Family Medicine and Primary Care

A primary care–based patient centric palliative care model Sunil Kumar Raina, Raman Kumar, Rajiv Kumar Gupta Journal of Family Medicine and Primary Care 2019 8(5):1519-1522 The World Health Organization defined palliative care as “an approach that improves the quality of life of patients and their families facing the problems associated with life threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual. The patient centric primary care model (PCCM) promises to provide a solution to control these health-care challenges. The model is largely based on the chronic care model (CCM) and the model developed by the Organized Medicine Academic Guild (OMAG) for delivering health care in India.

Medical problem in Asia pacific and ways to solve it: The roles of primary care/family physician (Indonesia Xperience) Retno Asti Werdhani Journal of Family Medicine and Primary Care 2019 8(5):1523-1527 WHO reported that Environment contributed significantly as the causal of the disease in Asia Pacific. Indonesia is facing major health challenges, namely triple burden health problems, due to communicable diseases, non-communicable diseases and re-emerging disease. Primary care in Indonesia is conducted by Public Health Centers/Puskesmas and Primary Care Clinic covering around 86% of total health care facilities in Indonesia. Primary Care Physician plays important role as a gatekeeper and care coordinator. Primary care in Indonesia responsible for primary prevention and screening, should also be prepared to deal with various reasons for encounters of patient/community health problems, and conduct comprehensive management including referral management. It is therefore necessary to have teamwork with various health workers and patients/families at all levels of prevention.

Need for a universal thalassemia screening programme in India? A public health perspective Arulmani Thiyagarajan, Sudip Bhattacharya, Neha Sharma, Abhay Srivastava, Dipak Kumar Dhar Journal of Family Medicine and Primary Care 2019 8(5):1528-1532 Thalassemia is one of the significant public health concerns as the carrier rate and disease numbers are increasing worldwide. The increase in number is because of consanguineous marriage which has a deep-rooted norm among many people globally. Besides various clinical and psychological problems associated with thalassemia, a lifelong treatment aspect makes it much more difficult for a person or family to sustain with thalassemia or thalassemia-affected children. Though the government has come up with a screening programme for thalassemia, given the fact that it is optional, people tend to ignore it. Examples from Pakistan and Iran remind us to have a mandatory prenatal screening programme which is very much cost-effective. With a highly recommended notion, we suggest that it should be universal to have an antenatal screening programme to avert thalassemia-related deaths.

Cytochemical tests to investigate sperm DNA damage: Assessment and review Soheila Pourmasumi, Alireza Nazari, Niloofar Fagheirelahee, Parvin Sabeti Journal of Family Medicine and Primary Care 2019 8(5):1533-1539 Male factor infertility has been diagnosed as the cause of infertility in about 20% of infertile couples. Sperm analysis is the most common method for diagnosing infertility in a laboratory. However, approximately 15% of infertile men have a normal sperm analysis. Therefore, the result of a routine sperm analysis often cannot be a definitive diagnosis for male factor infertility. Also, approximately 8% of infertile men with normal sperm parameters have high levels of abnormal sperm DNA. This indicates the role of the integrity of sperm DNA in male infertility. Here, we review the current tests available to evaluate the sperm DNA integrity along with their benefits and limitations.

Cosmetovigilance: A review of the current literature Hale Z Toklu, Abigail Antigua, Vanessa Lewis, Mar'Tina Reynolds, Jennifer Jones Journal of Family Medicine and Primary Care 2019 8(5):1540-1545 The term “pharmacovigilance” defines the activities related to the collection, detection, assessment, monitoring, and prevention of adverse reactions occurring with medications. Recently, the spectrum of “-vigilance” has broadened to include safety of herbal products and cosmetic products as well. “Cosmetovigilance” was introduced as a new term used for defining surveillance carried out by industry to address the safety of cosmetic products. It was first used in literature by Vigan (1997) to refer to the monitoring of cosmetic product safety. Today, it is recognized globally as a concept of public health. For this systematic review, a PubMed search was conducted in July 2018 for the term “cosmetovigilance.”

Get lean and go green: Role for "Eat-ology" behavior modification Samra Abouchacra, Satish Chandrasekhar Nair, Oudi Abouchacra, Omar Yaman Journal of Family Medicine and Primary Care 2019 8(5):1546-1549 Obesity rates are rising exponentially reaching global epidemic proportions and are associated with substantially increased morbidity and mortality. Less appreciated are the serious risks this poses on our environment from increased greenhouse gas emissions related to obesogenic behavior. In spite of a plethora of diets, the results are short term and nonsustainable, thereby leaving individuals battling with more weight than they lost. This is likely attributable to inherent flaws in the nature of weight loss diets or perhaps the approach of implementing them. These grim realities will be exposed to lead the way to uncover a novel “behavior modification for weight loss” strategy called Eat-ology. It exposes eating errors and imparts techniques to transform them into eating essentials, thereby enabling weight loss and its long-term maintenance. It is through such approaches that we can hope to win the fight against obesity and achieve not only a leaner global society but also a greener environment.

Nursing efficiency in patient care: A comparative study in perception of staff nurse and hospital management in a trust hospital Homa Mosaffay Khomami, Nasreen Rustomfram Journal of Family Medicine and Primary Care 2019 8(5):1550-1557 Background and Objective: While efficient use of resources and cost control is the responsibility of hospital managers, it is the duty of the nurses to carry out patient care and provide high-quality services. The aim of present research was to study the perception of staff nurses and nurse managers about nursing efficiency in patient care in a trust hospital. Materials and Methods: This quantitative and explanatory research has been done on staff nurses as well as nurse managers in a 550-bedded trust hospital in rural Gujarat of India. Data collection tool was a researcher made questionnaire and the data collection method was interview schedules for staff nurse and nurse managers. The total number of staff nurse in this hospital was 450 including 50 nurse managers. Results: Staff nurses had shown dissatisfaction regarding managers' practice and stated some aspects of managers practice which needed to improve such as keeping competitive salary for staff nurse, providing counseling system to supporting nursing practice, better recognition and acknowledgement system, better job security, providing supportive managerial style, better unit size and Applying vacation system. Conclusions: There was a difference between staff nurses' perception and nurse managers' perception regarding professional characteristics for nursing profession and factors, which affect nursing efficiency in patient care (with 95% confidence interval and P < 0.05).

