Paediatric Dermatology

Genetics of Vascular Malformations: Current Perspectives Kin Fon Leong Indian Journal of Paediatric Dermatology 2021 22(1):1-11 For decades, vascular anomalies are categorized as either vascular tumors or malformations based on their onset, clinical course, radiologic, and histologic features. Owing to the heterogeneity of vascular anomalies, they are frequently misdiagnosed. With the advent of massively parallel next-generation sequencing, the molecular landscape of vascular anomalies is rapidly evolving and recent discoveries have shed light on the genetic basis and classification of these vascular disorders. The genotype-phenotype correlation will provide a more precise classification of vascular anomalies and form the basis for future targeted pharmacologic therapy. Thus far, inhibitor of mTOR, AKT1, and PIK3CA (sirolimus, miransertib, and alpelisib) have promising clinical results. In vascular malformations, majority of sporadic cases are due to somatic mutations that disrupt the main endothelial receptor intracellular signaling pathways, i.e., PIK3CA-AKT-mTOR, RAS - MAPK – ERK, and SMAD signaling pathways. Most of the sporadic vascular malformations are caused by somatic mutations that are acquired after fertilization, instead of being inherited from his parents. In general, this type of mosaicism is not inherited, except when the mutation affects the gonads.

Cosmetic Procedures in Adolescents: What's Safe and What Can Wait Indian Journal of Paediatric Dermatology 2021 22(1):12-20 Teenagers between 13 and 19 years are increasingly seeking cosmetic procedures. They are suffering from anxiety, depression, and low self-esteem as a result of an obsession with body image and celebrity culture, fueled by social networking sites. Teenagers seek cosmetic procedures most commonly for traumatic scars, acne and acne scars, pigmentary abnormalities, hypertrichosis, hirsutism, and tattoo removal. They demand plastic surgery for nose deformities, breast asymmetry, ear abnormalities, and congenital deformities. The physical, emotional, psychological, social, ethical, and legal aspects must be considered while counseling adolescents. Not every teenager seeking cosmetic surgery is well suited for a procedure, and teens must demonstrate emotional maturity and an understanding of the limitations of these procedures and the risks involved. There should be a 3-month cooling-off period, followed by another consultation, which should be done in the presence of a parent. Only very essential surgery should be performed, giving realistic expectations on the outcome of procedures, as they rely too much on physical appearance to gain confidence. A psychiatric evaluation is essential to rule out body dysmorphic disorders in those repeatedly seeking treatment for minor defects. Sometimes, procedures are necessary to avoid social withdrawal and loss of self-esteem. Proper informed consent should be taken, explaining the benefits, limitations, and risks involved. Ideally, teenagers should not receive cosmetic or surgical procedures unless there are compelling medical or psychological reasons to do so. A successful aesthetic procedure in a mature teenager can have a positive influence, whereas surgery on an immature, psychologically unstable adolescent can have an adverse impact. This review discusses what is safe and what can wait, still there is limited evidence. There is a strong need for guidelines for the use of cosmetic surgery on children and teenagers.

Role of Elimination Diet in Atopic Dermatitis: Current Evidence and Understanding Indian Journal of Paediatric Dermatology 2021 22(1):21-28 Atopic dermatitis (AD) is a fairly common dermatosis of childhood. In many cases, parents are concerned that food allergy plays a role in their child's symptoms and they ask whether practicing elimination diets would help in controlling the symptoms. In this review, we try to provide concise answers to the questions raised by the parents, apart from addressing the myths associated with elimination diets in AD and provide scientific evidence in favor of or against the common notions. A comprehensive English-language literature search for the role of elimination diet in AD across multiple databases (PubMed, EMBASE, MEDLINE, and Cochrane) for keywords (alone and in combination) was performed. MeSH as well as non-MeSH terms such as “AD,” “diet elimination,” “treatment,” “prevention,” “evidence,” “blanket elimination,” and “specific exclusion diet” were taken into consideration. There is level I evidence to support specific exclusion diets in preselected and screened patients, but there is insufficient evidence to recommend strict (blanket) elimination diets.

