Immunohistochemical Expression of Epidermal Growth Factor Receptor (EGFR) in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.

BACKGROUND: Increased epidermal growth factor receptor (EGFR) expression has been implicated in several tumors and is associated with increased tumor advancement as well as a potential drug target. The objective of the study was to compare the immunohistochemical expression of EGFR in oral squamous cell carcinoma (OSCC) with oral potentially malignant disorders (OPMDs) and their demographic and pathologic parameters. METHODS: This study was a comparative cross-sectional analytical study. It was conducted at the Department of Pathology, Peshawar Medical College, Riphah International University, Islamabad, Pakistan, from March 2021 to February 2022. The sample size was calculated through G Power. Thirty-eight cases of oral squamous cell carcinoma and 38 cases of oral potentially malignant disorders (OPMDs) were included in the study. Statistical analysis was performed using the Statistical Package for Social Sciences version 20.0. χ 2 tests and Fisher exact tests were applied to compare categorical variables. RESULTS: Mean age of OSCC was 61.6±13.9, with age range from 26 to 90 years. The male-to-female ratio for OSCC was 2.16:1. Buccal mucosa was the most common site involved (34.2%). The most common histologic type was well-differentiated OSCC (71.05%) followed by poorly differentiated (16%) and moderately differentiated (13.15%). The mean age of OPMDs cases was 59.16 ± 10.81 with a male-to-female ratio of 1:1.2. Buccal mucosa was the common site (55.3%), followed by the tongue (18.4%). The OPMDs with dysplasia were 55.2%, and without dysplasia were 44.8%. A total of 55.7% of cases of OSCC showed positive EGFR expression as compared with 36.9% OPMDs cases. A higher number of low-grade OSCC cases showed increased EGFR positivity (59.3%) as compared with high grade (45.45%). EGFR positivity in OPMD cases without dysplasia was 41.2% as compared with cases with dysplasia (33.3%). The EGFR expression in OPMD cases was higher in the ≤50 age group ( P =0.001) and in females ( P =0.032), which was statistically significant. CONCLUSIONS: EGFR expression by Immunohistochemistry may not be a helpful prognostic marker to determine the risk of OPMDs progressing to higher grades of dysplasia or invasive cancer. However, further studies relating this tumor marker to stage, lymph node metastasis, hematogenous metastasis, survival outcomes, and treatment response may give useful information regarding the utility of this marker.

Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial.

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes. Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05. Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39-7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy. Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients' subgroups characteristics that might benefit from administered therapy. Clinical Trial Registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678.

Malignant peripheral nerve sheath tumours in a patient with Neurofibromatosis-1.

Malignant peripheral nerve sheath tumour (MPNST) is an uncommon type of soft tissue tumour which most commonly arises in the setting of Neurofibromatosis-1 (NF-1) or in the presence of another nerve sheath tumour. NF-1 is an autosomal dominant syndrome which is diagnosed based on clinical criteria. People suffering from NF-1 are at a higher risk of developing tumours, especially MPNST. MPNST can occur anywhere along the distribution of nerve roots but most commonly involves the limbs and trunk. The prognosis of MPNST in the setting of NF-1 is grave as the distant metastasis develops earlier than non-syndromic cases. Pre-operative diagnosis is difficult as there is no gold standard radiologic technique or characteristic radiological features. The diagnosis is established after histological evaluation supplemented by immunohistochemistry of the tumour tissue. We present a case of a 38-year-old female, a known case of NF-1, who presented with a single, irregular, cystic swelling in the left flank which was increasing in size. The patient underwent complete surgical excision of a 6cm tumour which was diagnosed as MPNST after histopathological examination. The rare nature of this tumour makes the diagnosis and treatment extremely hard. Awareness regarding this disease should be increased so that proper treatment plans can be made.

Evaluation of gender trends in first authorship in nephrology publications in four major US journals in the last decade.

BACKGROUND: To date, no data exist on gender-related publication biases in nephrology. This study was conducted to determine whether gender differences exist in the current literature published in high-ranking US nephrology journals, and how they may have changed over time. METHODS: The PubMed search was performed using the easyPubMed package in R, which extracted all articles indexed in PubMed from 2011 to 2021 from the US nephrology journals with the highest impact factors, i.e., Journal of the American Society of Nephrology (JASN), American Journal of Nephrology (AJN), American Journal of Kidney diseases (AJKD), and the Clinical Journal of the American Society of Nephrology (CJASN). Gender with predictions > 90% were accepted and the remaining were manually identified. Descriptive statistical analysis was carried out on the data. RESULTS: We identified 11,608 articles. On average, the ratio of male to female first authors decreased from 1.9 to 1.5 (p < 0.05). Additionally, in 2011, women accounted for 32% of first authors, a number that rose to 40% in 2021. All but the American Journal of Nephrology showed a variation in the ratio of men to women first authors. For the JASN, the ratio changed from 1.81 to 1.58, p = 0.001, for CJASN, the ratio declined from 1.91 to 1.15, p = 0.005 and for AJKD, the ratio declined from 2.19 to 1.19, p = 0.002. DISCUSSION AND CONCLUSIONS: Our study shows that gender biases in publications continue to exist in first-author publications in high-ranking Nephrology journals published in the US; the gap is however closing. We hope this study lays the groundwork to continue following and evaluating gender trends in publication.