Evaluation of hypercalciuria in patients receiving intravenous Cefotaxime Zahra Kalantari, Parsa Yousefichaijan, Manijeh Kahbazi, Ali Arjmand Shabestari Journal of Family Medicine and Primary Care 2019 8(5):1558-1561 Introduction: Cefotaxime is one of the third generation cephalosporins, which is used against many infections. This drug has a urinary excretion and potentially may have nephrotoxic effects. Hypercalciuria can cause important complications, including the formation of kidney stones. In the recent study, we decided to evaluate hypercalciuria in children receiving cefotaxime. Materials and Methods: This case-control study was conducted in Amirkabir hospital (Arak, Iran), where 30 children received intravenous cefotaxime were placed in the case group and 30 children without intravenous administration of cefotaxime were included in the control group. The ratio of calcium to creatinine was measured in both groups. Data were analyzed by SPSS software version 23. Results: This study showed that the ratios of male and female children in both the groups were 19 (63.3%) and 11 (36.7%) respectively, the mean age of children in the case group was 2.36 years with a standard deviation of 0.71 and the mean age of the children in the control group was 5.18 years with a standard deviation of 3.31. The ratios of urine calcium to creatinine in the case and control groups were 0.90 with a standard deviation of 1.79 and 0.37 with a standard deviation of 0.44 (P value = 0.003). Conclusion: According to the above results, it is concluded that receiving intravenous cefotaxime may increase calcium to creatinine ratio in children.

Prevalence of smoking among dental students and gauging their knowledge about tobacco cessation methods: An original study Jubin Thomas, R B Vinod Kumar, S Akhil, Ajish M Saji, Amal K Iype, Diana Antony Journal of Family Medicine and Primary Care 2019 8(5):1562-1566 Aims: The aims of this study are to determine the prevalence and type of tobacco use among dental students and to identify the factors that influence them to initiate tobacco use. Subjects and Methods: Dental students at two dental colleges affiliated to State Health University of Kerala answered a 20-item questionnaire during Jan–Feb 2015 that investigated their smoking habits and knowledge about the risk factors of smoking habits. The questions were based on the modified Global Health Professional Students Survey (GHPSS) by WHO. Some additional questions were also added from Global Youth Tobacco Survey (GYTS) by WHO to meet the objective of this study. Result: Current smoking was reported by 17% of the participants. None of the participants smoked more than half a packet of cigarette. More students from families with at least one tobacco user were using tobacco than those from families with no members using tobacco (51.2 versus 37.0%, respectively). The majority of dental students (92%) considered education on tobacco use cessation to be the responsibility of dentists/doctors. Conclusion: One of the main aims of this study was to shed light on the knowledge and attitudes of dental students on tobacco use cessation. Fairly high number of participants reported receiving inadequate information on tobacco cessation during their studies. Dental students should be taught and encouraged early on to routinely discuss with smokers the impacts of smoking on health.

Toll like receptors (TLRs) in response to human gut microbiota of Indian obese and lean individuals Tej Bahadur, Rama Chaudhry, Vishwa Deepak Bamola, Sonu K Agrawal, Pawan Malhotra, Alka M Chutani, Bijay R Mirdha, Bimal K Das, Rahul K Sharma, Chandan K Thakur Journal of Family Medicine and Primary Care 2019 8(5):1567-1570 Background: The rising incidence of obesity is one of the most serious public health issues in the developed as well as in developing countries like India. Obesity and overweight are most important risk factors for many chronic diseases, including cardiovascular diseases, diabetes and cancer. In this study the body mass index (BMI) cut off was taken as 18.5-22.9 kg/m2 for normal, 23.0-24.9 kg/m2 for Overweight and >25 kg/m2 for obese as per WHO recommendation for Asian Indians, which is different for developed and developing countries. Role of gut microbiota mediated immune response in the development of obesity has been studied but the literature on Indian population are lacking. Therefore, a study was conducted to determine Toll like receptors (TLRs) in response to human gut microbiota of Indian obese and lean individuals using viable colonocytes in a Non invasive technique and Flowcytometry. Methods: A total of 20 healthy volunteer (10 obese and 10 lean) were enrolled in the study as per inclusion and exclusion criteria. Viable colonocytes were isolated from fecal samples using a Non invasive technique (SCSR Method). Toll like receptors (TLRs) and immunoglobulin (IgA &IgG) receptor concentration were measured by standard Flowcytometry methods using specific fluorochrome conjugated antibodies. Results: Average TLR2 receptor concentration was significantly higher in obese (6.35 %) as compared to lean (2.9 %) (P = 0.01). TLR4 receptor concentration was 1.4 % in obese and 1.65 % in lean although the difference was not statistically significant (P = 0.59). IgA & IgG receptor concentration was 49.6 % & 11.2 % in the obese and 67.15 % & 8.05 % in the lean respectively but the differences among both the group were not statistically significant. Conclusion: The results of the present study will be helpful for physicians and researchers to find some biomarkers which can determine predisposition of the obesity in Indian population and helps to use alternative therapeutics such as probiotics to maintain gut homeostasis and immune modulation to prevent obesity.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Otolaryngology & Head and Neck Surgery

Current approaches to cleft lip revision Purpose of review Cleft lip repair requires multidisciplinary follow-up throughout a child's life and often requires lip revision surgery in adolescence to restore function and symmetry of the lip. There is significant variability in the approaches taken for lip repair and therefore a review of current techniques and subsequent guidance to secondary cleft lip repair is warranted. Recent findings New methods of secondary reconstruction can be divided into superficial or muscle related. Recent suggestions for superficial reconstruction include botulinum toxin injection, silicone gel sheeting, local flap reconstruction, fat grafting, and CO2 laser ablation. Suggestions for muscular reconstruction include pedicled prolabial flaps, modified Abbe flap, and orbicularis oris eversion. Summary Secondary cleft lip deformities can be classified as superficial or muscle related. Superficial problems require relatively minor treatments such as laser, local scar revisions, small local flaps, mucosal excision, or fat grafting. Muscle deformities generally require total lip revision and rerepair as a first step to achieving longstanding improvements in lip esthetics and function. Cleft lip revision should only be considered in concert with the patient, be based on the patient's concerns and desires, and offered at the appropriate timeline to improve social integration and/or psychosocial wellbeing. Correspondence to Damir Matic, MD, MSc, FRCSC, Associate Professor, Plastic and Reconstructive Surgery, London Health Sciences Centre, Victoria Hospital Campus, Room E2-646, 800 Commissioners Rd E, London, ON, Canada. Tel.: +1 519 685 8557;. e-mail: Damir.matic@lhsc.on.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