Pattern of Dermatoses in Small Children in a Tertiary Care Hospital Indian Journal of Paediatric Dermatology 2021 22(1):29-36 Aims: The aim of the study was to study the pattern of dermatoses in children up to 5 years of age. Settings and Design: It is an observational study done in a tertiary care hospital. Subjects and Methods: A total of 505 patients, aged up to 5 years, attending the department of dermatology, venereology, and leprosy for a duration of 18 months from January 2017 to June 2018 were included in the study. Statistical Analysis Used: All results were statistically analyzed by IBM SPSS software and Chi-square test was used to compare the associations. Results: Preschoolchildren (75.44%) formed the majority. Males (54.65%) outnumbered females. Infections constituted the most (45.94%) followed by eczema (21.98%), hypersensitivity disorders (14.25%), nevi (4.55%), papulosquamous (3.76%), pigmentary (3.76%), physiological and transient noninfective neonatal conditions (3.56%), sweat gland (2.97%), hair disorders (0.59%), and other dermatoses (2.97%). Conclusions: Infections/infestations constituted the most among the dermatoses in children up to 5 years of age. As they are preventable, educating the parents, guardian, care takers, and teachers in the preschool about communicable diseases can limit their transmission and improve the well-being of children.

Clinical Spectrum of Cutaneous Adverse Drug Reactions in Pediatric Population in East Coast of Andhra Pradesh: An Observational Study VV V Satyanarayana, Suruthi Purushothaman, Bonu Chandipriya Indian Journal of Paediatric Dermatology 2021 22(1):37-42 Context: Cutaneous adverse drug reaction (CADR) among pediatric population is underappreciated and often misdiagnosed in clinical settings. Furthermore, epidemiologic data on only cutaneous adverse reactions among this population are limited. Aim: The aim of this study is to analyze the CADRs with reference to the pattern, causative drugs, its subgroup analysis, and other clinical characteristics among children. Settings and Design: This was an observational, hospital-based study over a period of 12 months. Materials and Methods: The CADRs occurring and referred to the inpatient and outpatient department of dermatology were actively monitored and the collected reports were analyzed for CADR pattern, drug groups, clinicodemographic profile, and severity of adverse drug reaction (ADR). Statistical Analysis Used: Data were documented in Microsoft Excel and analyzed using SPSS Version 20.0. Results: A total of 33 CADRs were documented. Most of the ADRs (40%) occurred between the age of 11 and 15 years. Antimicrobials comprised the major group of drugs causing ADRs (42.4%). Maculopapular rash (54.5%) and urticaria (15.2%) were the most common type of ADR. A single case of death due to anticonvulsant-induced toxic epidermal necrolysis had been observed in the study period. There were more occurrences of ADRs with multiple drugs compared to single-drug therapy. About 80% of reactions were of mild to moderate. Conclusion: Knowledge of the pattern and the offending drug helps in better diagnosis, management, reduced complications in this population, and also helps in preventing recurrences, thereby helps in promoting the safe use of drugs, which can overall impact the quality of health care among children positively.

Acne Fulminans: A Case Report and Review of Literature Indian Journal of Paediatric Dermatology 2021 22(1):43-47 Acne fulminans (AF), a variant of acne vulgaris, is a rare disease that occurs after treatment of AF with oral isotretinoin. Less than 200 cases of AF have been reported in literature, mostly in young men and all with varying clinical presentations. A thorough search of literature was performed for AF using PubMed, MEDLINE, EMBASE, and UK PubMed Central electronic databases. Pathogenesis is not clearly established. However, it is most likely due to hypersensitivity reactions to sebum or bacterial antigens. It presents as sudden eruption of friable, hemorrhagic crusting overlying the ulcers, plaques, and tender nodules, usually on the trunk, with or without systemic symptoms such as malaise, fever, and arthralgia a few days after initiation of oral isotretinoin therapy. Laboratory abnormalities including raised erythrocyte sedimentation rate, altered hematological profile, and radiological evidence of osteolytic bone lesions may be found. Treatment involves the use of oral steroids with subsequent addition of oral isotretinoin. Many other immunosuppressive therapies have been tried.

Clinical and Dermoscopic Spectrum: Novel Findings in Interesting Cases Indian Journal of Paediatric Dermatology 2021 22(1):48-51 Uncommon, interesting clinical entities presenting in dermatological practice often challenges the diagnostic skills of a trained dermatologist. A non-invasive tool for recognition of these conditions is especially relevant in the paediatric population and dermoscopy plays a pivotal role in diagnosing these cases. A spectrum of novel clinical and dermoscopic findings is reported in four interesting cases. (vitiligo ponctue, cutaneous larva migrans, zosteriform angiokeratoma, linear milia en plaque).

