of cases. Spontaneous abortion occurred in 16% of pregnancies. Major complications were heart failure 16%, arrhythmias 21%, cardiovascular mortality 4%, preeclampsia 4%, and eclampsia 2%. Premature birth 16%, fetal demise 4%, neonatal death 2% and cardiac anomaly at birth 2% were also observed. The outcome of pregnancy in women with congenital heart diseases is favourable with considerable maternal and neonatal complications.

Valvular heart disease in pregnancy: maternal and fetal outcome.

The aim of this study was to evaluate the maternal and fetal outcome of pregnancy in Valvular Heart Disease (VHD). A better understanding of the effects of valvular abnormalities on pregnancy outcome is of value for risk assessment and the design of a therapeutic plan from the available information of a series of patient. A multicenter prospective study was carried out over a period of 5 years (2005-2009) involving 60 pregnant patients with valvular heart disease. Thirty eight patients (64%) had single valve involvement and mitral stenosis was the most predominant lesion (50%). Ten patients (16.7%) had undergone interventional and surgical correction prior to the pregnancy. Fourteen (24%) patients were identified as a NYHA class III-IV. Women with VHD had 8.35% pulmonary edema, 15.03% developed different types arrhythmia. The incidence of preterm birth and small for gestational age newborn was 11.69% and 13.36% respectively. There was one (1.67%) maternal death. Pregnancy in women with valvular heart disease is associated with remarkable unfavourable effect on maternal and fetal outcome which are related to severity of disease.

Balloon mitral valvuloplasty: immediate and short term haemodynamic and clinical outcome.

This prospective study was carried out in the Department of Cardiology, University Cardiac Center, Banghabandhu Sheikh Mujib Medical University, Dhaka, to evaluate the short term clinical and haemodynamic outcome of Balloon mitral valvuloplasty in mitral stenosis. Total 100 patients underwent percutaneous mitral commissurotomy out of which 60 cases had pure mitral stenosis and 40 patients had concomitant other nonsignificant valvular disease. Mitral valve dilatation increases in mitral valve area from 0.5+/-0.22 to 1.80+/-0.41 cm2. Mitral valve mean pressure gradient decline from 24.0+/-6.48 mm of Hg to 6.1+/-3.0 mm of Hg: mean left arterial pressure decline from 21.40+/-4.80 mm of Hg to 6.50+/-2.82 mm of Hg (p<0.001). The pulmonary artery systolic pressure decreased from 78.7+/-20.34 mm of Hg to 30.18+/-10.8 mm of Hg (p<0.001). Procedural success, as defined final mitral valve area>1.5 cm2 or>50% increase in area, was achieved in 95% patients. Serious complications occurred in 2(2%) patients and no death occurred in the study. Minor complications such as vasovagal reaction (03%), balloon rupture without sequelae (1%), hypotension, Seizure etc. during the procedure were also noted. Although percutaneous transvenous mistral commissurotomy appears to be effective at relieving the hemodynamic effects of rheumatic mitral stenosis, it is not without risk. In properly selected patients, however, it appears to have low morbidity and mortality. The overall results of this study demonstrate that the short term clinical and haemodynamic outcome of the procedure were excellent and the incidence of related complications were reasonable.

Severe tissue trauma triggers the autoimmune state systemic lupus erythematosus in the MRL/++ lupus-prone mouse.

Tissue damage associated with a severe injury can result in profound inflammatory responses that may trigger autoimmune development in lupus-prone individuals. In this study, we investigated the role of a large full-thickness cutaneous burn injury on the early onset of autoimmune disease in lupus-prone MRL/++ mice. MRL/++ mice (chronic model) exhibit autoimmune symptoms at >70 weeks of age, whereas MRL/-Fas(lpr) mice (acute model) develop autoimmune disease in 17-22 weeks due to a lymphoproliferative mutation. Autoimmune disease developed in MRL/++ mice (4-15 weeks post injury) is manifested by skin lesions, vasculitis, epidermal ulcers, cellular infiltration, splenomegaly, lymphadenopathy, hypergammaglobulinemia, elevated autoantibodies and renal pathologies including proteinuria, glomerulonephritis and immune complex deposition; complications that contribute to reduced survival. Transcription studies of wound margin tissue show a correlation between the pathogenic effects of dysregulated IL-1beta, IL-6, TNF-alpha and PGE(2) synthesis during early wound healing and early onset of autoimmune disease. Interestingly, MRL/++ mice with healed wounds (30-40 days post burn) strongly rejected skin isografts. Conversely, skin isografts transplanted onto naive age-matched MRL/++ littermates achieved long-term survival. Collectively, these findings suggest that traumatic injury exacerbates inflammatory skin disease and severe multi-organ pathogenesis in lupus-prone mice.