An update in facial gender confirming surgery Purpose of review To summarize current surgical and nonsurgical approaches to facial gender confirming surgery (FGCS) and highlight standards of care and areas of future research. Recent findings Gender nonconforming individuals may encounter considerable internal coping and external social stressors that may contribute to gender-associated dysphoria. FGCS provides patients the ability to align facial appearance with gender identity, using recently described advances in surgical and nonsurgical techniques. The majority of FGCS is performed on transwomen (individuals identifying as female), yielding the more common term of facial feminization surgery (FFS). Although no set protocols or standards are in place, certain procedures are commonly performed to alter sex-determining characteristics of the face, and further research may help define guidelines. As many training programs have minimal exposure to FGCS, promotion of transgender health awareness is paramount for diverse and inclusive surgical training. Summary Although demand for FGCS is increasing, there remains a need for improving surgical approaches, developing evidence-based care guidelines, and implementing education and awareness in training programs. Correspondence to Rahul Seth, MD, University of California San Francisco, 2233 Post Street, 3rd Floor, San Francisco, CA 94115, USA. Tel.: +1 415 885 7494;. fax: +1 415 885 7785; e-mail: rahul.seth@ucsf.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Update on empty nose syndrome: disease mechanisms, diagnostic tools, and treatment strategies Purpose of review To discuss the proposed pathophysiology of empty nose syndrome (ENS), summarize and evaluate the role of validated diagnostic tools in the diagnosis of ENS, and review the medical and surgical treatment strategies for patients with ENS. Recent findings Historically, ENS has been associated with a reduction in nasal turbinate size; new data suggest that impaired trigeminal nerve function may also play a role in the pathophysiology of the disease. The newly validated empty nose syndrome 6 item questionnaires and Cotton test are steps forward to standardize the diagnosis of ENS. Finally, there has been a marked increase in surgical treatment strategies to reconstitute turbinate volume with various implant materials. Summary The diagnosis of ENS remains controversial but the last several years have seen a rejuvenation of interest in this disease entity. The validated empty nose syndrome 6 item questionnaires and Cotton test provide a standardized and objective means by which to characterize ENS. Prevention of iatrogenic ENS through avoidance of excessive turbinate reduction remains critical in preventing paradoxical nasal obstruction. Nasal humidification, patient education, and treatment of possible concomitant medical conditions (e.g., depression) constitute first lines of treatment. We support the cautious use of these screening tools as adjuncts to clinical decision-making. Although injectable implants to augment turbinate volume show promise as a therapeutic surgical technique, there is insufficient data to fully support their use at this time. Correspondence to Toby O. Steele, MD, Department of Otolaryngology – Head and Neck Surgery, University of California Davis, Davis, CA 95616, USA. E-mail: tosteele@ucdavis.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Contemporary management of frontal sinus fractures Purpose of review Frontal sinus fracture management is evolving. This article will highlight recent literature and provide an evidence-based algorithm in the contemporary management of frontal sinus fractures. Recent findings The role of transnasal endoscopic treatment of frontal sinus fractures has expanded to include fracture reduction and posterior table reconstruction. Evidence continues to support the safety of nonoperative management in select frontal sinus outflow tract fractures. Summary The management of frontal sinus fractures with frontal sinus outflow tract injury continues to evolve with a trend toward observation and minimally invasive approaches. Restoration of the frontal sinus outflow tracts with transnasal endoscopic techniques is being used increasingly in the acute and delayed setting. For severe fractures, the role of conservative treatment paradigms requires further research. Correspondence to E. Bradley Strong, MD, Department of Otolaryngology – Head and Neck Surgery, University of California Davis, 2521 Stockton Blvd., Suite 7200, Sacramento, CA 95817, USA. Tel: +1916 734 2801; fax: +1916 703 5011; e-mail: ebstrong@ucdavis.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Rib cartilage in Asian rhinoplasty: new trends Purpose of review Costal cartilage has many advantages over other grafting materials because of its large quantity and high biocompatibility. As a result, it has been considered as a good option for Asian rhinoplasty. However, costal cartilage is difficult to use and is associated with a high complication rate. To avoid the disadvantages and complications of costal cartilage graft, several techniques have been proposed in the literature. This review addresses the conventional uses of costal cartilage in Asian rhinoplasty and recent updates. Recent findings Different techniques have been reported for Asian rhinoplasty using costal cartilage. Solid-block costal cartilage and diced cartilage with or without wrapping materials are widely used for dorsal augmentation. Many different grafting techniques for the tip and septal reconstruction have been reported by numerous surgeons. When using costal cartilage graft, surgeons should pay attention to both graft complications, such as warping or infection, and donor-site morbidity. Several strategies have recently been developed to avoid these complications. Summary This article summarises grafting options for Asian rhinoplasty using costal cartilage and possible complications. This information may assist with proper selection of appropriate techniques for harvesting, carving and grafting costal cartilage. Correspondence to Yong Ju Jang, MD, PhD, Professor, Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. Tel: +82 2 3010 3710; fax: +82 2 489 2773; e-mail: jangyj@amc.seoul.kr Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Tropical Medicine

