The Neurologist

Predictors of Good Outcomes in Stroke Thrombolysis Guided by Tissue-Window Background: Recently studies suggested that assessment of tissue-window can effectively guide thrombolysis in acute ischemic stroke patients with unknown time of onset or late presenting. This study aimed to evaluate predictors of good outcomes from thrombolysis in these patients. Methods: Acute ischemic stroke patients received thrombolysis guided by computed tomography perfusion (CTP) from October 2018 to August 2019 were reviewed. Baseline characteristics and outcomes were collected. Good outcomes were defined as modified Rankin scale scores of 0 to 2 at 90 days. Logistic regression analysis was performed and the receiver operating characteristics analysis was used to determine cut-off values for the predictors of outcomes. Results: Sixty-three patients were enrolled. The median age was 64 (interquartile range 57.75 to 72.5) years. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 8 (interquartile range 3 to 13) and 41 (65.1%) patients had a good outcome at 90 days. Multivariate regression analysis showed smaller perfusion lesion (the sum of ischemic penumbra and infarcted core) (odds ratio: 0.961; 95% confidence interval, 0.931-0.992; P=0.013) and lower baseline NIHSS score (odds ratio: 0.759; 95% confidence interval, 0.644-0.895; P=0.001) were significant predictors for good outcomes. Receiver operating characteristics analysis was utilized to define optimal cut-off values for perfusion lesion [cut-off, 59 mL; area under curve (AUC), 0.761; sensitivity, 0.57; specificity, 0.93; P=0.001], ischemic penumbra (cut-off, 43.5 mL; AUC, 0.761; sensitivity, 0.62; specificity, 0.90; P=0.001), infarcted core (cut-off, 9.5 mL; AUC, 0.665; sensitivity, 0.43; specificity, 0.93; P=0.035), and baseline NIHSS score (cut-off, 8.5; AUC, 0.880; sensitivity, 0.81; specificity, 0.88; P<0.001). Conclusions: This study suggested that smaller perfusion lesion and lower baseline NIHSS score may be helpful to predict favorable prognosis of stroke patients who receive thrombolysis guided by tissue-window.

Effect of Low-Frequency rTMS and Intensive Speech Therapy Treatment on Patients With Nonfluent Aphasia After Stroke Background: To observe the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with nonfluent aphasia after stroke. Materials and Methods: Thirty patients were divided into control, rTMS, and 2 times a day low-frequency rTMS (2rTMS) groups, and all 3 groups had intensive speech therapy (ST). Patients were assessed by western aphasia battery (WAB) scale. The spontaneous language, listening comprehension, retelling, and naming were scored, respectively. The expression of brain-derived neurotrophic factor (BDNF) in peripheral blood was detected by enzyme-linked immunosorbent assay. Results: There was significant difference in aphasia quotient after treatment in the 3 groups. The values of the 4 dimensions in the WAB score of the rTMS group were higher than those in the control group. The WAB scores in the 2rTMS group were higher than those in the rTMS group. After 2 weeks treatment, the BDNF levels in the rTMS group and the 2rTMS group were significantly higher than those in the control group. Four weeks later, the 2rTMS group was significantly increased compared with the control group and the rTMS group. Conclusions: Low-frequency rTMS combined with conventional ST treatment can effectively improve the language function of patients with nonfluent aphasia after stroke. Two times a day low-frequency rTMS therapy combined with conventional ST treatment can improve the language function of patients with nonfluent aphasia after stroke more effectively and it also promote the expression of BDNF more effectively, thereby improving nerve repair and protecting brain tissue.

Comparative Evaluation of Stroke Awareness of Individuals Whose First-Degree Relatives had a Stroke and that of Individuals Whose First-Degree Relatives Did Not Objective: To assess the stroke awareness levels of individuals whose first-degree relatives had a stroke and to compare the results with those of individuals whose first-degree relatives did not have a stroke. Materials and Methods: This cross-sectional study was conducted between March and May 2019, with first-degree relatives of patients who had a stroke (group 1) and a comparable set of individuals whose first-degree relatives did not have a stroke (group 2). Participants were asked to complete a questionnaire asking about signs and symptoms, risk factors, treatment options, information sources, responses after the development of stroke, and early treatment of stroke. Results: In response to the questions about the signs and symptoms of stroke, group 1 mentioned dizziness and comprehension disorder as a symptom of stroke more frequently than the other group. Stress was the second most frequently mentioned risk factor (by 81% of group 1 and 80.5% in group 2). When the participants were asked about the sources of information about stroke, family circle and friends were the most frequently mentioned sources for both groups. Conclusion: The present study can serve as a guide in planning training to improve stroke awareness in the future, especially by including individuals whose first-degree relatives had a stroke.

Neurological Manifestations of SARS-CoV-2: A Narrative Review Background: Coronavirus disease 2019 (COVID-19) pandemic started as an outbreak in China and soon crossed borders to affect the populations in all countries of the world. During the initial course of the disease, COVID-19 was perceived as a pneumonia-like illness. However, recent findings of COVID-19 patients suggest that the virus has the potential to disseminate to different tissues and organs, and cause significant complications. Summary: Neurological symptoms are of great significance as these usually present in and complicate critical cases. Many case reports and case series have documented the findings of neurological complications in COVID-19 patients. From the existing data, the most frequent symptoms in these patients were broadly classified into the central nervous system (CNS), peripheral nervous system, and skeletal muscular symptoms. CNS symptoms include meningitis, encephalitis, cerebrovascular complications, peripheral nervous system symptoms include anosmia, ageusia, and skeletal muscular symptoms include myalgias. It is postulated that the cause may be direct CNS injury through blood and neuronal pathways or indirectly because of an immune-mediated response, hypoxia caused by decreased oxygen saturation, or by the binding of subacute respiratory syndrome-coronavirus-2 to the host angiotensin-converting enzyme-2 receptors. Striking radiologic findings in COVID-19 patients with neurological symptoms have also emerged. Conclusions: As subacute respiratory syndrome-coronavirus-2 may potentially have lethal implications on the nervous system, it is important that neurologists are better informed about the spectrum of clinical manifestations, radiologic findings, and likely mechanisms of injury. Understanding the symptoms and radiologic imaging allows clinicians to consider brain imaging in any patient with suspected COVID-19 and neurological symptoms.

True Restriction in Diffusion-Weighted Imaging in a Mistreated Patient With Phenylketonuria Introduction: Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism and causes neurological manifestations because of excessive accumulation of phenylalanine (PHE). It can also affect adult patients who discontinue their treatment, even if they had been under adequate metabolic control during childhood. For that reason, it is recommended that PKU treatment should be continued throughout life and target PHE levels for adult patients should range between 120 and 600 μmol/L. Case Report: The authors present an adult patient with PKU who discontinued treatment and developed cognitive dysfunction because of high blood levels of PHE. Brain magnetic resonance imaging (MRI) of the patient was characteristic for PKU, presenting periventricular and callosal white matter hyperintensities in T2 and fluid-attenuated inversion recovery sequences, which were additionally associated with true restriction in diffusion-weighted imaging sequence, a far less recognized PKU neuroimaging feature. Discussion: Cognitive dysfunction and psychiatric disorders can be present in adult patients with PKU who discontinue treatment and have poor PHE metabolic control. The presence of white matter hyperintensities in T2 and fluid-attenuated inversion recovery MRI-sequences is a well-described neuroimaging feature of PKU, but diffusion-weighted imaging sequence may also be reliable in detecting brain lesions in patients with PKU. PKU lesions should be considered in the differential diagnosis of true diffusion restriction in brain MRI of patients with PKU history or those who might have escaped newborn screening diagnosis but present neurocognitive dysfunction. Appropriate treatment for the management of PKU should be initiated for the reversal of the clinical and neuroimaging findings.