Comparison of PD-L1 Expression in Oral Squamous Cell Carcinoma and Premalignant Lesions of Oral Cavity.

OBJECTIVE: Objectives of this study were to compare  expression of Programmed Death-Ligand 1(PD-L1) protein in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorder (OPMD) cases; and to compare the PD-L1 protein expression in histological grades of OSCC and also in OPMD's with Dysplasia and without Dysplasia. MATERIALS & METHODS: In this study,  25 cases of Oral squamous cell carcinoms, 25 cases of Oral Potentially Malignant Disorders and 10 cases of non-neoplastic oral mucosa (control) cases were included. FFPE blocks of OSCC and OPMD cases were contributed by Department of Pathology, Histopathology Division,Pakistan Institute of Medical Sciences, Islamabad. Immunohistochemical staining of cases with PD-L1 monoclonal antibody (1:100; Dako) was carried out at Histopathology division , PMC Labs,  Peshawar Medical College,Peshawar, Riphah International University, Islamabad . Epithelial cells (membranous and cytoplasmic) positivity was observed for PD-L1 Antibody. Data was analyzed in SPSS version20. For qualitative variables frequencies and percentages were calculated whereas for quantitative variables means and standard deviations were recorded. The Chi-square test was applied to evaluate the significant difference in categorical variables . p-value of ≤0.05 was taken as significant. RESULTS: PD-L1 expression in OSCC cases turned out to be 48% (n=12/25) as compared to 8% of OPMD cases (n=2/25) with a significant p value of 0.002 and all non-neoplastic oral mucosa cases were negative. PD-L1 expression in high grade OSCC cases was quite high (61% n=11/18) as compared to low grade OSCC (14% n=1/7) cases with a significant p value of 0.035. CONCLUSION: A statistically significant increased PD-L1 expression was noted in  OSCC as compared to OPMD. Expression of PD-L1 was more intense in high grade OSCC cases. The relation of PD-L1 expression to age ,gender or location of OSCC and OPMD cases , and presence of dysplasia in OPMD cases was statistically not significant.

Hematologic Outcomes of COVID-19 Patients with and without G6PD Deficiency: A Comparative Study.

INTRODUCTION: Patients with multiple comorbidities who have coronavirus disease 2019 (COVID-19) have high morbidity and mortality. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to have an enhanced effect on coronavirus in an earlier study. METHODS: We conducted this comparative observational study to evaluate the effects of COVID-19 disease on G6PD deficiency based on the hematologic parameters, COVID-19-related hospitalizations, and mortality in the state of Qatar between January 2020 and May 2020 at four designated COVID-19 facilities. We identified 41 patients with G6PD deficiency who had documented COVID-19 infection. We compared the results with 241 patients with COVID-19 infection who tested negative for G6PD deficiency.: Results: Comparing the COVID-19 positive G6PD deficient with COVID-19 positive G6PD normal activity showed that G6PD normal group had higher white blood cell count (WBC), absolute neutrophil count (ANC), lymphocytes, eosinophils, and monocytes counts versus the G6PD deficient group (p < 0.001). CONCLUSIONS: When compared with COVID-19 patients with normal G6PD, patients with COVID-19 infection and G6PD deficiency had lower total WBC, ANC, lymphocyte, monocyte, and eosinophil counts. However, no evidence of increased hemolysis, thrombosis, morbidity, or mortality was observed in COVID-19 patients with G6PD deficiency.

Differentiation of Subjective Cognitive Decline, Mild Cognitive Impairment, and Dementia Using qEEG/ERP-Based Cognitive Testing and Volumetric MRI in an Outpatient Specialty Memory Clinic.