Antimalarial activity of a novel series of artemisinin-derived 1, 2, 3-triazole dimers Kabita Gogoi, Gokul Baishya, Biswajit Saikia, Nabin Chandra Barua, Chandrajit Dohutia, Akalesh Kumar Verma, Anil Prakash Asian Pacific Journal of Tropical Medicine 2019 12(5):195-203 Objective: To obtain suitable artimisinin-based drug candidates with high antimalarial activity. Methods: Three different reaction schemes were used to synthesize a total of 15 artemisinin-based compounds. The first synthetic scheme involved the synthesis of diazido aliphatic and aromatic compounds from commercially available dihalides and azido derivatives of artemisinin. The second scheme consisted of the reaction of dibromoaliphatic compounds with sodium azide in dimethylformamide which yielded the desired compounds. Artemisinin-based compounds on treatment with sodium azide and bromotrimethylsilane in dichloromethane produced the most potent compound GB-2. Another potent compound GB-1 was synthesized from artemisinin by treatment with alcohols in the presence of Aberlyst-15 in anhydrous dichloromethane. The third scheme involved the Huisgen 1,3-dipolar cycloaddition between the synthesized aliphatic and aromatic diazides and two alkyne derivatives of artemisinin to obtain the desired artemisinin dimers with average yields. Results: The best in vitro antiplasmodial activity was shown by the compound GB-2 registering IC50 value 0.066 μg/mL against chloroquine-sensitive and 0.865 μg/mL against chloroquine-resistant strains of Plasmodium falciparum. It suppressed 59.0% parasitaemia in vivo of rodent malaria parasite Plasmodium berghei in Swiss albino model at 50 μg/kg body weight dosage. Molecular docking interactions of Plasmodium falciparum ATP6 (PfATP6) protein revealed strong bonding of GB-2 with Thr255 residue which is likely to be the reason for excellent antimalarial activity of this compound. Conclusion: Two compounds GB-1 and GB-2 exhibited excellent in vitro antiplasmodial activity and fair in vivo antimalarial activity. Of the two, GB-2 showed better activity which could be attributed to its strong bonding interactions with Thr255 as evidenced from the molecular docking study. Study helped in identifying artemisinin analogues possessing good antimalarial properties and further research in structural alterations of the selected molecules should be carried out which may result in obtaining potent drug candidates against the malarial parasite.

Climate change and potential distribution of zoonotic cutaneous leishmaniasis in Central Iran: Horizon 2030 and 2050 Babak Shiravand, Ahmad Ali Hanafi-Bojd, Abbas Ali Dehghani Tafti, Mohammad Reza Abai, Ali Almodarresi, Masoud Mirzaei Asian Pacific Journal of Tropical Medicine 2019 12(5):204-215 Objective: To investigate and predict the effects of climate change on the potential distribution of the main vector and reservoir hosts of the disease in Yazd province in the future. Methods: Distribution data for vector and reservoir hosts of zoonotic cutaneous leishmaniasis in Yazd province were obtained from earlier studies conducted in the area. MaxEnt ecological niche modeling was used to predict environmental suitability. BCC-CSM1-1(m) model and two climate change scenarios, RCP 4.5 and RCP 8.5 were used for horizons 2030 and 2050 climate projections. Future projections were based on data of a regional climate change model. Results: With both scenarios in 2030 and 2050, the results of jackknife test indicated that the mean temperature of wettest quarter and temperature annual range had the greatest effect on the model for the vector and the reservoir hosts, respectively. Conclusions: The climate conditions are the major determinants of zoonotic cutaneous leishmaniasis incidence rate in Yazd Province. These climate conditions provide favorable habitats for ease transmission of zoonotic cutaneous leishmaniasis in this endemic area. Habitats suitability for the vector and reservoir will be expanding in the coming years compared with the current conditions, such that, in horizon 2030 & 2050, the probability of the presence of the vector and reservoir within 38 580 and 37 949 km2, respectively, from Yazd province is above 60%. Moreover, an increase is predicted in the presence of the vector in the western parts and the reservoir in the northern and central parts of the province in the future. Understanding the role of environmental and bioclimatic factors in zoonotic cutaneous leishmaniasis occurrence can provide a guide for policy-makers in the creation and implementation of more effective policies for prevention and control.

Phylogeny of Culex theileri virus flavivirus in Spain, Myanmar, Portugal and Turkey Eleonora Cella, Domenico Benvenuto, Daniele Donati, Francesco Garilli, Silvia Angeletti, Stefano Pascarella, Massimo Ciccozzi Asian Pacific Journal of Tropical Medicine 2019 12(5):216-223 Objective: To study the genetic diversity of Culex theileri flavivirus and the spread of this virus among Spain, Portugal and Turkey. Methods: A database consisting of 55 sequences of the NS5/3’UTR region of Culex theileri flavivirus group downloaded from GenBank were aligned and manual edited with Bioedit. ModelTest v. 3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data. Maximum likelihood analysis was performed using MEGA7. The phylogenetic signal of the dataset was investigated by the likelihood mapping analysis. Results: The phylogenetic tree showed three clusters. Myanmar sequences clusterd together with Turkish sequences, Spain and Portugal strains grouped together and two Turkish sequences grouped separately. Selective pressure analysis showed a moderate percentage of sites (22.5%) under pervasive negative selection and only 1% under pervasive positive selection. The sites subject to selective pressure in CTFV RdRp NS5 fragments have been located onto the predicted three-dimensional structure. Conclusions: Phylogenetic and evolutionary analysis can be an important tool for understanding the evolutionary impact of the probable contemporary existence between non-pathogenic and pathogenic flaviviruses among these vectors.

Evaluation of phytochemical properties and larvicidal activities of Cynodon dactylon, Clerodendrum viscosum, Spilanthes acmella and Terminalia chebula against Aedes aegypti Ananta Swargiary, Manita Daimari, Mritunjoy Roy, Dipanjali Haloi, Bijit Ramchiary Asian Pacific Journal of Tropical Medicine 2019 12(5):224-231 Objective: To investigate the phytochemical, antioxidant and larvicidal property of Cynodon dactylon, Clerodendrum viscosum, Spilanthes acmella and Terminalia chebula against Aedes aegypti. Methods: Antioxidant capacity of methanolic extract of the plants was studied by 2,2- Diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay, ferric reducing antioxidant power assay, 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonate) assay (ABTS), thiobarbituric acid reactive substance (TBARS) assay, superoxide anion scavenging activity and total antioxidant activity assay following standard protocol. Total phenolic content, total flavonoid content, carbohydrate, and plant protein were also estimated following standard protocols. Larvicidal property of plant extracts were determined following World Health Organization standard protocol. Additionally, glutathione-s-transferase (GST) and acetylcholinesterase (AchE) inhibitory property was also tested biochemically. Results: Phytochemically, high protein, carbohydrate and phenolic were found in Terminalia chebula, while Cynodon dactylon showed high flavonoid contents. Similarly, high antioxidant activity was found in Terminalia chebula with IC50 values at 13.7, 2.9, 45.2 and 46.0 μg/mL in DPPH, ABTS, TBARS and superoxide anion scavenging activity, respectively. Larvicidal study showed strongest activity in Spilanthes acmella followed by Cynodon dactylon, and Clerodendrum viscosum and Terminalia chebula. GST and AchE of Aedes aegypti larvae showed reduced enzyme activity when pre-incubated with Cynadon dactylon and Spilanthes acmella. Conclusions: The methanolic crude extracts of Cynodon dactylon, Clerodendrum viscosum, Spilanthes acmella and Terminalia chebula possess strong antioxidant and larvicidal property against Aedes aegypti and therefore, may be further investigated for the molecular mode of action.