Influence of phospholipid composition on the adjuvanticity and protective efficacy of liposome-encapsulated Leishmania donovani antigens.

In this study, we evaluate the effect of phospholipid on the adjuvanicity and protective efficacy of liposome vaccine carriers against visceral leishmaniasis (VL) in a hamster model. Liposomes prepared with distearyol derivative of L-alpha-phosphatidyl choline (DSPC) having liquid crystalline transition temperature (Tc) 54 C were as efficient as dipalmitoyl (DPPC) (Tc 41 C) and dimyristoyl (DMPC) (Tc 23 C) derivatives in their ability to entrap Leishmania donovani membrane antigens (LAg) and to potentiate strong antigen-specific antibody responses. However, whereas LAg in DPPC and DMPC liposomes stimulated inconsistent delayed type hypersensitivity (DTH) responses, strong DTH was observed with LAg in DSPC liposomes. The heightened adjuvant activity of DSPC liposomes corresponded with 95% protection, with almost no protectivity with LAg in DPPC and DMPC liposomes, 4 mo after challenge with L. donovani. These data demonstrate the superiority of DSPC liposomes for formulation of L. donovani vaccine. In addition, they demonstrate a correlation of humoral and cell-mediated immunity with protection against VL in hamsters.

Leishmanicidal activity of stearylamine-bearing liposomes in vitro.

Liposomes consisting of stearylamine (SA) and egg yolk phosphatidylcholine (PC) were studied for their cytotoxic activity against freshly transformed promastigotes and intracellular amastigotes of Leishmania donovani, the causative agent of visceral leishmaniasis. More than 99% of the parasites of strain AG83 were killed within 60 min by treatment with 22 mol% SA-PC liposomes (132 microg/ml total lipids). This was further confirmed by incubating the liposome-treated promastigotes at 22 C for 96 hr. The killing activity of the liposomes progressively decreased with lowering lipid concentration. However, weak cytotoxic activity was still detected at 6.6 microg/ml lipids. Leishmanicidal activity of the liposomes became stronger with increasing SA content but was reduced with the incorporation of cholesterol in the liposomes. A similar cytotoxic effect was observed on other Indian strains of L. donovani, for example PKDL and DD8, as well as on species such as Leishmania donovani S1, Leishmania donovani infantum, Leishmania tropica, Leishmania amazonensis, and Leishmania mexicana. However, freshly transformed promastigotes appeared to be more susceptible than the ones subcultured. The strong leishmanicidal activity of SA-PC liposomes was also demonstrated toward intracellular L. donovani amastigotes. The SA-bearing vesicles could effectively inhibit the growth and multiplication of the parasites within the macrophages. The cytolytic activity of these liposomes on leishmanial parasites and low toxicity on host macrophages may, thus, find application in the therapy of leishmaniasis.

Induction of partial protection against Leishmania donovani by promastigote antigens in negatively charged liposomes.