Norwegian (Crusted) Scabies Involving Eyelids and Conjunctiva Indian Journal of Paediatric Dermatology 2021 22(1):52-55 Scabies is a parasitosis caused by the mite sarcoptes scabiei var. hominis, with crusted scabies being more contagious than classic scabies because of a larger mite burden. It can lead to an epidemic of classic scabies if not diagnosed early and treated accordingly. We report a 10-year-old boy who presented with a complaint of an inability to open his left eye and irritation in the right eye. Examination showed the presence of multiple crusted lesions throughout the body, including face and eyelids, and a yellowish patch in the right bulbar conjunctiva. The histopathological evaluation of the specimen of the conjunctival lesion confirmed it to be sarcoptes infestation. Face and eyelids involvement are very rarely in crusted scabies and only a few cases have been reported in the past. Our report demonstrates conjunctiva as an unusual site of involvement in these cases.

Localized Pseudoxanthomatous Mastocytosis of Vulva Indian Journal of Paediatric Dermatology 2021 22(1):56-58 Cutaneous mastocytosis (CM) is a mast cell proliferative disorder that is common in the pediatric age group. Common entities are urticaria pigmentosa, solitary mastocytoma, telangiectasia macularis eruptive perstans. and diffuse CM. Pseudoxanthomatous mastocytosis presents in the form of yellowish nodular lesion resembling xanthoma and is a rare variant and not reported much in the literature. We, hereby report a rare case of localized vulvar pseudoxanthomatous mastocytosis in a 10-year-old female child.

Curious Subcutaneous Swellings: A Case of Pediatric Myocysticercosis Indian Journal of Paediatric Dermatology 2021 22(1):59-61 Cysticercosis is a parasitic infection caused by the larval stage of the tape worm, Cysticercus cellulosae, chiefly affecting the subcutaneous tissue, central nervous system, orbit, and the skeletal muscles. It occurs in human due to ingestion of contaminated water or raw meat of pig. We hereby present a case of a 6-year-old female presenting with multiple subcutaneous swellings of 3 months' duration, associated with painful movement and associated with a history of on and off fever and malaise. Local part ultrasonography revealed multiple cystic lesions in the muscular plane, with peripheral streak of calcification indicative of scolex. Fine-needle aspiration cytology of the lesions showed revealed degenerated and viable polymorphs, macrophages, few lymphocytes, and foreign body giant cells with foci of necrosis, with occasional hooklets of parasite, with findings suggestive of parasitic infection in neck with acute on chronic inflammation. Computed tomography (CT) scan of brain was normal. Thus, clinical, radiological, and cytological findings confirmed the diagnosis of myocysticercosis. This case is presented because of the rareness of its occurrence.

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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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Dermatology

High prevalence of high-risk cutaneous squamous cell carcinoma in the thrace region of Turkey Sezgi Sarikaya Solak, Haydar Yöndem, Yildiz Gursel Urun, Mert Cezik, Nuray Can Turkish Journal of Dermatology 2020 14(4):83-89 Background: The characteristics of cutaneous squamous cell carcinoma (cSCC) may show differences according to the geographic distribution and ethnicity. Although most cSCCs are treated with surgical excision or other local interventions, high-risk cSCCs may have poor outcome. In the present study, we aimed to evaluate the clinicopathological characteristics and determine the high-risk features of cSCCs in the Thrace region of Turkey where the information on cSCCs is scarce. Methods: We retrospectively investigated the biopsy-proven cSCCs diagnosed between the years 2014 and 2018, in a tertiary university hospital and evaluated the high-risk features. Results: A total of 211 cSCCs were included. Men with cSCC were significantly younger than women with cSCC (P <.001). Almost one-half of the tumors (n = 103) were located on the lower lip. Patients with a cSCC on the lower lip were younger than those with a cSCC on the other sites. All patients with a cSCC on the ears were men. Twenty-eight percent of patients had tumor size more than 20 mm and 28% had tumor thickness more than 6 mm. Immunosuppression was present in 7.6% of patients. A total of 177 (83.9%) patients had high-risk cSCC. The local recurrence rate was 6.2%, and the metastasis rate was 5.2%. Conclusions: The Thrace region has significant number of cSCC, and high-risk features are very frequent. Clinicians should carefully evaluate the cSCCs in terms of high-risk features.