Seroprevalence of Cryptosporidium and risks of cryptosporidiosis in residents of Sothern Egypt: A cross-sectional study Ismail Elshahawy, Fatma AbouElenien Asian Pacific Journal of Tropical Medicine 2019 12(5):232-238 Objective: To identify the serological epidemiology of Cryptosporidium infections and to follow up on the changes in the infection profile in Southern Egypt in order to establish a suitable scheme for control and prevention of cryptosporidiosis. Methods: A total of 1 912 (960 from human and 952 from animals) stool specimens and sera were screened for Cryptosporidium species using modified Ziehl Neelsen technique and a newly-developed enzyme-linked immunosorbent assay (ELISA). Environmental risk factors and socioeconomic data were surveyed by questionnaire between September 2016 and December 2017. Results: Totally, 20.83% of the human subjects were positive for Cryptosporidium infection tested by ELISA. The seropositivity was positively correlated with age. The prevalence of Cryptosporidium infections in females was significantly higher than in males (P<0.05). The sensitivity and specificity of ELISA for Cryptosporidium were 99.06% and 88.88%, respectively. Furthermore, a high prevalence of Cryptosporidium in domestic animals (42.20%). Conclusions: The study observed that Cryptosporidium infections are common in the study area, with water sanitation, socioeconomic level; eating habits and hygienic status are considered the main risk factors for cryptosporidiosis. Therefore, environmental sanitation and health education will be useful in reducing the prevalence of infection.

Parsonage-Turner syndrome following chikungunya virus infection: A case report Luis Arthur Brasil Gadelha Farias, Marina Vasconcelos Sampaio, Antônio Carlos Delgado Sampaio, Roberto da Justa Pires Neto, Jorge Luiz Nobre Rodrigues Asian Pacific Journal of Tropical Medicine 2019 12(5):239-242 Rationale: Parsonage-Turner syndrome is a rare syndrome of unknown etiology, affecting mainly the lower motor neurons of the brachial plexus. Chikungunya fever is a mosquito-borne viral disease characterized by acute fever and polyarthritis/polyarthralgia. Patient concerns: A 54-year-old Brazilian male patient who presented with a 2-day history of fever (temperature 38.8 °C), arthralgia, erythematous rash, diffuse osteomuscular pain and headache, which evolved into left shoulder pain associated with morning stiffness. Diagnosis: Parsonage-Turner syndrome and chikungunya fever. Interventions: Symptomatic treatment (a combination of short-acting dypirone (500 mg every 6 h) and slow-release opioids (tramadol 100 mg every 4 h) and physiotherapy/rehabilitation with improvement. Outcomes: The patient was improved and discharged, remaining with symptomatic treatment and physiotherapy/rehabilitation. Lessons: To the best of our knowledge, there were no reports of Parsonage-Turner syndrome following chikungunya virus infection. Awareness of the possibility of this rare association is important. The present case report highlights the importance of awareness of this association as a new cause of morbidity in patients with chikungunya virus infection.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Supportive and Palliative Care