Negatively charged liposomes, proposed as potential vaccine adjuvants, have been extensively studied in association with various antigens. In the present study, we investigated the adjuvanicity of negatively charged liposomes to enhance the protective immunity of membrane antigens of Leishmania donovani promastigotes (LAg). In comparison to the control mice immunized with phosphate-buffered saline and empty liposomes, immunization with free LAg led to significant levels of protection against infection with virulent promastigotes. Encapsulation of LAg in liposomes also induced effective protection. However, the level of protection by LAg-liposome was not significantly different from that induced by free LAg. Investigation of the immune responses showed, in contrast to free LAg, that immunization with LAg-liposome elicited strong antibody responses. IgG isotype analysis revealed the presence of all 4 isotypes. However, the titer of IgG1 was significantly higher than IgG2a, IgG2b, and IgG3. Following infection, stimulation of IgG and IgG isotypes did not differ in the different immunization groups. Delayed-type hypersensitivity (DTH) analysis after immunization showed significant induction by LAg and LAg-liposomes, in comparison to controls. With infection, again, the level of DTH in all the groups became almost comparable. Stimulation of insufficient cellular response, as reflected by DTH and potentiation of IgG1 over IgG2a, IgG2b, and IgG3 suggest a dominance of Th2 response with this liposome-antigen formulation, resulting in weak protection against visceral leishmaniasis.

Antileishmanial activities of stearylamine-bearing liposomes.

Here we report the activity of liposomes comprising egg phosphatidylcholine (PC) and stearylamine (SA) against Leishmania donovani parasites. Both promastigotes and intracellular amastigotes in vitro and in vivo were susceptible to SA-PC liposomes. A single dose of 55 mg of SA-PC liposomes/animal could significantly reduce the hepatic parasite burden by 85 and 68% against recent and established experimental visceral leishmaniasis, respectively, suggesting their strong therapeutic potential.

Differential decline in Leishmania membrane antigen-specific immunoglobulin G (IgG), IgM, IgE, and IgG subclass antibodies in Indian kala-azar patients after chemotherapy.

Pathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. Since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin G (IgG) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. Using leishmanial membrane antigenic extracts, we investigated the relative levels of specific IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera during disease, drug resistance, and cure. Acute-phase sera showed strong stimulation of IgG, followed by IgE and IgM and lastly by IgA antibodies. IgG subclass analysis revealed expression of all of the subclasses, with a predominance of IgG1 during disease. Following sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE, and IgG4 remained constant, while there was a decrease in the titers of IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1 was observed in these individuals. Cure, in both SAG-responsive and unresponsive patients, correlated with a decline in the levels of IgG, IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and the persistence, most importantly, of IgE and IgG4 following drug resistance, along with a decline in IgE, IgG4, and IgG1 with cure, demonstrate the potential of these isotypes as possible markers for monitoring effective treatment in kala-azar.

Immunoglobulin subclass distribution and diagnostic value of Leishmania donovani antigen-specific immunoglobulin G3 in Indian kala-azar patients.

Visceral leishmaniasis, or kala-azar, a fatal tropical disease, remains problematic, as early diagnosis is difficult and treatment often results in drug resistance and relapse. We have developed a sensitive enzyme-linked immunosorbent assay (ELISA), using leishmanial membrane antigenic extracts (LAg) to detect specific antibody responses in 25 untreated Indian visceral leishmaniasis patients. To investigate the pathogenetic significance of isotype markers in kala-azar, relative levels of specific immunoglobulin G (IgG), IgM, IgA, IgE, and IgG subclasses were analyzed under clinically established diseased conditions. Since LAg showed higher sensitivity for specific IgG than lysate, the immunoglobulin isotype responses were evaluated, with LAg as antigen. Compared to 60 controls, which included patients with malaria, tuberculosis, leprosy, and typhoid and healthy subjects, visceral leishmaniasis patients showed significantly higher IgG (100% sensitivity, 85% specificity), IgM (48% sensitivity, 100% specificity), and IgE (44% sensitivity, 98.3% specificity) responses. Low levels of IgA in visceral leishmaniasis patients contrasted with a 13-fold-higher reactivity in sera from patients with leprosy. Among IgG subclasses, IgG1, -3, and -4 responses were significantly higher in visceral leishmaniasis patients than in the controls. IgG2 response, however, was significantly higher (twofold) in leprosy than even visceral leishmaniasis patients. The rank orders for sensitivity (IgG = IgG1 = IgG3 = IgG4 > IgG2 > IgM > IgE > IgA) and specificity (IgM = IgG3 > IgE > IgG4 > IgG2 > IgG > IgG1 > IgA) for LAg-specific antibody responses suggest the potentiality of IgG3 as a diagnostic marker for visceral leishmaniasis.