Huge Free-Floating Thrombus in the Internal Carotid Artery Under Duplex Ultrasound Surveillance: A Case Report Introduction: Carotid free-floating thrombus (FFT) is an unusual finding in acute ischemic stroke. Atherosclerosis is the most common etiology of FFT formation. Case Report: Here we report a 42-year-old male patient admitted to our department with left temporal and parietal lobe ischemic stroke with normal magnetic resonance angiography. A huge FFT in the left internal carotid artery were found by duplex ultrasound. Acute thrombosis based on atherosclerotic plaque were considered as the reason of this embolization. The thrombus shrunk significantly under anticoagulation and antiplatelet treatment. Conclusions: Evaluation of the intracranial vessel in the emergency is not enough and early carotid duplex ultrasound can help find of the FFT in time, which help to choose the early intervene by neurosurgeon. Early antithrombotic treatment can be a safe treatment option for reducing huge thrombus based on the nature of thrombus formation. Computed tomography angiography and high-resolution magnetic resonance imaging to certify the character of the plaque are recommended for plaque evaluation.

Acute Fluctuant Neurological Symptoms in Stable Chronic Cryptococcus gattii Cryptococcomas: A Novel Disease Complication Background: Cryptococcus, a yeast-like fungus, is the most common cause of fungal meningitis worldwide. The Cryptococcus gattii variety is concentrated in Australia has a greater propensity to infect immunocompetent hosts, cause meningitis and form crytococcomas. This case presents a novel disease complication, that is, acute neurological symptoms without seizures, disease progression or reactivation. Case Presentation: A 58-year-old immunocompetent male was brought to the emergency department with dysarthria and right arm paraesthesias. Computed tomography of the brain brain and magnetic resonance imaging revealed no stroke but found several previously identified crytococcomas that demonstrated no interval change. Blood tests and lumbar puncture found only a low cryptococcal antigen complex titer (CRAG) (1:10) and a negative cell culture. He had remained compliant on his maintenance fluconazole therapy and had no immunocompromise or seizure activity. He was initially treated as a relapse of cryptococcal disease and restarted on induction therapy but after the cell culture returned negative and the symptoms resolved over the following days he was reverted back to maintenance therapy. Discussion and Conclusions: Central nervous system cryptococcomas are difficult to treat, chronic infections, that in our patient had lasted over 10 years despite treatment compliance. A true cryptococcal meningitis relapse is indicated by positive cell cultures in previously sterile fluid but cryptococcoma progression is measured by serial magnetic resonance imaging or computed tomography scans. In the case of progression or relapse induction and consolidation therapy should be restarted. Our patient demonstrated neither relapse nor progression but presented with a novel disease complication of acute fluctuating neurology in chronic stable cryptococcomas.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Academic Medicine

Editorial Decision Making for Academic Medicine, 2021 No abstract available

Acknowledgment of Academic Medicine Reviewers No abstract available

Trust Is Transparency: Clarify the Clerkship Grading Scale No abstract available

In Reply to Kates No abstract available

Bringing Patient Perspective to the Forefront of High-Value Care No abstract available

In Reply to Daigle and Anand No abstract available

Exposure to Health Care Economics and Policy in Medical School Curricula as an Avenue to Improve Patient Advocacy No abstract available

A Critical Need for Progress in Implementing Education in Health Care Delivery Science No abstract available

Academic Medicine and the Quandary of Term Limits No abstract available

In Reply to Balon No abstract available

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

Telephone consultation 11855 int 1193,

Therapeutics

Leucine and Sildenafil Combination Therapy Reduces Body Weight and Metformin Enhances the Effect at Low Dose: A Randomized Controlled Trial Background: This study evaluated the potential of activating the fuel-sensing enzymes Adenine monophosphate (AMP)-activated protein kinase and the deacetylase sirtuin1, to promote weight loss. We tested the efficacy of a fixed dose combination of the amino acid leucine and 2 well-characterized agents with established safety profiles to modulate energy metabolism and facilitate weight loss. Study Question: Will a combination of l-leucine with low-dose metformin and sildenafil produce a novel synergistic interaction that reduces body weight? Study Design: We conducted a 24-week randomized controlled trial evaluating the effect on weight loss of leucine 1.1 g and sildenafil 1.0 mg or 4.0 mg, with and without metformin 500 mg (Leu/Sil 1.0, Leu/Sil 4.0, Leu/Met/Sil 1.0, and Leu/Met/Sil 4.0 twice/day). We enrolled 267 participants who were 18–65 years of age without diabetes and with the body mass index (BMI) of 30–45 kg/m2. Measures and Outcomes: The primary endpoint was percentage weight change after 24 weeks. Adverse events were evaluated. The primary analysis was performed using the perprotocol population analysis of covariance estimation. Subgroup analyses of patients residing above certain threshold limits at baseline and in populations at increased risk of obesity were assessed post-hoc as exploratory end points. Results: Placebo-adjusted mean bodyweight reductions in the Leu/Met/Sil 1.0, Leu/Met/Sil 4.0, and Leu/Sil 4.0 groups were −1.99%, −1.69%, and −1.67% (P = 0.015, 0.035, and 0.036, respectively). The most common adverse events were gastrointestinal-related and occurred in the metformin-treated groups consistent with metformin treatment. In African Americans, Leu/Met/Sil 1.0 produced 5.4% mean weight loss. In participants with BMI <40 kg/m2 treated with Leu/Met/Sil 1.0, the weight loss increased to 2.84%, particularly in participants with baseline insulin ≥12mU/L (3.5%). Conclusions: Leu/Met/Sil 1.0 and 4.0 and Leu/Sil 4.0 reduced body weight, but Leu/Met/Sil 1.0 was associated with robust weight loss in African Americans, and individuals with BMI 30–39.9 kg/m2, especially participants with hyperinsulinemia.

Inappropriate Use of Aztreonam Background: Aztreonam is not a preferred empiric antibiotic because of variable susceptibilities compared with alternative agents. In addition, it has no Gram-positive activity, necessitating coadministration with vancomycin when used empirically, and is more costly when compared with other Gram-negative active agents. Aztreonam is often given to patients with a reported penicillin allergy without further investigation into the reaction or other relevant allergy information. Study Question: How frequently is aztreonam being used inappropriately? Study Design: We conducted a retrospective chart review at an academic medical center to assess the appropriateness of our aztreonam use. Measures and Outcomes: Our primary outcome was frequency of appropriate aztreonam use, based on a true IgE-mediated allergy reported for each patient. We evaluated whether the patients had tolerated a beta-lactam in the past, and what the reported allergic reaction was. Results: We included 165 patients and found that 46.7% of our aztreonam use was inappropriate, based on previous use of a beta-lactam, or no documentation of an IgE-mediated response. Of the patients with a documented beta-lactam allergy, 63 (38.2%) patients had no allergy manifestation listed, and 37 (22.4%) patients had a non–IgE-mediated allergy manifestation. Of the total population, 61 (37%) patients had tolerated a beta-lactam in the past. Conclusions: Aztreonam should be avoided, except in the case of a true IgE-mediated allergic reaction. Our goal was to reduce the inappropriate use of aztreonam at our institution by one or more of the following: educating providers, reviewing aztreonam orders, requiring answering of order questions, or requiring an indication for use. Penicillin skin testing and desensitization are options as well.

Prevalence of Colorectal Neoplasms and Mortality in New Users of Low-Dose Aspirin With Lower Gastrointestinal Bleeding Background: Aspirin inhibits platelet function and may therefore accelerate early lower gastrointestinal bleeding (LGIB) from colorectal cancer (CRC) precursor polyps. The bleeding may increase endoscopic polyp detection. Study Question: To estimate the prevalence of polyps and CRC comparing new users of low-dose aspirin with nonusers who all received a diagnosis of LGIB and to investigate the mortality among these patients. Study Design: Using Danish nationwide health registries, we conducted a cohort study (2006–2013) of all new aspirin users who also received a diagnosis of LGIB (n = 40,578). Each new user was matched with 5 nonusers with LGIB by gender and age at the LGIB diagnosis date. Measures and Outcomes: We computed the prevalence and prevalence ratios (PRs) of colorectal polyps and CRCs, and the mortality ratios within 6 months after the LGIB, comparing new users with nonusers. Results: We identified 1038 new aspirin users and 5190 nonusers with LGIB. We observed 220 new users and 950 nonusers recorded with endoscopically detected polyps. New aspirin users had a higher prevalence of conventional {PR = 1.28 [95% confidence interval (CI): 1.06–1.55]} and serrated [PR = 1.31 (95% CI: 0.95–1.80)] polyps. New users and nonusers had a similar prevalence of CRC [PR = 1.04 (95% CI: 0.77–1.39)]. However, after stratifying by location of CRC, the prevalence of proximal tumors was lower [PR = 0.71 (95% CI: 0.35–1.43)] in new users than in nonusers. No difference in mortality was observed. Conclusions: These findings indicate that new use of low-dose aspirin is associated with an increased detection of colorectal polyps compared with nonuse.