BACKGROUND: Distinguishing between subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia in a scalable, accessible way is important to promote earlier detection and intervention. OBJECTIVE: We investigated diagnostic categorization using an FDA-cleared quantitative electroencephalographic/event-related potential (qEEG/ERP)-based cognitive testing system (eVox® by Evoke Neuroscience) combined with an automated volumetric magnetic resonance imaging (vMRI) tool (Neuroreader® by Brainreader). METHODS: Patients who self-presented with memory complaints were assigned to a diagnostic category by dementia specialists based on clinical history, neurologic exam, neuropsychological testing, and laboratory results. In addition, qEEG/ERP (n = 161) and quantitative vMRI (n = 111) data were obtained. A multinomial logistic regression model was used to determine significant predictors of cognitive diagnostic category (SCD, MCI, or dementia) using all available qEEG/ERP features and MRI volumes as the independent variables and controlling for demographic variables. Area under the Receiver Operating Characteristic curve (AUC) was used to evaluate the diagnostic accuracy of the prediction models. RESULTS: The qEEG/ERP measures of Reaction Time, Commission Errors, and P300b Amplitude were significant predictors (AUC = 0.79) of cognitive category. Diagnostic accuracy increased when volumetric MRI measures, specifically left temporal lobe volume, were added to the model (AUC = 0.87). CONCLUSION: This study demonstrates the potential of a primarily physiological diagnostic model for differentiating SCD, MCI, and dementia using qEEG/ERP-based cognitive testing, especially when combined with volumetric brain MRI. The accessibility of qEEG/ERP and vMRI means that these tools can be used as adjuncts to clinical assessments to help increase the diagnostic certainty of SCD, MCI, and dementia.

Perioperative leadership in the non-operating room and ambulatory setting.

To create a successful ambulatory care center, healthcare systems need management that can understand and improve key ambulatory success factors such as quality of clinical care, clinical competence, regulatory compliance, financial management, and customer service. Effective leadership is a vital skill that can improve all these factors. This manuscript discusses successful perioperative leadership styles in the ambulatory setting and provides a framework for proven strategies that have improved patient care.

A Rare Symptomatic Case of Congenital Origin of Right Coronary Artery From Left Coronary Sinus.

An anomalous origin of the right coronary artery from the left coronary sinus is a rare congenital disorder, characterized by an asymptomatic presentation and an increased risk of myocardial infarction, arrhythmias, and sudden cardiac death. This disorder with an inter arterial course of the right coronary artery is subject to mechanical compression leading to various symptoms. Only a handful of studies are published related to the atypical origin of coronary arteries. Therefore, we present a case of a hospitalized adult diagnosed with an atypical origin of the right coronary artery from the left coronary sinus. A 51-year-old female presented with mid-sternal heaviness, pressure, and burning sensation, not accompanied by sweating, dizziness, or light-headedness. Biochemical studies revealed an elevated troponin 1 level of 0.12 ng/mL. A coronary arteriogram showed proximal stenosis of the right coronary artery. CT cardiac angiography revealed a large right coronary artery arising from the left cusp anterior to the left main coronary artery. The patient was treated with surgical revascularization therapy.

Comparative Analysis of Inhaled Insulin With Other Types in Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

To analyze the effect of Inhaled insulin in Type 1 Diabetes Mellitus and compare it with other routes of administration of Insulin. A systemic search was conducted from the following electronic databases: PubMed/Medline, Cochrane Library, and Google Scholar, from inception to 28th January 2022. All statistical analysis was conducted in Review Manager 5.4.1. All studies meeting inclusion criteria were selected. A random-effect model was used to pool the studies, and the result was reported in the Standard Mean Difference (SMD), Mean Difference (MD), and Risk Ratio (RR) with their corresponding 95% Confidence interval (CI). Thirteen randomized control trials were selected for our meta-analysis. Statistically significant results were obtained for comparing change in weight after insulin administration (MD= -1.08 [-1.21, -0.94]; p< 0.00001; I2= 74%). Other factors assessed were found to be non-significant like HbA1c (SMD= 0.03 [-0.80, 0.86]; p= 0.95; I2= 99%), fasting blood sugar (SMD= -0.31 [-1.52, 0.91]; p= 0.62; I2= 99%) and adverse effects (RR= 1.06 [0.97, 1.16]; p= 0.18; I2= 96%). In this systematic review and meta-analysis, we found that inhaled insulin is equally effective as subcutaneously administered insulin in patients with Type 1 Diabetes. The inhaled insulin was found to show less weight gain and fewer hypoglycemic shifts, with a similar effect on the blood glucose level. No significant difference was observed in the incidence of adverse events.

Meckel's diverticulum leading to ileo-ileal intussusception.

Intussusception secondary to Meckel's diverticulum is a rare entity in adults and hence, can be a challenging to accurately diagnose preoperatively. This case illustrates the clinical, imaging, operative, and histologic manifestations of a Meckel's diverticulum leading to a long segment ileo-ileal intussusception in an adult female patient presenting with symptoms of small bowel obstruction.