CYP4F22 gene mutations in patients with autosomal recessive congenital ichthyosis: Identification of two novel mutations Esra Arslan Ates, Hüseyin Onay, Ilgen Ertam, Esra Ataman, Filiz Hazan, Asude Durmaz, Tugrul Dereli, Ferda Özkinay Turkish Journal of Dermatology 2020 14(4):90-94 Background: Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous keratinization disorder, which is clinically classified into five main forms: Lamellar ichthyosis, congenital ichthyosiform erythroderma, harlequin ichthyosis, self-healing collodion baby, and bathing suit ichthyosis. Mutations in TGM1, ABCA12, ALOX12B, ALOXE3, NIPAL4, CYP4F22, PNPLA1, LIPN, and CERS3 genes have been described in patients with ARCI. However, in 20% of the ARCI patients, the genetic defect remains unknown. Materials and Methods: In this study, we investigated the mutations in the CYP4F22 gene in ARCI patients who do not have mutations in two common ARCI genes, NIPAL4 and TGM1. Twenty-two patients diagnosed with ARCI and having no mutations in TGM1 and NIPAL4 genes were included in the study. Their CYP4F22 genes were sequenced using the Sanger sequencing method. Results: In 5 of 22 (22.7%) ARCI patients, four different mutations, of which two were previously reported, were found. The two novel mutations were c.976C> T and c.1189C> T. The c.727C> T and c.1303C>T mutations were previously reported. Conclusions: This study expands the CYP4F22 mutation spectrum and to provide more accurate genetic counseling for patients at risk.

Androphenotypic features in patients with coronary artery disease Gülsüm Gençoglan, Fatmagül Gülbaşaran, Işıl Inanir, Uğur Kemal Tezcan, Kamer Gündüz Turkish Journal of Dermatology 2020 14(4):95-98 Objective: It has been a debate whether phenotypic features are associated with increased risk of coronary heart disease. Proposed explanations for this relation include biological aging, individual susceptibilities, and androgens which contribute to both the atherosclerotic process and dermatological signs. The results of the studies are inconsistent and most are not based on cardiovascular imaging techniques. Here, association between androphenotypic features and the risk and severity of coronary artery disease (CAD) in men is evaluated. Methods: This case–control study consists of 166 male patients with angiography-proven CAD and 160 age-gender-matched controls. Gensini score of angiograms (for severity of CAD) and phenotypic characteristics including androgenetic alopecia (AGA), thoracic hairiness (TH), hair graying a diagonal earlobe crease (DEC), and hairy ear (HE) were recorded. Men with well-established cardiovascular risk factors were excluded. Results: AGA, DEC, and HE were significantly more frequent in patients with CAD than controls (98.2% and 83.1% [P < 0.001], 61.4% and 23.8% [P < 0.001], 69.3% and 50.6% [P = 0.001], respectively). As the severity of AGA increased, the incidence of heart disease was increasing in patients. The presence of TH and AGA was found to be related to higher Gensini scores. Conclusion: The exact mechanism between these phenotypic features and CAD still remains to be elucidated. However, observation of visible aging signs is easy and inexpensive. AGA, HE, and DEC may be used as early screening tools for CAD.

Misleading clinical presentation of a palmar lichen nitidus masquerading as pompholyx Ghazal Ahmed, Satyaki Ganguly, Hitesh Yadav Turkish Journal of Dermatology 2020 14(4):99-101 Lichen nitidus is usually a chronic localized disease of unknown etiology having multiple differentials. A 10-year-old boy presented with itchy, multiple, discrete, grouped, and minute papules with surrounding erythema in some and exfoliation in few others, involving the center of the right palm, the palmar aspect of the left little finger with few lesions over the dorsal surface of both the hands. The presenting feature misguided us with a few clinical points which are unusual in lichen nitidus. We report the case to highlight the clinical mimicry and limitations of clinical assessment for diagnosing lichen nitidus.

Psoriasis vulgaris developing in healed pemphigus vulgaris: A rare case of epitope spread or isotopic response? Ravindranath Brahmadeo Chavan, Vasudha A Belgaumkar, Nitika Sanjay Deshmukh, Ranjitha Krishnegowda Turkish Journal of Dermatology 2020 14(4):102-105 Although psoriasis and autoimmune blistering diseases are considered to be disorders with completely different etiopathogenesis, literature has documented a few cases of psoriasis associated with bullous diseases, particularly bullous pemphigoid. Here, we report the case of a 30-year-old male presenting with multiple flaccid blisters and erosions, clinically and histopathologically consistent with the diagnosis of pemphigus vulgaris. Although all these lesions resolved after two doses of dexamethasone cyclophosphamide pulse therapy, he returned 3 weeks later with multiple erythematous scaly plaques developing over the postinflammatory areas, compatible with the diagnosis of psoriasis vulgaris, which necessitated a modification in the treatment protocol. This rare case highlights the diagnostic and therapeutic challenges accompanying this unique scenario and attempts to elucidate the probable pathogenic mechanisms underlying the co-existence (simultaneous or sequential) of these two apparently unrelated dermatoses.