Antithrombotic Therapy and Outcomes of Patients With New-Onset Transient Atrial Fibrillation After ST-Segment Elevation Myocardial Infarction Background: Atrial fibrillation (AF) is a common complication of ST-segment elevation myocardial infarction (STEMI), and AF might require anticoagulant treatment in some conditions. Study Question: There are no clear recommendations about vitamin K antagonist (VKA) use in patients with STEMI who complicated with new-onset transient AF. In this study, we examined the association of concomitant use of VKA and dual antiplatelet therapy (DAPT) with clinical outcomes of this patient population. Study Design: A total of 4086 patients with STEMI who underwent primary percutaneous coronary intervention retrospectively investigated. Among these patients, a total of 286 patients who developed new-onset transient AF during hospitalization were enrolled. VKA group consisted of 116 patients treated with warfarin, aspirin, and clopidogrel, and DAPT group consisted of 170 patients treated with aspirin and clopidogrel. Measures and Outcomes: One-year mortality, ischemic stroke, major, and minor bleeding were determined as clinical outcomes. Results: Although VKA group had proportionally lower mortality (17.2% vs. 20.0%) and ischemic stroke (7.8% vs. 11.8%) compared with DAPT group, the differences did not reach to statistical significance, whereas the 1-year major bleeding had higher rates at VKA group and that had 3.5-times higher major bleeding than DAPT group. This relationship was persisted after multivariable analysis (hazard ratio = 3.37, 95% CI, 1.76–10.04, P = 0.012). Conclusions: There is not a widely accepted treatment algorithm in patients with STEMI who complicated with new-onset AF in clinical guidelines. The current study indicated that transient form of new-onset AF might not require long-term VKA. Besides, addition of VKA to DAPT therapy may increase the rates of major and minor bleeding.

Topical Nifedipine for the Treatment of Pressure Ulcer: A Randomized, Placebo-Controlled Clinical Trial Background: Effect of nifedipine on pressure ulcer (PU) healing has not been evaluated in the human subjects yet. Study question: In this study, the effect of topical application of nifedipine 3% ointment on PU healing in critically ill patients was investigated. Study design: This was a randomized, double-blind, placebo-controlled clinical. Measures and outcomes: In this study, 200 patients with stage I or II PU according to 2-digit Stirling Pressure Ulcer Severity Scale were randomized to receive topical nifedipine 3% ointment or placebo twice daily for 14 days. Changes in the size and stage of the ulcers were considered as primary outcome of the study. The stage of the ulcers at baseline and on day 7 and day 14 of study was determined by using 2-digit stirling scale. In addition, the surface area of the wounds was estimated by multiplying width by length. Results: In total, 83 patients in each group completed the study. The groups were matched for the baseline stage and size of PUs. Mean decrease in the stage of PU in the nifedipine group was significantly higher than the placebo group on day 7 (−1.71 vs. −0.16, respectively, P < 0.001) and day 14 (−0.78 vs. −0.09, respectively, P < 0.001). Furthermore, the mean decrease in the surface area of PU was significantly higher in the nifedipine group compared with the placebo group on day 7 (−1.44 vs. −0.32, respectively, P < 0.001) and day 14 (−2.51 vs. −0.24, respectively, P < 0.001) of study. Conclusions: Topical application of nifedipine 3% ointment for 14 days significantly improved the healing process of stage I or II PUs in critically ill patients.

Comparing Nonopioids Versus Opioids for Acute Pain in the Emergency Department: A Literature Review Background: Pain is the most common reason for patient visits in the emergency department (ED). Opioids have been long considered the standard of care for acute pain in the ED. Because of the opioid crisis, investigation and implementation of novel practices to manage pain is needed. The use of various nonopioids has been suggested as a plausible alternative to opioids, with emerging literature to support its use for acute pain in the ED. Study Question: To evaluate the safety, efficacy, opioid-sparing effects of nonopioids in patients who present with acute pain in the ED. Data Sources: We systematically searched PubMed and EMBASE (July 1970 to January 2019). Study Design: Randomized controlled trials that evaluated nonopioids versus opioids in the ED were eligible. The clinical outcomes measured were change in pain scores compared with baseline, the incidence of adverse events, and use of rescue analgesia. Results: Twenty-five randomized controlled trials that evaluated the use of nonopioids in 2323 patients [acetaminophen (APAP) (n = 651), diclofenac (n = 547), ketamine (n = 272), ketorolac (n = 225), lidocaine (n = 219), ibuprofen (n = 162), ibuprofen & APAP (n = 162), hydroxyzine & dihydroergotamine (n = 85)] met inclusion criteria. Four trials found significant greater reductions in pain scores, favoring nonopioids. In all trials, the duration of pain relief provided by nonopioids was not sustained over an extended period. Eighteen trials reported no significant differences in reduction of pain scores. Two trials reported improved pain reduction with opioids and one trial reported noninferiority. Conclusions: Evidence from primary literature suggests that nonopioids could be a feasible alternative to opioids for management of acute pain in the ED as it is effective, safe, and decreases the need for rescue analgesia.

Treatment Failures of Direct Oral Anticoagulants Background: Use of direct oral anticoagulants (DOACs) has increased over the years, because they have become a safe and effective alternative to the Vitamin-K antagonists in various clinical scenarios. With their increased use, reports have emerged describing their failure. Study Question: What are the patient characteristics and clinical settings in which DOAC treatment failure manifests? Data Sources: We searched published reports in Google Scholar, PubMed, MEDLINE, and Embase from the introduction of DOACs in any therapy until March 2019. Study Design: Information on patient characteristics, comorbidities, primary anticoagulation indications, pharmacologic treatment, and outcomes were collected. Primary endpoints were new thrombus formation, failure of resolution of an existing thrombus, or discovery of subtherapeutic drug level. Other endpoints were time to treatment failure, manifestations of treatment failure, and new treatment after DOAC failure. Results: Our search yielded 51 manuscripts, describing 79 patients who exhibited DOAC failure. The most common treatment failures were in patients with antiphospholipid syndrome (44.3%), atrial fibrillation (30.4%), and deep venous thrombosis (6.3%). There was a trend toward higher failure rate for rivaroxaban (65.8%) followed by dabigatran (27.8%), apixaban (7.6%), and then edoxaban (1.3%). Each agent had different median failure times. Most common manifestations of treatment failure were stroke/transient ischemic attack (20.3%), pulmonary embolism (19.0%), and deep venous thrombosis (19.0%). More than half of patients were transitioned to a Vitamin-K antagonist after DOAC failure (55.7%). Conclusions: Our analysis illustrates that DOACs may fail in the setting of Food and Drug Administration and non–Food and Drug Administration- approved indications. In clinical practice, it may be best to choose between available anticoagulant drugs on a case-by-case basis.

Sodium–Glucose Cotransporter-2 Inhibitors and the Risk of Amputation: What Is Currently Known? Background: Diabetes mellitus is a major cause of morbidity and mortality in the United States. Twelve medication classes on the market reduce serum glucose including sodium–glucose cotransporter-2 (SGLT2) inhibitors. Potential benefits of these agents include improved glycemic control, weight loss, reduction in blood pressure, and possible reduction in cardiovascular events in patients with elevated cardiovascular risk. Areas of Uncertainty: Recently, several adverse events have been identified including increased possible risk of amputation associated with SGLT2 inhibitor therapy. Data Source: We conducted a review of published literature and identified 32 trials reviewing incidence of SGLT2 inhibitor-related amputation. Results: The potential increased risk for amputation is mostly of the lower extremities. Of the SGLT2 inhibitors currently available, canagliflozin has the highest association with an increased risk of lower extremity amputation and is the only agent with a Food and drug Administration Black Box Warning. Most canagliflozin amputation occurred in a single study. Risk factors for amputation with SGLT2 inhibitors may include those who have a history of amputations, susceptible to foot ulcers and those with baseline cardiovascular disease. Conclusions: For at-risk patients who desire an agent from this drug class, empagliflozin or dapagliflozin should be considered, as studies have not found a significant increase in amputations when compared with placebo or in retrospective reviews. Despite the increased risk of amputation found with canagliflozin, providers can use SGLT2 inhibitors with frequent monitoring to safely manage diabetes in low-risk patients. Patient education on associated risks is warranted. Diabetes educators can inform patients of risk factors to assist with monitoring.