Interdisciplinary management of chronic breathlessness Purpose of review Breathlessness is a common yet complex symptom of advanced disease. Effective management will most likely draw upon the skills of multiple disciplines and professions. This review considers recent advances in the management of chronic breathlessness with regards to interdisciplinary working. Recent findings There are growing data on interventions for chronic breathlessness that incorporate psychosocial mechanisms of action, for example, active mind–body treatments; and holistic breathlessness services that exemplify interprofessional working with professionals sharing skills and practice for user benefit. Patients value the personalized, empathetic and understanding tenor of care provided by breathlessness services, above the profession that delivers any intervention. Workforce training, decision support tools and self-management interventions may provide methods to scale-up these services and improve reach, though testing around the clinical effects of these approaches is required. Summary Chronic breathlessness provides an ideal context within which to realize the benefits of interdisciplinary working. Holistic breathlessness services can commit to a comprehensive approach to initial assessment, as they can subsequently deliver a wide range of interventions suited to needs as they are identified. Correspondence to Dr Matthew Maddocks, Cicely Saunders Institute of Palliative Care, Policy and Rehabilitation, King's College London, Bessemer road, London SE5 9PJ, UK. Tel: +44 202 7848 5252; e-mail: matthew.maddocks@kcl.ac.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Multidimensional measurement of breathlessness: recent advances Purpose of review Breathlessness is a multidimensional sensation for which a range of instruments exists for children, youth and adults, capable or unable to self-report distress with breathing. This review presents developments and applications of multidimensional assessments of breathlessness. Recent findings Excluding unidimensional measures and instruments assessing the impact of breathlessness, at least eight psychometrically robust instruments exist, which comprehensively assess one or more specific domains of the sensation of breathlessness (intensity, sensory quality, affective distress). These instruments have evolved from modest beginnings (describing breathlessness in various patient cohorts) to a growing use as primary or secondary outcomes in observational, clinical, and experimental trials exploring breathlessness mechanisms and intervention effects. For adults and children unable to consciously communicate breathing discomfort, instruments include combinations of physiological and behavioural markers of distress. Nonverbal (graphic scales) have potential use beyond paediatric applications. Summary Traditionally, breathlessness has been considered as a 'black box' with unidimensional measures reflecting box size (intensity, unpleasantness). Multidimensional instruments reveal the composition of the black box of breathlessness allowing detailed descriptions of an individual's breathlessness experience, quantification of sensory qualities, affective distress, and emotional responses with the potential to capture change over time and treatment effects in each dimension. Correspondence to Dr Marie T. Williams, Alliance for Research in Exercise, Nutrition and Activity (ARENA), School of Health Sciences, University of South Australia, North Terrace, Adelaide, SA 5000, South Australia, Australia. Tel: +61 8 8302 1153; fax: +61 8 830 22853; e-mail: Marie.williams@unisa.edu.au Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Supplemental oxygen for the management of dyspnea in interstitial lung disease Purpose of review This article presents a summary of the evidence relating to supplemental oxygen use for the management of dyspnea in patients with interstitial lung disease (ILD). Recent findings In contrast to the majority of the available literature, recent findings suggest that supplemental oxygen can significantly reduce exertional dyspnea in ILD. ILD patients' need for supplemental oxygen often surpasses the levels that the most commonly used oxygen delivery systems provide. More effective delivery of supplemental oxygen has the potential for greater relief of dyspnea. There is also evidence suggesting that indications for supplemental oxygen may differ in ILD compared with other chronic lung diseases. Summary Large clinical trials are needed to determine if the reductions in dyspnea with supplemental oxygen observed in the laboratory setting can translate into meaningful benefits in everyday life for patients with ILD. More effective and practical oxygen delivery systems are needed. Future guidelines should consider including recommendations addressing the potential role of supplemental oxygen for mildly hypoxemic patients with ILD as well as recommendations specific to supplemental oxygen use for exercise training in ILD. Correspondence to Michele R. Schaeffer, PhD, Centre for Heart Lung Innovation, Providence Healthcare Research Institute, The University of British Columbia, St. Paul's Hospital, 166-1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. Tel: +1 604 806 8835; e-mail: michele.schaeffer@hli.ubc.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Treating advanced penile cancer: where do we stand in 2019? Purpose of review Penile squamous cell carcinoma (PSCC) remains a challenging malignancy to treat and there is an urgent need of significant improvements at all levels of medical care. In the current review, we summarized the significant obstacles encountered during management of PSCC and discussed the clinical relevance of novel findings and their potential to address these obstacles. Recent findings The recent genetic and immunological advances suggest that patients with PSCC can benefit from available targeted therapy and immunotherapy options. Moreover, evidence has accumulated over time suggesting that majority of the patients diagnosed with PSCC suffer from psychosocial problems and impaired rehabilitation. Summary Effective prevention strategies against PSCC are urgently needed especially in developing countries given the limited therapeutic options. About a quarter of patients with metastatic PSCC appear to benefit from available targeted therapies and about half of the patients can be a suitable candidate for immune checkpoint blockade as half of the PSCC cases exhibit PD-L1 expression. Moreover, increased public awareness, healthcare provider education and social support programs may help patients suffering from PSCC coping with the psychosocial burdens of the disease. Correspondence to Philippe E. Spiess, MD, MS, FRCS(C), FACS, Senior Member, Department of GU Oncology, Senior Member, Department of Tumor Biology, Department of Genitourinary Oncology, Assistant Chief of Surgical Services, Moffitt Cancer Center, Professor, Department of Urology, University of South Florida, FL 33612, USA. Tel: +1 813 745 2484; fax: +1 813 745 8494; e-mail: philippe.spiess@moffitt.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Cytoreductive nephrectomy in metastatic kidney cancer: what do we do now? Purpose of review Metastatic renal cell carcinoma (mRCC) has traditionally been treated with a combination of targeted systemic therapy and cytoreductive nephrectomy. This approach has recently become a topic of debate, because of new randomized data suggesting a lack of survival benefit for cytoreductive nephrectomy. We review the literature relevant to cytoreductive nephrectomy in the modern era of targeted and immune systemic therapy, and discuss the ongoing role of surgery for treatment of patients with mRCC. Recent findings Randomized trials in the cytokine era of systemic therapy for mRCC demonstrated a survival benefit to cytoreductive nephrectomy, which led to its widespread adoption. There is overwhelming support in favor of cytoreductive nephrectomy from large studies using retrospective data in the targeted therapy era. A recent randomized control trial (CARMENA) failed to show superiority of cytoreductive nephrectomy in combination with sunitinib, versus sunitinib alone with respect to overall survival. The trial had major limitations including selection of many poor-risk patients, which we know do not benefit from surgery. The results of CARMENA should lead to the abandonment of cytoreductive nephrectomy in poor-risk and many intermediate-risk patients with mRCC. However, there is a knowledge gap with respect to the role of cytoreductive nephrectomy in patients with good risk disease, and we argue that these patients should be strongly considered for cytoreductive nephrectomy. Summary Cytoreductive nephrectomy continues to play an important role in the multidisciplinary management of mRCC; however, diligent patient selection is crucial, as only patients with good risk features are likely to derive benefit from surgery. Correspondence to Ricardo A. Rendon, Department of Urology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Room 210, 5-South, Victoria Building, 1276 South Park St, Halifax, NS, Canada B3H 2Y9. Tel: +1 902 473 6604; fax: +1 902 492 2437; e-mail: rrendon@dal.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Treating the primary in metastatic prostate cancer: where do we stand? Purpose of review Traditionally, local treatment was reserved for palliative control of symptoms in men with metastatic prostate cancer. In the past few years there have been many advances in the systemic options available. The aim of this review is to explore the evidence in support of treating the primary tumor despite the presence of metastatic disease. Recent findings There is a wealth of retrospective studies demonstrating advantages of local treatment [radical prostatectomy or radiation therapy (RT)] in metastatic disease. As these studies are prone to bias, treatment of the primary in the metastatic setting has not been adopted. However, two recent prospective randomized trials (HORRAD and STAMPEDE) have addressed the role of RT to the prostate in metastatic disease. The STAMPEDE sub-group analysis of low-volume metastatic disease demonstrated a survival advantage in favor of the RT arm (hazard ratio 0.68; 95% CI 0.52–0.90). The HORRAD trial showed a similar but nonsignificant trend towards RT (hazard ratio 0.68; 95% CI 0.42–1.10). As a result, the 2019 European Association of Urology and National Comprehensive Cancer Network guidelines now include RT to the prostate as an option in the setting of low-volume metastatic disease. Summary Although systemic treatment remains standard of care for men with metastatic prostate cancer, there is recent compelling evidence from two prospective randomized trials supporting treatment of the prostate in oligometastatic disease. Correspondence to Robert J. Hamilton, MD, MPH, FRCSC, Staff Urologist, Associate Professor, Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, 600 University Avenue, Toronto, ON, Canada M5G 1X5. Tel: +1 416 946 2909; fax: +1 416 946 6590; e-mail: rob.hamilton@uhn.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Organ Transplantation