Phacomatosis pigmentokeratotica associated with unilateral toe walking due to short achilles tendon Andac Salman, Ayse Deniz Yucelten, Ozlem Akin Cakici, Olcay Unver Turkish Journal of Dermatology 2020 14(4):106-108 Phacomatosis pigmentokeratotica (PPK) is characterized by the co-occurrence of speckled lentiginous nevus (nevus spilus) and an organoid nevus with or without extracutaneous involvement. The extracutaneous manifestations may vary widely with musculoskeletal, neurologic, ocular, and vascular findings. The PPK is also associated with an increased risk of cutaneous or extracutaneous tumors. Therefore, the patients with PPK should be followed up regularly for possible malignant transformation. Here, we report a 5-year-old boy with PPK associated with toe walking due to short Achilles tendon, which was not previously reported, to our knowledge.

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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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Pulmonology

Chronic obstructive pulmonary disease: A review about gender differences Carolina Santos, Tiago Pereira, Raquel Barros Eurasian Journal of Pulmonology 2020 22(3):135-143 The major risk factor for chronic obstructive pulmonary disease (COPD) is smoking. COPD is thought to be traditionally a male illness, but its prevalence in women is increasing because they are adopting lifestyle habits similar to men. A literature review of publications indexed in MEDLINE, Latindex, SciELO, and DOAJ databases was carried out. Were considered 44 articles with relevance to the topic addressed. The literature review aim was to characterize the gender susceptibility differences in COPD development as well as the changes that this disease may induce in the lung function. Through the present literature review, it was verified that there are multiple aspects that contribute to gender inequalities in COPD development. Among them are genetic predisposition, hormonal factors, tobacco smoke components metabolization, anatomical and physiological characteristics, bronchial hyperreactivity, and noxious agent's exposure. Gender differences in deleterious effects of tobacco smoke on lung function do not hold consensus, as there are authors reporting a greater lung functional decline in women even when less exposed to harmful substances, while others have found no differences in many of lung functional parameters. The studies analyzed were different regarding methodology and sample characteristics, which may contribute to results discrepancy obtained by the researchers. COPD affects men and women in increasingly similar proportions, so it is important to identify and characterize the particularities of tobacco smoke effects in both genders to improve the knowledge about the disease.

How are radiological, spirometric and quality of life measures related to each other in cases of bronchiectasis Burcu Arpinar Yigitbas, Celal Satici, Elif Yelda Niksarlıoğlu Eurasian Journal of Pulmonology 2020 22(3):144-152 Background: Radiological, spirometric, and quality-of-life (QoL) measures are essential parameters influencing the prognosis of patients with bronchiectasis (BE). However, to date, few studies have evaluated these measures together. OBJECTIVE: The study objective is to assess the relationships between high resolution computed tomography, spirometric and QoL scores considered in the steady and exacerbation states of BE. METHODS: We reviewed retrospectively patients who had been diagnosed with BE. Ninety-two cases were deemed eligible and completed the Short Form-36 (SF-36) and St George's Respiratory Questionnaire (SGRQ). A statistical assessment looking for correlations between HCRT, spirometry and QoL questionnaires was performed. Besides, factors for the modified Bhalla score (MBS) and clinical exacerbations were evaluated. RESULTS: İn the exacerbation state, patients' spirometric parameters and the domains of the SF-36 were even more strongly correlated with MBS, in particular, symptom duration, exacerbation and hospitalization rates in the previous year. Linear regression models for the steady and exacerbation state revealed SF-36 domains, forced expiratory volume in 1 s predicted and symptom duration were more related to MBS. In addition, the exacerbation rate was related to the domains of the SF-36, MBS and hospitalization within the previous year in both the steady and exacerbation state of BE. CONCLUSIONS: As a result of this study, SF-36, which is rarely used in clinical practice, has been demonstrated to be more correlated with radiological and pulmonary function test (PFT) scores than SGRQ. Assessing the patient's disease status can be performed more efficiently if MBS and SF-36 are combined with PFT.