Drug Repositioning in Oncology Background: The worldwide increase in the occurrence of cancer associated with the limitations of immunotherapy and the emergence of resistance have impaired the prognosis of cancer patients, which leads to the search for alternative treatment methods. Drug repositioning, a well-established process approved by regulatory agencies, is considered an alternative strategy for the fast identification of drugs, because it is relatively less costly and represents lower risks for patients. Areas of Uncertainty: We report the most relevant studies about drug repositioning in oncology, emphasizing that its implementation faces financial and regulatory obstacles, making the creation of incentives necessary to stimulate the involvement of the pharmaceutical industry. Data Sources: We present 63 studies in which 52 non-anticancer drugs with anticancer activity against a number of malignancies are described. Therapeutic Innovations: Some have already been the target of phase III studies, such as the Add-Aspirin trial for nonmetastatic solid tumors, as well as 9 other drugs (aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, and sertraline) in the CUSP9* clinical trial for the treatment of recurrent glioblastoma. Others have already been successful in repositioning such as thalidomide, zoledronic acid, celecoxib, methotrexate, and gemcitabine. Conclusions: Therefore, drug repositioning represents a promising alternative for the treatment of oncological disorders; however, the support from funding agencies and from the government is still needed, the latter regarding regulatory issues.

A New Safety Scoring System for the Use of Psychotropic Drugs During Lactation Background: Psychotropic drugs are frequently used to treat postpartum women with psychiatric diagnoses, especially psychotic disorder, major depression, and bipolar mood episodes. Pharmacotherapy in breastfeeding mothers is a major challenge. Study Question: This article presents a new safety scoring system for the use of psychotropic drugs during lactation. Study Design: The scoring system is based on the following 6 safety parameters: reported total sample, reported maximum relative infant dose, reported sample size for relative infant dose, infant plasma drug levels, prevalence of reported any adverse effect, and reported serious adverse effects. The total score ranges from 0 to 10. Higher scores represent a higher safety profile. Results: According to this scoring system, sertraline and paroxetine, respectively, had the highest scores representing "very good safety profile." Citalopram, olanzapine, and midazolam were assigned to "good safety profile." Among drugs evaluated in this article, trifluoperazine, aripiprazole, amisulpride, clozapine, doxepin, zaleplon, and zolpidem are not recommended owing to safety scores ≤3. Conclusions: Most psychotropic drugs examined in this article have "moderate" or "low" safety profile.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

Telephone consultation 11855 int 1193,

Healthcare Quality (JHQ)

Leadership Lessons From COVID-19 and the Path Forward No abstract available

Processes for Trauma Care at Six Level I Trauma Centers During the COVID-19 Pandemic Introduction: As the COVID-19 pandemic spread, patient care guidelines were published and elective surgeries postponed. However, trauma admissions are not scheduled and cannot be postponed. There is a paucity of information available on continuing trauma care during the pandemic. The study purpose was to describe multicenter trauma care process changes made during the COVID-19 pandemic. Methods: This descriptive survey summarized the response to the COVID-19 pandemic at six Level I trauma centers. The survey was completed in 05/2020. Questions were asked about personal protective equipment, ventilators, intensive care unit (ICU) beds, and negative pressure rooms. Data were summarized as proportions. Results: The survey took an average of 5 days. Sixty-seven percent reused N-95 respirators; 50% sanitized them with 25% using ultraviolet light. One hospital (17%) had regional resources impacted. Thirty-three percent created ventilator allocation protocols. Most hospitals (83%) designated more beds to the ICU; 50% of hospitals designated an ICU for COVID-19 patients. COVID-19 patients were isolated in negative pressure rooms at all hospitals. Conclusions: In response to the COVID-19 pandemic, Level I trauma centers created processes to provide optimal trauma patient care and still protect providers. Other centers can use the processes described to continue care of trauma patients during the COVID-19 pandemic.

Nurse Burnout Predicts Self-Reported Medication Administration Errors in Acute Care Hospitals Background: Every one out of 10 nurses reported suffering from high levels of burnout worldwide. It is unclear if burnout affects job performance, and in turn, impairs patient safety, including medication safety. The purpose of this study is to determine whether nurse burnout predicts self-reported medication administration errors (MAEs). Methods: A cross-sectional study using electronic surveys was conducted from July 2018 through January 2019, using the Copenhagen Burnout Inventory. Staff registered nurses (N = 928) in acute care Alabama hospitals (N = 42) were included in this study. Descriptive statistics, correlational, and multilevel mixed-modeling analyses were examined. Results: All burnout dimensions (Personal, Work-related, and Client-related Burnout) were significantly correlated with age (r = −0.17 to −0.21), years in nursing (r = −0.10 to −0.17), years of hospital work (r = −0.07 to −0.10), and work environment (r = −0.24 to −0.57). The average number of self-reported MAEs in the last 3 months was 2.13. Each burnout dimension was a statistically significant predictor of self-reported MAEs (p < .05). Conclusions: Nurse burnout is a significant factor in predicting MAEs. This study provides important baseline data for actionable interventions to improve nursing care delivery, and ultimately health care, for Alabamians.

The Effect of Numbered Jerseys on Directed Commands, Teamwork, and Clinical Performance During Simulated Emergencies Communication and teamwork are essential during inpatient emergencies such as cardiac arrest and rapid response (RR) codes. We investigated whether wearing numbered jerseys affect directed commands, teamwork, and performance during simulated codes. Eight teams of 6 residents participated in 64 simulations. Four teams were randomized to the experimental group wearing numbered jerseys, and four to the control group wearing work attire. The experimental group used more directed commands (49% vs. 31%, p < .001) and had higher teamwork score (25 vs. 18, p < .001) compared with control group. There was no difference in time to initiation of chest compression, bag-valve-mask ventilation, and correct medications. Time to defibrillation was longer in the experimental group (190 vs. 140 seconds, p = .035). Using numbered jerseys during simulations was associated with increased use of directed commands and better teamwork. Time to performance of clinical actions was similar except for longer time to defibrillation in the jersey group.

Lean in Healthcare: Time for Evolution or Revolution? Lean has gained recognition in healthcare as a quality improvement tool. The purpose of this research was to examine the extent to which quality improvement projects in healthcare adhered to Lean's eight-step process. We analyzed 605 publications identified through a systematic literature review following PRISMA guidelines. Each publication was coded using a structured coding sheet. The most frequent type of publication reported empirical research (48.6%) and most of these (80.3%) shared the results of the Lean projects. Of the 237 publications reporting Lean projects, more than half (71.3%) used an experimental, one-site, pre/postdesign. The impact of the project was most often measured using a single metric (59.1%) that was operational (e.g., waiting time). Although most Lean project publications reported the use of tools to "break down the problem" (84.4%, Step 2) and "see countermeasures through" (70.0%, Step 6), fewer than half described using tools associated with each of the other steps. Projects completed an average of 2.77 steps and none of the projects completed all steps. Although some may perceive low adherence to the tenets of Lean as a deficiency, it may be that Lean approaches are evolving to better meet the needs of healthcare.