Breast T-Lymphoblastic Lymphoma Presenting as a Single Mass in a Young Female with Family History of Breast Cancer.

Breast involvement by lymphoma is rare, constituting ≤0.5% of all breast malignancies, with T-cell lymphomas, comprising 2.5 to 7.5% of all lymphomas involving breast. Several types of T-cell lymphomas have been reported in breast, including anaplastic large-cell lymphoma, breast implant associated anaplastic large cell lymphoma, peripheral T-cell lymphoma not otherwise specified, adult T-cell lymphoma/leukemia, NK/T-cell lymphoma, and T-lymphoblastic lymphoma. Breast involvement by T-lymphoblastic lymphoma is very unusual and when it is observed, it usually occurs as a secondary involvement by known lymphoma.We report the case of a 33-year-old woman with family history of breast cancer who presented with a single right breast mass which was diagnosed as T-lymphoblastic lymphoma. At presentation, the patient was feeling well and did not have any B symptoms or any other signs of lymphoma or leukemia. One month after diagnosis, the patient presented to the emergency room with chest pain and shortness of breath and was found to have a large mediastinal mass with both pleural and pericardial effusions. Subsequent evaluation of peripheral blood smear and bone marrow biopsy showed increased amount of blasts and involvement by T-lymphoblastic lymphoma. The patient was induced with cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone chemotherapy. After two-cycles of chemotherapy, a computed tomography of the thorax showed marked interval decrease in size of anterior mediastinal mass, suggestive of positive treatment response.Here, we report the first well documented case of T-lymphoblastic lymphoma presented as a single breast mass without history of B symptoms and perform an extensive English language literature review.

Eyelid Myokymia-a Presumed Manifestation of Coronavirus Disease 2019 (COVID-19).

The purpose of this study is to report eyelid myokymia in patients recently recovered from COVID-19 disease. A cohort of 15 patients who developed eyelid myokymia during or immediate post-recovery of systemic disease were evaluated. Demographic, clinical characteristics, effect of age, and hospitalization on the disease course were studied. The disease course was evaluated every month for 3 months period. All, except 2, patients had complete resolution of lid myokymia within 3 months of onset. Median [IQR] myokymia recovery time was 42 [31,60] days. Age and duration of hospitalization had a significant linear relationship with myokymia recovery time. Recovery was delayed by 2.64 days with every 1-year increment in age and by 6.19 days with every additional day of hospital stay. Recovery time was independent of severity of systemic disease (P = .055) and gender (P = 0.2). Eyelid myokymia can be a possible manifestation of COVID-19 recovery phase. While myokymia recovers gradually in all these patients, older age and a longer duration of hospitalization are associated with slower recovery.

A Novel Method of Quantifying the Choriocapillaris in Normal and Post-inflammatory Eyes.

OBJECTIVE: To assess the reliability and validity of gray level co-occurrence matrices (GLCM) in the quantification of choriocapillaris and describe GLCM features in normal and eyes with resolved acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis (SC). METHODS: In this, multicenter, reliability, validity and comparative study; OCTA was performed on eyes with resolved APMPPE and SC and normal individuals. CC texture classification, low flow area measurements and GLCM feature extraction were performed. RESULTS: A total of 13 normal, 8 APMPPE and 15 SC eyes were analyzed. All GLCM parameters demonstrated an excellent reliability. GLCM parameters were differently distributed across the three groups. Decision-tree based on the random forest predictive model provided an overall accuracy of 86% in classifying the three groups using GLCM features. CONCLUSION: These data demonstrated an excellent reliability and validity of GLCM features in quantifying the choriocapillaris in healthy and diseased eyes.

MALT lymphoma of the tongue: An unusual site that may present a diagnostic challenge.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-grade B cell lymphoma that can affect any organ, usually preceded by acquisition of MALT in response to antigenic stimulus provided by infections or autoimmune diseases. Most often, MALT lymphoma involves the stomach (about 35% of cases), followed by the ocular adnexal region, skin, lungs, and salivary glands, but virtually any extranodal site can be involved. MALT lymphomas are less common at sites of normal MALT tissue, such as Waldeyer ring and the ileocecal region of the gastrointestinal tract. Lymphomas involving the tongue are extremely rare and represent approximately 3% of all lymphomas involving the head and neck region. In this study, we discuss potentially challenging diagnostic aspects of MALT lymphoma involving the tongue and review and summarize the available literature about this topic.