Nontuberculous mycobacteria in solid organ transplant Purpose of review Nontuberculous mycobacteria (NTM) are emerging pathogens of concern especially in solid organ transplant candidates and recipients. This review aims to address diagnostic challenges, new and emerging treatment options, and infection prevention. Recent findings The incidence of NTM infections in transplant candidates and recipients is rising. The infection prevalence of these environmental pathogens varies geographically by species with a coastal predominance. Although existing guidelines from the American Thoracic Society, Infectious Diseases Society of America, and British Thoracic Society provide recommendations for diagnosis and management, they do not fully address the subtle nuances and challenges faced in managing infections in immunocompromised transplant recipients. Evolving data on new therapeutic agents and their use in combination therapy will help individualize treatment regimens while limiting adverse effects and improving compliance. Use of combination β-lactams, avibactam, tedizolid, clofazimine, bedaquiline, liposomal amikacin, and ciprofloxacin for commonly isolated species such as Mycobacterium abscessus and Mycobacterium avium complex have proven effective. Summary Further studies are needed to determine the incidence of NTM infection in a prospective, multicentric manner and evaluate the most promising synergistic treatment combinations in transplant recipients. Correspondence to Shweta Anjan, MD, 1120 NW 14th Street Suite 863, Miami, FL 33136, USA. Tel: +1305 243 4598; fax: +1305 243 4037; e-mail: sxa835@med.miami.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The future of HIV Organ Policy Equity Act is now: the state of HIV positive to HIV+ kidney transplantation in the United States Purpose of review We report the current state of HIV-to-HIV kidney transplantation in the United States and remaining challenges in implementing this practice nationally. Recent findings The HIV Organ Policy Equity (HOPE) Act, which was the first step in unlocking the potential of HIV+ organ donors, mandates clinical research on HIV positive to HIV+ transplantation. As of March 2019, there have been 57 HOPE donors, including both true and false-positive HOPE donors resulting in more than 120 transplants. Summary The HOPE Act, signed in 2013, reversed the federal ban on the transplantation of organs from HIV D+ into HIV R+ . Ongoing national studies are exploring the safety, feasibility, and efficacy of both kidney and liver transplantation in this population. If successfully and fully implemented, HIV positive to HIV+ transplantation could attenuate the organ shortage for everyone waiting, resulting in a far-reaching public health impact. Correspondence to Christine M. Durand, MD, Medicine and Oncology, Johns Hopkins University School of Medicine, 725 North Wolfe Street/PCTB Room 228, Baltimore, MD 21205, USA. E-mail: christinedurand@jhmi.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The true risk of living kidney donation Purpose of review The safety of living donor nephrectomy is essential to the continued success, growth, and sustainability of the clinical practice of living donor kidney transplantation. This review summarizes recent advances in our understanding of the perioperative and long-term risks faced by living kidney donors. Recent findings Although adverse perioperative complications are extremely rare, donors particularly men, Black, or obese, frequently experience minor complications that result in delayed return to normal duties at home and work. Similarly, although long-term complications such as end-stage renal disease (ESRD) are rare, recent studies suggest a relative increase in risk of ESRD that is attributable to donation. Several risk calculators have been developed to help donors and their care providers quantify the baseline and postdonation risk of ESRD based on demographic and health characteristics. Thresholds of risk may help define what is an acceptable level of risk to the donor and the transplant center. Summary Individualized risk calculators now allow care providers and potential donors to objectively and transparently participate in shared decision-making about the safety of living kidney donation. Correspondence to Macey Henderson, JD, PhD, Department of Surgery, Division of Transplantation, Johns Hopkins School of Medicine, 2000 E Monument Street Baltimore, MD 21205, USA. Tel: +1 443 287 6649; fax: +1 410 630 7217; e-mail: macey@jhmi.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Novel therapeutic strategies for renal graft preservation and their potential impact on the future of clinical transplantation Purpose of review The current review aims to examine recent evidence about improvements, therapeutics and novel approaches for renal graft preservation along with presenting a pragmatic outlook on their potential for clinical translation. Recent findings Modifying established cold preservation methods (4 °C) with oxygenation, gene therapies and gasotransmitters such as hydrogen sulfide has been shown to improve renal graft outcomes with minimum modifications to current protocols. These strategies have also shown promise in the context of normothermic preservation (34–37 °C), which circumvents the damage caused by cold preservation. Although normothermic machine perfusion (NMP) is being evaluated in clinical trials, it is limited by high cost, the use of blood and the lack of standardized protocols. Recent studies confirmed that preservation at subnormothermic temperatures (∼20 °C) is effective with approved preservation solutions and, in conjunction with exogenous hydrogen sulfide therapy, this approach may expedite a static preservation alternative to NMP. Summary Progress has been made in investigating improvements and alternatives to cold preservation. Promising therapeutic strategies have also been studied in the context of cold, subnormothermic and normothermic preservation. Further research is needed to optimize clinical renal graft preservation. Correspondence to Alp Sener, MD, PhD, FRCSC, University Hospital, C4-208, London Health Sciences Centre, 339 Windermere Road, London, ON, Canada N6A 5A5. Tel: +1 519 685 8500x33352; e-mail: alp.sener@lhsc.on.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Community-acquired respiratory viruses in solid organ transplant Purpose of review Respiratory viruses are common in solid organ transplant (SOT) recipients and recognized as a significant cause of mortality and morbidity. This review examines the literature on influenza and noninfluenza viruses in the SOT recipient. Recent findings Advances in immunosuppression and antimicrobial prophylaxis have led to improved patient and graft survival, yet respiratory viruses continue to be a common cause of disease in this population. Influenza viruses have received top priority regarding prevention and treatment, whereas advances in molecular diagnostic tests detecting an array of other respiratory viruses have expanded our knowledge about the epidemiology and impact of these viruses in both the general population and SOT patients. Effective treatment and prevention for noninfluenza respiratory viruses are only emerging. Summary Respiratory viruses can contribute to a wide array of symptoms in SOT, particularly in lung transplant recipients. The clinical manifestations, diagnosis, and treatment options for influenza and noninfluenza viruses in SOT patients are reviewed. PCR and related molecular techniques represent the most sensitive diagnostic modalities for detection of respiratory viruses. Early therapy is associated with improved outcomes. Newer classes of antivirals and antibodies are under continuous development for many of these community acquired respiratory viruses. Correspondence to Michael G. Ison, MD, MS, Northwestern University Feinberg School of Medicine, 645 N Michigan Avenue Suite 900, Chicago, IL 60611, USA. Tel: +1 312 695 4186; fax: +1 312 695 5088; e-mail: mgison@northwestern.