Improving Utilization of Vaccine Two-Dimensional (2D) Barcode Scanning Technology Maximizes Accuracy Benefits Background: Recording vaccine data accurately can be problematic in medical documentation, including blank and inaccurate records. Vaccine two-dimensional (2D) barcode scanning has shown promise, yet scanner use to record vaccine data is limited. We sought to identify strategies to improve scanning rates and assess changes in accuracy. Methods: Between January and June 2017, 27 pilot sites within a large health system were assigned to one of four groups to test strategies to maximize scanner use: training only, commitment card, scanning report, or combination. Seventy-two thousand vaccine records were assessed for completeness, accuracy, and scanning. Results: Significant increases in vaccinator scanning rates found with commitment card and scanning report inclusion (alone and paired) compared with the training-only group. Record completeness and accuracy significantly improved with use of scanning. When manually entered, about 1 in 9 records had a missing or inaccurate expiration date; when scanned, this dropped to 1 in 5,000. Conclusions: Pilot findings indicate 2D scanning has the potential to eliminate most omissions and inaccuracies in vaccine records. Such data are critical during a recall or need to trace specific vaccines or patients. Implications: Consistent use and expanded adoption of 2D scanning can meaningfully improve the quality of vaccine records and clinical practices.

Improving Inpatient Tobacco Treatment Measures: Outcomes Through Standardized Treatment, Care Coordination, and Electronic Health Record Optimization Introduction: The Centers for Disease Control and Prevention states that tobacco use is the largest and most preventable cause of disease and mortality in the United States. The Joint Commission implemented inpatient tobacco treatment measures (TTMs) in 2012 to encourage healthcare systems to create processes that help patients quit tobacco use through evidence-based care. Methods: A tobacco cessation care delivery system was implemented at James A. Haley Veterans' Hospital and Clinics, which included: standardized pathways within the Veterans Health Administration (VHA) electronic health record system to improve nicotine replacement therapy ordering; evidence-based tobacco cessation counseling; and improved care coordination for tobacco cessation treatment through the use of technological innovation. Results: Outcomes were obtained from the VHA quality metric reporting system known as Strategic Analytics for Improvement and Learning (SAIL). TOB-2 and TOB-3 (two Joint Commission inpatient TTMs) equivalent to tob20 and tob40 within SAIL improved by greater than 300% after implementation at James A. Haley Veterans' Hospital and Clinics. Conclusion: Implementation of a tobacco cessation care system at James A. Haley Veterans' Hospital and Clinics enhanced interdisciplinary coordination of tobacco cessation care and resulted in improvements of The Joint Commission inpatient TTMs by greater than threefold.

Continuous Cloud-Based Early Warning Score Surveillance to Improve the Safety of Acutely Ill Hospitalized Patients Introduction: This study sought to evaluate the impact of changes made to the process of continually screening hospitalized patients for decompensation. Methods: Patients admitted to hospital wards were screened using a cloud-based early warning score (modified National Early Warning Score [mNEWS]). Patient with mNEWS ≥7 triggered a structured response. Outcomes of this quality improvement study during the intervention period from February through August 2018 (1741 patients) were compared with a control population (1,610 patients) during the same months of 2017. Results: The intervention group improved the time to the first lactate order within 24 hours of mNEWS ≥7 (p < .001), the primary outcome, compared with the control group. There was no significant improvement in time to intensive care unit (ICU) transfer, ICU length of stay (LOS), or hospital mortality. Among patients with a lactate ordered within 24 hours, there was a 47% reduction of in-hospital mortality (odds ratio 0.53, 95% confidence interval 0.3–0.89, p = .02) and a 4.7 day reduction in hospital LOS (p < .001) for intervention versus control cohorts. Conclusions: Cloud-based electronic surveillance can result in earlier detection of clinical decompensation. This intervention resulted in lower hospital LOS and mortality among patients with early detection of and intervention for clinical decompensation.

Assessing the Efficacy of Certificate of Need Laws Through Total Joint Arthroplasty Lawmakers suggest Certificate of Need (CON) laws' main goals are increasing access to healthcare, increasing quality of healthcare, and decreasing healthcare costs. This retrospective database study aims to evaluate the effectiveness of CON through analysis of total knee, hip, and shoulder arthroplasty (TKA, THA, and TSA, respectively). A review was performed using the Humana Insurance PearlDiver national database from 2007 to 2015. Access to care was approximated by the rates of total joint arthroplasty (TJA) in patients diagnosed with arthritis to the corresponding joint. The quality of care was assessed using complication rates after TJA. The total cost of TJA was approximated from average reimbursement to the healthcare facility per procedure. Patients in states without CON programs received TKA, THA, and TSA more frequently (p < .0001, p = .250, p = .019). No significant difference was found in studied complication rates between CON and non-CON states. Similarly, there was no trend found when comparing the cost of each procedure in CON versus non-CON states. These findings are consistent with other recent studies detailing the impact of CON regulation on THA and TKA. The apparent nonsuperiority of CON states in achieving their purported goals may call into question the effectiveness of additional bureaucracy and regulation, suggesting a need for further examination.

Multi-Level Predictors of Discharges Against Medical Advice: Identifying Contributors to Variation Using an All-Payer Database There is increasing evidence of the role of non–patient-level factors on discharge against medical advice (DAMA), but limited quantitative information regarding the extent of their impact. This study quantifies the contribution of discharge-level and hospital-level factors to the variation in DAMA. We grouped variables from the 2014 National Inpatient Sample data and ran incremental mixed-effects logit models with grouping at the level of the discharge, the hospital, and the census region. We obtained the intraclass correlation coefficients (ICCs), and evaluated the incremental change in ICC. The final sample included 2,687,430 discharges. 12.8% of the identified variation in the probability of DAMA was associated with the hospital, and 1.2% of the variation was associated with the census division in which the hospital was located. The final, fully-adjusted model had 7.3% of variation in DAMA associated with the hospital-level, with the greatest percentage reductions because of the addition of patient demographics. Even after adjusting for measured patient-level characteristics, there was a contribution of non–patient-level factors to DAMA outcomes. The findings identify a role for a multi-level approach to addressing DAMA.

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Research in Homoeopathy

Are homoeopathic drugs being used for the treatment of COVID-19 patients, a kind of repurposing? Anil Khurana Indian Journal of Research in Homoeopathy 2020 14(4):231-232

Calendula mother tincture vs normal saline for ulcer dressing as an add-on to Individualized Homoeopathic Intervention in the management of Diabetic Foot Ulcer: A Randomized Controlled Pilot Study Hima Bindu Ponnam, Chetna Deep Lamba, Praveen Oberai, Syed Viquar Masood, Suryanarayana Yandamuri, M Narsing Rao, Raj Kumar Manchanda Indian Journal of Research in Homoeopathy 2020 14(4):233-241 Background: Despite standard management, healing rate of Diabetic Foot Ulcers (DFUs) remains low, posing risk of lower extremity amputation. Objectives: This study was undertaken to evaluate if Calendula Q has added benefit over individualized homoeopathic intervention (IHI). The primary objective was to achieve complete epithelialisation within 20 weeks and secondary objective was to assess the changes in quality of life using DFU Scale-short form (DFU-SF) questionnaire. Materials and Methods: A randomised controlled pilot study with a 20-week intervention was conducted from 2014-2017. 277 cases were screened and 60 cases were enrolled and randomised to Group I: IHI + Calendula Q dressing (n= 30) and Group II: IHI + normal saline (NS) dressing (n = 30), along with standard conventional medication for glycaemic control. Results: The mean time (Group I= 12 weeks, Group II= 11 weeks) of ulcer healing in both groups showed no statistically significant difference, thus calendula Q used for dressing did not have any added benefits (p= 0.0521). Arsenicum album (n= 14, 23.3%), Lycopodium (n= 8, 13.3%), Silicea (n= 7, 11.7%), Sulphur (n= 6, 10%), Phosphorus (n= 5, 10%) and Sepia (n=5, 10%) were found to be effective medicines. Conclusion: IHI, along with wound hygiene and conventional diabetic management, proved to be effective, irrespective of whether Calendula Q or normal saline was used for wound hygiene, thus leading to early, complete epithelialisation of Wagner's first and second stages of DFUs. Further studies comparing IHI with standard care are warranted.