Evaluation of paraoxonase-1 enzyme activity and oxidative stress relations in malignant mesothelioma cases Didem Turgut Cosan, Güntülü Ak, Emine Çolak, Aylin Dal, Çağrı Öner, Ahu Soyocak, Ertuğrul Çolak, Hasan Veysi Güneş, Muzaffer Metintaş Eurasian Journal of Pulmonology 2020 22(3):153-157 BACKGROUND: Malignant pleural mesothelioma (MPM) is the most common cancer in the pleura and highly aggressive with a very poor prognosis. Asbestos, known as a carcinogenic mineral with fiber structures, is the main cause of MPM formation. Exposure to asbestos causes an increase in reactive oxygen species, deficiency of antioxidant enzyme levels, and DNA damage. As a result of asbestos pathogenesis, all of these changes cause pulmonary fibrosis, pleural diseases, and malignancies. The endogenous antioxidant paraoxonase-1 (PON-1) is a calcium-dependent esterase involved in the hydrolysis of lipid peroxides, and PON-1 has been shown to have protective properties in oxidative stress and inflammatory diseases in various studies. OBJECTIVE: The study aimed to examine the relationship of MPM with PON-1 enzyme activity and oxidative status using total oxidant status (TOS) and total antioxidant status (TAS). MATERIALS AND METHODS: The study population was formed of 33 retrospectively examined mesothelioma patients as MPM group and 33 age- and sex-matched healthy individuals as controls. PON-1 activity was measured spectrophotometrically by enzyme-linked immunosorbent assay method. Total antioxidant and oxidant status was determined using Rel Assay Diagnostics kit. Oxidative stress index (OSI) was estimated as the ratio of the TOS to the TAS levels. RESULTS: In the present study, PON-1, TOS, TAS, and OSI levels were adjusted by comorbidity and smoking. The results indicated that TOS and OSI of MPM patients increased compared to healthy controls (P < 0.001 for both). The results also demonstrated the decrease of PON-1 activity and TAS in MPM cases (P < 0.001, for both). CONCLUSION: These results suggested that oxidative stress occurring as a result of inhalation of asbestos fibers may reduce the level of PON-1.

Antifibrotic treatment in patients with idiopathic pulmonary fibrosis: Our experience in 41 cases Berna Akıncı Ozyurek, Derya Yenibertiz, Aslıhan Gürün Kaya, Sertaç Büyükyaylacı Özden, Yurdanur Erdoğan Eurasian Journal of Pulmonology 2020 22(3):158-162 INTRODUCTION: It has been shown that antifibrotic agents (pirfenidone and nintedanib), used in the treatment of idiopathic pulmonary fibrosis (IPF) in recent years, decelerate the worsening of pulmonary function tests and the progression of the disease and also reduce the frequency of acute exacerbations and hospitalizations. In this study, we aimed to evaluate the results of antifibrotic treatment that we have been using since 2013 in our clinic. MATERIALS AND METHODS: Forty-one patients diagnosed as IPF between August 1, 2013, and February 1, 2019, in the eighth clinic of our hospital were included in this study. The information of the patients was obtained from the patient files. Data were analyzed by descriptive statistical methods, Kolmogorov–Smirnov test, and Wilcoxon test. RESULTS: Thirty-eight patients were male and three patients were female. The mean age was 65.6 ± 7.0 years. The diagnosis of 34 patients was made clinically and radiologically, and 7 patients were diagnosed pathologically. The longest usage time of antifibrotic drugs was 5.5 years in 2 patients, and the minimum usage time was 6 months in 2 patients. Thirty-four patients were using pirfenidone and seven patients were using nintedanib according to the data of their last visit. There was no significant difference between the baseline 6-min walk test results and the 6th-month, 1st-year, 2nd-year, 3rd-year, and 4th-year results. A significant decrease was determined in diffusing capacity of the lungs for carbon monoxide (DLCO) test results of the 6th month and 1st year compared to baseline (baseline: 63%, 6th month: 57%, and 1st year: 43%) (P < 0.05). There was no significant difference in DLCO test results of the 2nd, 3rd, and 4th year compared to baseline (P > 0.05). A significant decrease was determined in forced vital capacity (FVC) results of the 2nd year compared to baseline (68% and 59%, respectively) (P < 0.05). There was no significant difference in the FVC results of the 6th month, 1st year, 3rd year, and 4th year compared to baseline (P > 0.05). CONCLUSION: Similar to the literature, we have experienced that antifibrotic drugs decelerate the progression of the disease, reduce the risk of developing exacerbations, and are more tolerable in terms of side effect profile compared to the previous treatments.