Intensive Poultry Farming Practices Influence Antibiotic Resistance Profiles in Pseudomonas aeruginosa Inhabiting Nearby Soils.

BACKGROUND: The drastic increase in use of antibiotics as a mandatory part of production in poultry and livestock has led to the development of bacterial resistance against antibiotics. The spread of resistant bacteria from poultry to humans increases the risk of treatment failure by antibiotics because of resistance genes transfer. STUDY OBJECTIVE: The objective of the study was to estimate and compare the P. aeruginosa resistance profile collected from areas around the poultry farm premises and areas at least 500 meters away from the nearest poultry farm. We studied the effect of antibiotic usage in farms on the bacterial profile present in the upper layer of soil. METHODOLOGY: A total of 1,200 moist soil samples were collected from areas within a 25 meters range of poultry farms and areas that had no poultry farms in its 500 meters vicinity. P. aeruginosa was cultured and isolated. The antibiotic susceptibility profile was carried out by Kirby-Bauer disc diffusion method and results were analyzed according to CLSI guidelines. Statistical analysis was carried out to check the significance of results. RESULTS: A total of 300 P. aeruginosa isolates were isolated, among which 140 isolates were isolated from areas around the poultry farm premises and had higher prevalence of antibiotic resistance. A total of 160 isolates were isolated from areas outside the poultry farm range. Resistance was not as high as in the isolates from around the farm. The ESBL production was higher in the isolates that were in close contact with the poultry farm as compared to the isolates away from the farm. CONCLUSION: Use of antibiotics in the poultry farm for production significantly increases the resistance in bacterial strains present in the upper layer of soil around the poultry farm within at least a 25 meter range.

Coronavirus disease 2019 in solid organ transplant recipients in the setting of proactive screening and contact tracing of Qatar.

BACKGROUND: Clinical data on Coronavirus Disease 2019 (COVID-19) in solid organ transplant (SOT) recipients are limited. We herein report the initial clinical experience with COVID-19 in SOT recipients in Qatar. METHODS: All SOT recipients with laboratory-confirmed COVID-19 up to May 23, 2020 were included. Demographic and clinical data were extracted retrospectively from the hospital's electronic health records. Categorical data are presented as frequency and percentages, while continuous variables are summarized as medians and ranges. RESULTS: Twenty-four SOT recipients with COVID-19 were identified (kidney 16, liver 6, heart 1, and liver and kidney 1). Organ transplantation preceded COVID-19 by a median of 60 months (range 1.7-184). The median age was 57 years (range 24-72), and 9 (37.5%) transplant recipients were females. Five (21%) asymptomatic patients were diagnosed through proactive screening. For the rest, fever (15/19) and cough (13/19) were the most frequent presenting symptoms. Five (20.8%) patients required invasive mechanical ventilation in the intensive care unit (ICU). Eleven (46%) patients developed acute kidney injury, including three in association with drug-drug interactions involving investigational COVID-19 therapies. Maintenance immunosuppressive therapy was modified in 18 (75%) patients, but systemic corticosteroids were not discontinued in any. After a median follow-up of 226 days (26-272), 20 (83.3%) patients had been discharged home, 2 (8.3%) were still hospitalized, 1 (4.2%) was still in the ICU, and 1 (4.2%) had died. CONCLUSIONS: Our results suggest that asymptomatic COVID-19 is possible in SOT recipients and that overall outcomes are not uniformly worse than those in the general population. The results require confirmation in large, international cohorts.

An Uncharacteristic Presentation of Evans Syndrome Following Treatment With Dupilumab.

Evans syndrome is a rare autoimmune disorder where patients develop autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and less commonly immune neutropenia. Patients typically present with fatigue, pallor, jaundice, petechiae, or epistaxis. A 27-year-old man with a history of atopic dermatitis for which he recently began treatment with dupilumab presented to the emergency department with a headache and blurry vision. Multiple Roth spots were seen on fundoscopic examination. Laboratory studies were consistent with warm AIHA, confirmed by a positive direct antiglobulin test (DAT), and severe thrombocytopenia. He was diagnosed with Evans syndrome. He was treated with corticosteroids, rituximab, and intravenous immunoglobulin (IVIG). His recovery was prolonged with the slow improvement of anemia and thrombocytopenia. This is an atypical presentation of Evans syndrome with isolated symptoms of new-onset blurry vision and headache along with the finding of Roth spots. Another interesting feature in the case is the recent use of dupilumab. Dupilumab is a monoclonal antibody that inhibits the T-helper cells type 2 (Th2) signaling pathway by blocking interleukin (IL)-4 and IL-13 binding. This alteration in the immune response could have a role in the development of Evans syndrome.