Homoeopathic therapy in cervical spondylosis pain management: A randomised, double-blind, placebo-controlled trial Jaya Gupta, Ramesh Bawaskar, Prakash Rao, Ashish Shivadikar, Paul Sumithran, Ramendra Pal, Shahid Ali, Hima Bindu, MD Arya, Chetna Deep Lamba, Arvind Kumar, Dimpi Kulshreshtha Indian Journal of Research in Homoeopathy 2020 14(4):242-250 Background: Homoeopathic medicines are known to be effective in alleviating pain and other troublesome symptoms of patients suffering from cervical spondylosis. Objective: The primary objective was to evaluate the effectiveness of predefined homoeopathic medicines in the pain management of cervical spondylosis using the Cervical Spondylosis Pain Management Scale (CSPMS). Methods: A prospective, double-blind randomised placebo-controlled multicentric clinical trial was conducted from April 2012 to May 2013. Results: Sixty-seven cases were enrolled in the Homoeopathy group and 69 in the placebo group. One hundred and thirty-four cases that completed the follow-ups were analysed. The improvement in pain was 56.18% in the Homoeopathy group and 46.45% in the placebo group, as per CSPMS. The mean improvement between the groups was not significant: 60.36% in the Homoeopathy group and 48.66% in the placebo group. The mean score of quality of life, assessed using the 'Patient's Global Impression of Change Scale,' was 2.29 ± 1.90 quality of life in the Homoeopathy group and 2.93 ± 2.28 in the placebo group. There was 27.95% more improvement in the Homoeopathy group, as compared to the placebo group. Among the most used medicines were Rhus toxicodendron (n = 19) 28.8%, Calcarea carbonica (n = 7) 10.6%, Kalmia latifolia (n = 7) 10.6% and Paris quadrifolia (n = 8) 12.1%. Conclusion: Homoeopathic medicines are effective in management of acute pain due to cervical spondylosis.

Understanding the role of homoeopathic preparation of Berberis vulgaris in mitigation of sodium oxalate- induced hyperoxaluria: An experimental approach Bhavani Tamilarasan, Porkodi Karthikeyan, Pugazhendhi Kannan, Kalaiselvi Periandavan, Raj K Manchanda, Anil Khurana, Debadatta Nayak, Shanthi Palainivelu Indian Journal of Research in Homoeopathy 2020 14(4):251-259 Background: Hyperoxaluria and calcium oxalate crystal deposition in the kidneys lead to overproduction of reactive oxygen species, resulting in the development of oxidative stress and renal injury. At the cellular levels, mitochondria and NADPH oxidase involved in reactive oxygen species production play a crucial role in the pathogenesis of hyperoxaluria-induced renal injury. Objective: The objective was to investigate the therapeutical effect of homoeopathic drug Berberis vulgaris, a potent antioxidant, upon regulation of NADPH oxidase against acute high-grade sodium oxalate-induced hyperoxaluria in rats. Materials and Methods: Hyperoxaluria was induced in male Wistar rats by administering a single dose of sodium oxalate (70 mg/kg body weight) intraperitoneally, and the treatment groups were pre-treated with homoeopathic drug Berberis vulgaris 6c (20 μl/100 g of body weight) ultra low dose for 7 days. Results: Berberis vulgaris significantly reduces hyperoxaluria-induced oxidative stress and restores antioxidant enzyme activities in kidney tissue. Histological analysis depicted that Berberis vulgaris treatment decreases renal epithelial damage and inflammation and restored normal glomerular morphology. Furthermore, immunoblotting analyses of NADPH oxidase revealed significant increased activity in the renal tissue of hyperoxaluric rats when compared to that of control rats. This has been brought back to normal by Berberis vulgaris treatment. Conclusion: Thus, our results emphasised that the Homoeopathy drug Berberis vulgaris has been effective in ameliorating sodium oxalate-induced acute hyperoxaluria in Wistar rats by modulating mitochondrial oxidative stress through the inhibition of NADPH oxidase.

Pharmacognostical studies of Smilax aspera Linn. – A herbal drug Satish Patel, B Biswas, K Rambabu, EN Sundaram, Renu Arya Indian Journal of Research in Homoeopathy 2020 14(4):260-266 Background: Smilax aspera L. (sarsaparilla or prickly ivy) is a perennial climber from the family Smilacaceae. Its root and rhizome are used as alterative, demulcent, depurative, diaphoretic, diuretic, stimulant and tonic. Objective: To perform standardization of root and rhizome of S. aspera for authentication and identification of raw drug by pharmacognostical, physiochemical, powder and finish product evaluation. Materials and Methods: Air-dried rhizome and roots were boiled, sectioned and stained for macroscopical and microscopical analysis. For physicochemical studies, rhizome and roots were coarsely powdered and subjected for determination of extractive values, ash values, chemical constituents, weight per millilitre, alcohol content, total solids and loss on drying. Finished product analyses (chromatographic studies, sediments, pH and total solid) were also undertaken. Results: The root was longitudinally wrinkled, about 3 mm in diameter with numerous branching, rootless, tough and flexible. Cortex consisted of 18–20 rows of parenchymatous cells; xylem and phloem were arranged in a radiate manner. Rhizome was wrinkled, hard and brown externally and white or light-yellow internally. The outer cortex consisted of polygonal parenchymatous cells. The findings of physicochemical determination of raw drugs including maximum extractive values in alcohol were 5.67% w/w, 0.1% w/w foreign matter, 8.90% w/w moisture content, 10.60% w/w total ash, etc., and finished product parameter showed pH near to 7, total solid 1.07% w/v and 50% v/v alcohol content. Conclusion: The data represented in this article may be used as distinctive diagnostic characters for proper identification, authentication of raw drug to ensure purity, quality and efficacy of drug S. aspera.

Homoeopathic treatment of chronic urticaria – A case series Padmalaya Rath, Parul Indian Journal of Research in Homoeopathy 2020 14(4):267-278 Introduction: Urticaria is a kind of skin complaint with red, raised and itchy bumps. Urticaria frequently occurs after an infection or as a result of an allergic response to some medication, insect bites or food. Psychological stress, exposure to cold or vibration may also trigger urticaria. Urticaria occurs with a lifetime prevalence of around 20%. In around 30% patients of urticaria, attacks often recur for months or years. Cases summary: This is a case series of five patients suffering from chronic urticaria having erythematous lesions, intense itching, redness and swelling treated at the Dermatology outpatient department of Dr D. P. Rastogi Central Research Institute for Homoeopathy, Noida, Uttar Pradesh, India. The patients were prescribed indicated constitutional Homoeopathic medicines. Changes in haematological and serological tests, Measure Yourself Medical Outcome Profile 2 and Urticaria Activity Score summed over 7 days at baseline and at the end of treatment showed reasonable improvement in disease as well as in the quality of life. Homoeopathic medicines such as Apis mellifica, Calcarea carbonica, Rumex crispus, Pulsatilla and Histamine were found useful.

Homoeopathic treatment of viral warts with Calcarea phosphorica Nidhi Mahajan, Ashish Mahajan, Aditi Bhinda, Sapna Salodiya Indian Journal of Research in Homoeopathy 2020 14(4):279-286 Introduction: Viral warts are the most common cutaneous infection caused by human papillomavirus. Warts can be treated by many available modalities such as cryotherapy, chemical cauterization, curettage, electrodessication and laser removal. However, most of these therapies can cause scarring. They also cause application-site reaction and recurrence. The homoeopathic literature has a plethora of medicines for the treatment of warts. Case Summary: A 4-year-old girl presented with reappearance of multiple warts on the face after a month of laser treatment. This time, the warts were on the right side of the forehead and one on the right cheek and were persisting for 8 months. The patient responded well to individualised homoeopathic treatment, i.e. Calcarea phosphorica 200 in single dose with complete recovery within 1 month without subsequent relapse. Even though the medicine is mentioned in the fourth grade against the rubric 'Face – Warts' in the Complete Repertory and is not used commonly in the cases of warts, it acted beneficially. Hence, this case emphasises the importance of individualised homoeopathic treatment based on characteristic general symptoms.