Evaluation of the sleep quality of patients admitted to the internal medicine outpatient clinic İdris Kirhan, Fatih Üzer Eurasian Journal of Pulmonology 2020 22(3):163-168 AIM: This study aimed to determine the sleep quality and the factors affecting sleep quality in patients admitted to the internal medicine outpatient clinic. MATERIALS AND METHODS: The study was conducted between July 1, 2019, and July 15, 2019, with a face-to-face questionnaire administered to the patients who applied to the internal medicine outpatient clinic of Harran University. A descriptive questionnaire, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were used in the study. RESULTS: One-hundred and twelve (48.0%) male and 121 (51.9%) female patients with a mean age of 38.5 ± 16.3 years (18–86 years) were included in the study. The total PSQI mean was 4.9 ± 3.0 and the score range was 0–15. The rate of those with poor sleep quality was 48.9%. The mean score of ESS was 5.0 ± 3.6, and 12 (30%) patients admitted to the outpatient clinic experienced excessive sleepiness during the day. Gender of the participants (P = 0.800), income level (P = 0.113), the size of the house they were living in (P = 0.783), body mass index (BMI) (P = 0.491), and comorbid diseases (P = 0.803) did not affect the sleep quality; the number of people living in the same house affected the sleep quality (P < 0.001). It was found that those with a high BMI (≥30) had significantly worse sleep quality than those without. Sleep quality decreased as the number of people living at home decreased. CONCLUSION: We found that almost half of the patients admitted to the internal medicine outpatient clinic had poor sleep quality. We also found that as the number of people living in the same home decreases, sleep quality deteriorates.

Bronchodilator reversibility: What are the differences between asthma and chronic obstructive pulmonary disease? Raquel Barros, Patrícia Araújo, Cláudia Mourato, Khrytyna Budzac, Ana Sofia Oliveira, Cristina Bárbara Eurasian Journal of Pulmonology 2020 22(3):169-174 INTRODUCTION: Currently, the bronchodilator reversibility is not recommended to differentiate asthma from chronic obstructive pulmonary disease (COPD); however, physiopathological specificities of each disease contribute to the differences in response to the drug. OBJECTIVES: The objective of this study is to evaluate the differences in bronchodilator response between asthmatic and COPD patients and to determine which of the bronchodilation criteria have the best ability to detect the positive response in these patients. MATERIALS AND METHODS: This was a cross-sectional study. The sample included 104 patients with asthma or COPD who performed lung function tests between January and March 2018. The whole sample was analyzed according to postbronchodilator variation (Δ) of lung function parameters, and the postbronchodilator reversibility was characterized using a multiple bronchodilation criteria. The drug used in reversibility test was salbutamol. RESULTS: In this study, Δ forced-expiratory volume in the 1st s (ΔFEV1) and a Δ Raw was statistically higher in the group with asthma compared with the group with COPD. In the asthma group, the criteria ↓ functional residual capacity (FRC) ≥10%, ↓Raw ≥ 35%, ↑ forced expiratory flow between 25% and 75% of vital capacity (FEF25%–75%) ≥20% and ↑ FEV1 and / or ↑ forced vital capacity ≥12% and 200 mL were those that presented a greater capacity of detecting a positive response to bronchodilator. The criteria ↑ FEF25%–75%≥20% and ↓ FRC ≥ 10% were those that had the greater ability of detecting airway reversibility in COPD group. CONCLUSION: The analysis of postbronchodilator FEV1 and raw modifications as well as the using of a combination of multiple bronchodilation criteria contribute to a deeper characterization of bronchodilator reversibility in asthma and COPD.