Pelvic inflammatory disease treated with homoeopathic medicine Calcarea carbonica: A case Report Swati Pandey, Raj K Pandit Indian Journal of Research in Homoeopathy 2020 14(4):287-292 Introduction: Pelvic Inflammatory Disease (PID) is a polymicrobial infection of the upper genital tract characterised clinically by triad of symptoms and signs: pelvic pain, cervical motion with adnexal tenderness and fever. Conventional treatment is with broad-spectrum antibiotics. The alternative medicine, especially Homoeopathy, is the second choice of therapy as per the WHO. Case reports of PID in the medical literature are scant. We aim to report a case treated with homoeopathic constitutional medicine in a woman suffering from PID. Case Summary: A 29-year-old female presented with the symptoms of white discharge per vagina, constant dull pain in the lower abdomen, low backache, fever and lassitude for 2 weeks. Clinical findings and ultrasound of the whole abdomen suggested PID. Individualised homoeopathic medicine Calcarea carbonica was prescribed in centesimal potency which showed a positive role in the treatment of PID. Causal attribution of changes in her condition to the homoeopathic treatment was depicted by modified Naranjo criteria. Future observational studies and randomised control trials are suggested to ascertain the efficacy of homoeopathy in the cases of PID.

Large-scale homoeoprophylaxis as an add-on measure to prevent COVID-19 disease: Cuban preliminary experiences Johann Perdomo Delgado, Antonio Emilio Vallin Garcia, Evelyn Anie Gonzalez Pla, Lissette Aguila Peña, Diadelis De La Caridad Remirez Figueredo, Alberto Inocente Hernandez Rodriguez, Magaly Victoria Carrero Figueroa, Concepcion Campa Huergo Indian Journal of Research in Homoeopathy 2020 14(4):293-294

Lessons learnt from the Spanish Flu pandemic Karanpreet H Nahar Indian Journal of Research in Homoeopathy 2020 14(4):295-296

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Radiation and Cancer Research

DNA-Dependent protein kinase in DNA damage response: Three decades and beyond Yoshihisa Matsumoto, Mukesh Kumar Sharma Journal of Radiation and Cancer Research 2020 11(4):123-134 Ionizing radiation exerts various biological effects, including cell killing and carcinogenesis, mainly through generating damage on DNA. Among various types of DNA damage, DNA double-strand break (DSB) is considered the most deleterious and most intimately related to biolog?ical effects of radiation. DNA-dependent protein kinase (DNA-PK), consisting of DNA-PK catalytic subunit and Ku80-Ku70 heterodimer (Ku), is activated upon binding to the end of double-stranded DNA and acts as the molecular sensor for DSB. While DSB is repaired mainly through homologous recombination and nonhomologous end joining in eukaryotes, DNA-PK is shown to be essential in the latter pathway. Moreover, DNA-PK is reported to be capable of phosphorylating a number of proteins, suggesting versatile functions of DNA-PK in cellular response to DSB. Here, we review the advance in our understanding on DNA-PK in three decades and remaining problems.

An approach to cancer amid COVID-19 pandemic – Radiation oncologists perspective Shaqul Qamar Wani, Talib Khan, Fir Afroz Journal of Radiation and Cancer Research 2020 11(4):135-139 The background of this article is to provide a general information regarding the safety of the patients and health-care workers besides providing management guidelines for cancer patients in the current context of COVID 19 (SARS CoV-2) crisis. The treatment recommendations are prioritized as per the risk stratification till the current crisis is mitigated. The recommendations not only provides information in dealing with different malignancies treated either with curative or palliative intent but also ascertains the role of electronic media as an effective source of communication with patients whether on active or pending treatment or on follow-up, so that their anxiety levels and mental fears regarding their disease and future management plans amid COVID-19 pandemic are minimised.

The tubarial glands: Discovered but not defined – A narrative review Tarun Kumar Suvvari, Nithya Arigapudi Journal of Radiation and Cancer Research 2020 11(4):140-141 A pair of salivary glands, named as tubarial glands, was found between the nasal cavity and throat, i.e., at the nasopharynx's lateral walls, overlaying the torus tubarius by the Netherlands Cancer Institute while working on radiation toxicity among prostate cancer patients. The tubarial glands were identified using prostate-specific membrane antigen imaging using positron emission tomography coupled with computed tomography, which is used to detect the spread of prostate cancer. The anatomy, physiology, oncological study of the glands, and data's interpretation and limitations from the research to date have been discussed.

Complexity of chromosomal aberrations and gene expression changes in human blood lymphocytes after exposure to alpha particle radiation Karthik Kanagaraj, Vasumathy Rajan, Badri N Pandey, Perumal Venkatachalam Journal of Radiation and Cancer Research 2020 11(4):142-149 Background: Targeted alpha therapy (TAT) is emerging as an effective treatment modality of cancer especially for micrometastasis, lymphoproliferative malignancies, and palliative approaches of bone cancer. Human blood lymphocytes may encounter alpha (a) exposure while traversal of targeted a particle emitting radio isotopes to the tumor site, due to their nonspecificity and release of radio isotopes from the legends used for targeting. Such radiation effects to lymphocytes may be implicated in short and long term health effects during TAT. Aims and Objectives: To see the effects of a-particle in blood lymphocytes and to compare their complexity of aberration with both and X-rays. Materials and Methods: Chromosomal aberrations such as dicentric chromosome, micronuclei, nucleoplasmic bridge (NPB) in the peripheral blood lymphocytes were scored for both a alpha particle and X rays. Then, the chromosome aberrations (CA) frequency was correlated with the gene expression (FDXR, CDKN1A and GADD45A) to both the type of radiations. Results: CA induced by a radiation was complex and highly dispersed when compared to low LET radiation. Moreover, magnitude of NPB was significantly higher in case of a radiation than radiation. A dose dependent increase in gene expression (FDXR, CDKN1A and GADD45) was observed after a radiation, which however, was higher in case of a radiation than X rays. Conclusion: These results provide better understanding about effects of a radiation on human lymphocytes, which may be significant implications in developing better TAT strategies for cancer.

Activation of epidermal growth factor receptor/insulin-like growth factor 1 receptor-β-Catenin-CD44 pathway in periampullary cancer Biswabandhu Bankura, Suvendu Maji, Balarko Chakraborty, Neyaz Alam, Chinmay Kumar Panda Journal of Radiation and Cancer Research 2020 11(4):150-156 Background: Periampullary cancer (PC) is a global medical burden. Less than 5% of patients experience an overall survival of 5 years or more. The study aims to analyze the importance of epidermal growth factor receptor (EGFR)/insulin-like growth factor 1 receptor (IGF1R)–beta-catenin (β-catenin)–CD44 pathway in the development of periampullary cancer of Indian patients. Subjects and Methods: Expression profile of EGFR, IGF1R, β-catenin, and CD44 was verified by immunohistochemical analysis in primary tumor samples (N = 14) and respective adjacent normal tissues. Results: In periampullary carcinoma patients, a high level of EGFR expression was seen in 64% of the samples along with co-expression of IGF1R in 77.8% of samples. Furthermore, the high expression of EGFR and IGF1R significantly correlated with the increased expression of β-catenin along with CD44 expression of the tumors. Conclusion: The EGFR/IGF1R–β-catenin–CD44 pathway seems to be important in the development of PC with clinical importance.

Clinical and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status correlation study in breast cancer patients: An experience from a tertiary care center Rashmi Singh, Anup Kumar, Rajanigandha Tudu, Praveer Kumar Singh Munda Journal of Radiation and Cancer Research 2020 11(4):157-160 Background: Breast cancer is usually a systemic disease with outcomes dependent on various factors. We present here our departmental retrospective data of 74 breast cancer patients treated between January 2016 and October 2017, with a focus on various prognostic and predictive factors. Materials and Methods: Patients' details were retrieved from departmental case records regarding age, menopausal status, tumor size (T), axillary lymph node status (N), grade, and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (Her2) status. Using SPSS software version 20.0, cross-tabulation, the Chi-square test, and Spearman correlation were applied where appropriate. Results: The median age of patients was 48.75 ± 11.08 years with more patients in premenopausal age (54.1%). Stage III was the most common presentation (66.2%). In addition, Grade 3 in tumor was most common (51.4%). ER(+), PR(+), and Her2(+) cases were 58.1%, 52.7%, and 28.4%, respectively. Nearly 29.7% of patients were triple negative. Grade of the tumor correlated significantly with tumor size and lymph node staging (P = 0.002). In addition, ER and PR expression was correlated with each other (P = 0.000). Conclusions: Advanced stage, higher tumor grade, and high prevalence of Triple-negative breast cancer in our patients are poor prognostic and predictive factors. Higher tumor grade is correlated with increased T and N staging, and tumor ER and PR expressions were correlated with each other.

DNA damage and survival in bystander human intestinal cells treated with conditioned medium from tritium-labeled cells Manjoor Ali, Vasumathy Rajan, Badri Narain Pandey Journal of Radiation and Cancer Research 2020 11(4):161-166 Background: Tritium exposure could be one of the radiation hazards in case of accidental exposure with intestine as one of the major target organs. In the cells, low-energy beta emitted from tritium would traverse a very short distance (a few microns). Hence, the intestinal epithelial cells with nuclear localization of tritium would exert its radiobiological effect also through bystander mechanism. In the present study, the effect of conditioned medium obtained from tritiated thymidine-labeled human normal intestinal epithelial (INT407) cells was studied on respective bystander cells in terms of magnitude of survival and induction of DNA damage. Materials and Methods: The survival and proliferation of bystander INT407 cells treated with control/irradiated conditioned medium were studied using clonogenic and 5-bromo-2-deoxyuridine (BrdU)-labeling assays. The magnitude of DNA double-strand break was measured by immunofluorescence of η-H2AX by confocal microscopy. Intracellular nitric oxide (NO) in these cells was measured using 4,5-diaminofluorescein diacetate fluorescent dye. Results: Bystander cells treated with conditioned medium from tritiated thymidine-labeled cells showed increased clonogenic survival and BrdU labeling. Cells labeled with tritiated thymidine showed attenuation of η-H2AX foci at longer period (24 and 48 h) of labeling than at 15 h. Moreover, the bystander cells treated with irradiated conditioned medium showed a higher magnitude of η-H2AX foci at 24 h. However, compared to 24 h, 48-h treatment of irradiated conditioned medium resulted in a decrease in η-H2AX foci in the bystander cells. Increased level of intracellular NO was observed in the bystander cells treated with irradiated conditioned medium. Conclusions: Bystander cells treated with conditioned medium obtained from tritiated thymidine-labeled cells showed increased clonogenic survival and proliferation, which was correlated with an increase in DNA double-strand break and NO production in these cells.

Management and outcome of extraosseous ewing's sarcoma family tumors treated at a tertiary care center in North East India: A retrospective analysis Mouchumee Bhattacharyya, Partha Pratim Medhi, Apurba K Kalita, Faridha Jane R M Momin, Subhalakshmi Saikia, Manoj Kalita, Rakesh Mishra, Ghritashee Bora, Shashank Bansal Journal of Radiation and Cancer Research 2020 11(4):167-173 Introduction: Extraosseous Ewing's Sarcoma is rare, aggressive malignant soft-tissue tumors treated similar to Ewing's sarcoma of bone. This study evaluates the clinicopathological pattern, treatment and outcomes of localized extraosseous Ewing's sarcoma family tumors (ESFTs) treated with an uniform treatment regimen. Materials and Methods: This is a retrospective single institution study where we evaluated the hospital records of localized extraosseous ESFT treated between January 2011 and December 2018. Fifteen patients were found eligible for analysis. Patient demographics, management details, and outcomes were analyzed statistically. Time to event was measured from the date of diagnosis and survival curves were estimated by Kaplan–Meier method with Log-rank test for comparison. Results: The median follow-up of the cohort was 17 months (range: 3–81 months). The mean age of patients was 14.4 years and the average tumor size was 9.92 cm. Two-thirds of the patients received definitive radiotherapy as the local treatment with 93.3% patients receiving induction chemotherapy. The 5-year local control rate, progression-free survival, and overall survival (OS) were 80%, 53.3%, and 46.7%, respectively. On univariate analysis, tumor size <8 cm and good response to chemotherapy were associated with significantly improved OS (P = 0.049 and 0.04, respectively), while local control rates were better for patients receiving radiotherapy dose 54 Gray and above (P = 0.044). Conclusion: The optimum management of extraosseous ESFT consists of multimodality therapy with multidrug chemotherapy, surgery, and radiotherapy. Localized tumors of <8 cm size with favorable response to induction chemotherapy have the best prognosis.

Carcinoma glottis with parotid metastasis U Suryanarayan, Shah Aastha Ashokkumar, Isha Shah, Rajal Shah Journal of Radiation and Cancer Research 2020 11(4):174-177 Introduction: Glottic carcinomas represent approximately one third of the laryngeal cancers. True glottis includes both true vocal cords including anterior and posterior commissures. True vocal cord are as such devoid of lymphatics, so the chances of lymph node metastasis as such is very low. The chances of distant metastasis is also very rare. Herein we report a case of glottic cancer metastasising to parotid gland. Case report: A sixty eight year old male non smoker reported to our department with complaint of change of voice since three months. On computed tomography scan of head and neck, soft tissue thickness of about seven millimeter was seen over right true and false vocal cord and 2.3 * 1.9 cm lesion was seen involving the left lobe of the parotid gland. MRI of neck and paranasal sinuses was performed immediately following tomography which showed 2.6*1.9*3.1 cm lesion was seen involving deep lobe of left parotid gland which appeared isointense on T1w, hyperintense on T2w, not suppressed on STIR. There was no any evidence of capsular breach. Seven millimeter thickness was seen over right true and false vocal cord. These findings were further confirmed by direct laryngoscopic examination which showed mucosal irregularity over right true and false vocal cord with normal mobility of both vocal cords and punch biopsy was taken from it which came out to be well differentiated squamous cell carcinoma. Ultrasonography guided biopsy was taken from the deep lobe of the left parotid gland which came out to be metastatic squamous cell carcinoma. Patient was offered curative radiotherapy to a dose of 55 Gy in 20 fractions and the parotid lesion was addressed by parotidectomy, which showed no evidence of malignancy which might be considered to be an abscopal effect. Conclusion: The involvement of the parotid gland in case of glottic cancer is a very rare occurrence.

Dosimetric evaluation of hippocampus incidental radiation dose in nasopharyngeal cancer patients treated with intensity-modulated radiotherapy Tony Jacob, Donald Fernandes, MS Athiyamaan, B Sandesh Rao, Sharaschandra Shankar, MS Vidyasagar, V Mohsina Journal of Radiation and Cancer Research 2020 11(4):178-182 Background: The incidental radiation exposure to hippocampus during radiation therapy for nasopharyngeal cancers may contribute to short-term toxicity like disequilibrium and lack of inhibition and also to long-term memory loss. Objective: To diametrically evaluate the dose received by hippocampus in patients with nasopharyngeal cancer undergoing intensity-modulated radiotherapy (IMRT). Materials and Methods: Eleven patients with histologically proven locally advanced nasopharyngeal squamous cell carcinoma were retrospectively analyzed in this study. The total prescribed dose to the planning target volume was 70 Gy (D95%) delivered in 2 Gy daily fractions using IMRT technique. Employing the anatomical guidelines and magnetic resonance imaging coregistration, the hippocampi were delineated on axial imaging from the simulation computed tomography scan for each patient. IMRT treatment plans were generated without applying dose–volume constraints to the hippocampus. Maximum hippocampus dose, mean hippocampus dose, minimum hippocampus dose, and hippocampus volume receiving 3 Gray dose (V3Gy) were analyzed. Results: The mean hippocampus volume was 4.7 cm3. The average minimum dose to the entire hippocampus was 5.276 Gy (range, 0.072–18.609 Gy); the average maximum point dose to the hippocampus was 21.405 Gy (range, 0.595–59.832 Gy); and the average mean dose to the entire hippocampus volume was 10.922 Gy (range, 0.194–34.706 Gy) and V3Gy was 79.15 Gy (range, 0%–100%). Conclusion: The dosimetric analysis suggests that patients who underwent IMRT for nasopharyngeal cancer received significantly high incidental dose to the hippocampus. The study creates awareness regarding the need to routinely delineate hippocampus as an organ at risk in the radiotherapy for nasopharyngeal cancers.

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