Subclinical peripheral neuropathy in patients with chronic obstructive pulmonary disease without hypoxemia Hatice Yurtgun, Baykal Tülek, Hakan Ekmekçi, Fikret Kanat, Mecit Süerdem Eurasian Journal of Pulmonology 2020 22(3):175-179 AIM: The aim of the study was to determine the prevalence of subclinical peripheral neuropathy (PNP) in stable chronic obstructive pulmonary disease (COPD) patients without severe hypoxemia. MATERIALS AND METHODS: Fifty-six (52 men and 4 women) patients with COPD without severe hypoxemia, 25 healthy smokers, and 24 healthy nonsmokers were included in the study. The latency, amplitude, and velocity measurements of right and left median motor nerve, tibial motor nerve, peroneal motor nerve, median sensory nerve, sural sensory nerve, right ulnar motor nerve, and right ulnar sensory nerve were performed. RESULTS: A high proportion of PNP was detected in the COPD group compared to the smoker and nonsmoker control groups (41.1%, 36.0%, and 33.3%, respectively). However, the difference between the groups was not statistically significant (P = 0.784). However, some of the electrophysiological measurements were statistically significantly worse in the COPD group (P < 0.05). In the COPD group, a correlation was not detected between PNP and duration of COPD, age, body mass index, smoking status (pack/year), forced vital capacity %, forced expiratory volume in 1 s %, SO2, and C-reactive protein values (P > 0.05). CONCLUSION: The present study demonstrates that the PNP may be an extrapulmonary manifestation of COPD. The physician should be aware of the possibility of PNP in COPD patients without severe hypoxemia.

Isolated pulmonary artery vasculitis Meltem Agca, Bedrettin Yildizeli, Emine Bozkurtlar, Simge Yavuz, Tulin Sevim Eurasian Journal of Pulmonology 2020 22(3):180-183 We present a unique case of a 26-year-old woman, which first evaluated as sarcoma or thromboembolic events with their clinical and radiological similarities of the pulmonary artery but diagnosed as isolated pulmonary artery vasculitis after endarterectomy with the help of histopathological examinations. After the endarterectomy procedure, the other causes that may lead to vasculitis had been excluded. The patient had the immunosuppressive therapy after the procedure, and her control computerized tomography revealed that the lumen of the pulmonary artery was wide open. Isolated pulmonary artery vasculitis must be considered as a differential diagnosis when a filling defect of the pulmonary artery had been detected without other systemic findings.

A case of diffuse endobronchial metastasis of rectum carcinoma presenting with symptoms of diffuse airway obstruction and respiratory failure Serap Argun Baris, Ece Sahinoglu, Ilknur Basyigit Eurasian Journal of Pulmonology 2020 22(3):184-186 Endobronchial metastases of extra pulmonary tumors are rare. This report presents a case with diffuse endobronchial metastases with rectum carcinoma. A 63-year-old non-smoker female was admitted to our outpatient clinic with dyspnea and dry cough for two months. She had a history of rectum carcinoma and resection surgery eight months ago. On physical examination, wheezing was remarkable. There was patchy consolidation in both lung fields on chest x-ray. PET-CT revealed widespread nodules in pulmonary parenchyma which were consistent with rectal cancer metastasis. Bronchoscopy was performed and revealed extensive mucosal infiltration and multiple various sizes of polypoid lesions in the distal trachea and both main lobar bronchus. The histopathological evaluation reported as metastasis of rectum carcinoma. The oncological medical treatment regimen and radiotherapy was also planned. She admitted to emergency department with chest pain and progressive dyspnea 2 months after the diagnosis. Thorax CT demonstrated that increased metastatic peribronchial infiltrates, septal thickening and endobronchial polypoid lesions which was consisted with lymphangitic carsinomatosis and endobronchial metastasis. There was hypercapnic respiratory failure according to arterial blood gases analysis. She was intubated and admitted to the intensive care unit (ICU) and died in ICU on 7th day of admission. This case indicates that the possibility of endobronchial metastasis should be considered in a patient with underlying malignancy. If available bronchoscopic intervention should be planned not to let misdiagnosis.

Acute inhalation injury after marijuana use: A hidden cause Selen Karaoglanoglu, Emine Serap Yilmaz, Irem Karaman, Sevket Ozkaya Eurasian Journal of Pulmonology 2020 22(3):187-190 Marijuana is one of the most extensively smoking substance all around the world, although not common in our society. Its effects on lung are similar to tobacco, causing increased cough, sputum, hyperinflation, and rapid bronchodilatation following with possible airway obstruction. Chronic usage of marijuana may cause a variety of conditions such as bronchitis, large bullae formation, and pneumonia. Here, we report an uncommon case of hidden marijuana smoking causing acute inhalation injury. A 39-year-old male had consulted clinics with sudden onset of dyspnea, cough, and nausea. His chest X-ray and thorax computed tomography have revealed peripheral opacities with ground-glass infiltrations. After a detailed review of history, he was diagnosed with acute inhalation injury due to hidden marijuana smoking. As a conclusion, clinicians who encounter with individuals who have concurrent inhalation damage need to take a careful exposure history and should be alert for the possibilities of further complications and a worsening clinical picture.

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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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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,

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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,