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Noninvasive biomarkers in monitoring kidney allograft health Purpose of review A key aspect of posttransplant management is to identify and treat graft injury before it becomes irreversible. The gold-standard for detection is histology, but biopsy is uncomfortable for the patient and carries a risk of complications. Detection of changes at a molecular level may preempt histological injury, and thereby identify injury earlier. Recent findings Indicators of immune system activation, such as candidate chemokines chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10, and by-products of neutrophil activity, have been related to acute rejection and early allograft function. Transcriptomic studies of multiple-gene panels have identified candidate combinations that have proven very promising in risk-stratification and prediction of acute rejection, as well as diagnosis of both T-cell-mediated and antibody-mediated rejection. Serum and urine cell-free DNA is also a promising area of investigation, particularly in antibody-mediated rejection. Summary Noninvasive, rapid, and accurate tests for risk-prediction and diagnosis in renal transplant allografts are urgently required. The ideal candidate is one that can be measured in either urine or blood, is cheap, and is both sensitive and specific for the condition of interest. Numerous strategies have been proposed, with varying degrees of clinical and preclinical success. A few that meet the essential criteria have been evaluated; a few have made it as far as clinical testing. Correspondence to John M. O'Callaghan, MBBS, BSc, DPhil, FRCS, Oxford Transplant Centre, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Old Road, Oxford OX3 7LE, UK. Tel: +4401865227131; e-mail: john.ocallaghan@ouh.nhs.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Antimicrobial stewardship in transplant patients Purpose of review To provide an update on the current landscape of antimicrobial stewardship in solid organ transplant (SOT) recipients. Recent findings Constructing personalized antimicrobial prescribing approaches to avoid untoward consequences of antimicrobials while improving outcomes is an emerging and critical aspect of transplant medicine. Stewardship activities encompassing the specialized interests of transplant patients and programs are evolving. New literature evaluating strategies to optimize antimicrobial agent selection, dosing, and duration have been published. Additionally, consensus guidance for certain infectious clinical syndromes is available and should inform institutional clinical practice guidelines. Novel metrics for stewardship-related outcomes in transplantation are desperately needed. Though exciting new molecular diagnostic technologies will likely be pivotal in the care of immunocompromised patients, optimal clinical adaptation and appropriate integration remains unclear. Important studies understanding the behaviors influencing antimicrobial prescribing in organizational transplant cultures are needed to optimize interventions. Summary Consequences of antimicrobial use, such as Clostridiodes difficile and infections with multidrug-resistant organisms disproportionately affect SOT recipients and are associated with poor allograft and patient outcomes. Application of ASP interventions tailored to SOT recipients is recommended though further studies are needed to provide guidance for best practice. Correspondence to Jonathan Hand, MD, 1514 Jefferson Highway, New Orleans, LA 70121, USA. Tel: +1 504 842 1191; fax: +1 504 842 5254; e-mail: Jonathan.Hand@ochsner.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Caring for the patient with a failing allograft: challenges and opportunities Purpose of review The population of kidney transplant recipients with advanced chronic kidney disease is growing but their outcomes are poor and care is not standardized. There has been wide variety of research in recent years on different aspects of care in failing allografts, and these research findings may help the providers in optimizing care. The purpose of the review is to outline the challenges and opportunities in management of failing allograft, and provide tools for improvement. Recent findings This review summarizes the recent research in field of failing allograft including outcomes, immunosuppression, risk factor management, multidisciplinary CKD care, dialysis initiation, nephrectomy and re-transplantation. Summary Kidney allograft failure is a period of higher risk of mortality compared with other transition periods for patients with ESRD. Risk mitigation is a complex challenge for patients and their care teams. In addition to summarizing the recent literature, we propose a checklist approach to the various issues, medical, surgical, psychological and nutritional as patients approach kidney transplant failure while they consider initiation of dialysis and possible repeat transplantation. Once standard algorithms are instituted, studies can be conducted to identify those high-value interventions that actually reduce morbidity and mortality risk during this transition period. Correspondence to Nikhil Agrawal, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA. Tel: +617 632 9700; e-mail: nagrawa2@bidmc.harvard.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A diagnostic 'C' saw: the Ups and downs of C1q testing Purpose of review The present review will focus on recently published data of solid organ allograft recipients reporting that patients with de-novo donor-specific HLA antibodies (DSA) that fix complement in vitro have a significantly higher risk for antibody-mediated rejection (AMR) and/or graft loss compared to patients whose de-novo DSA do not fix complement or patients who present with preexisting complement fixing DSA. Recent findings HLA DSAs that fix complement in vitro appear to be a key indicator for rejection and failure of kidney, heart, and lung allografts from studies performed around the world. The majority of these studies are population based and retrospective in nature. Although these studies seemingly indicate that in-vitro complement activating DSAs represent a higher clinical risk than noncomplement fixing DSAs, the majority have not accounted for false-negative reactions attributable to the so-called prozone/interference phenomenon. In the limited number of published studies addressing that concern, high mean fluorescence intensity (MFI) value noncomplement fixing DSAs correlate as well as complement fixing DSAs with AMR and graft loss. Combined with the cost of additional testing, these observations bring into question whether there is sufficient clinical applicability to warrant routine testing for complement fixing antibodies. Summary Complement fixing DSAs are clearly associated with AMR and/or loss of transplanted allografts. However, under appropriate testing conditions, complement fixing capability typically correlates with MFI values of the DSAs. As such, the routine implementation of in-vitro assays to determine whether DSAs fix complement is of questionable value especially when considering additional issues such as cost of testing, logistics, and whether the test results factor into individualized patient care. Correspondence to Howard M. Gebel, PhD, Department of Pathology, Room HB53, 1364 Clifton Road NE, Atlanta, GA 30322, USA. Tel: +404 712 8199; fax: +404 712 4717; e-mail: hgebel@emory.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Epitope matching in kidney transplantation: recent advances and current limitations Purpose of review Evolution of human leukocyte antigen (HLA) molecular typing techniques has progressively enabled more accurate determination of the three-dimensional building blocks that form the antibody accessibility and binding sites of each HLA allele. These immunogenic HLA regions known as epitopes are composed of polymorphic sequences of amino acid residues termed eplets. This review provides a critical appraisal of the current understanding of epitope compatibility in kidney transplantation. Recent findings There is a tendency to suggest that epitope matching is likely to be superior to broad antigen HLA matching such that the allocation of donor kidneys to patients with a more favorable epitope compatibility profile may lead to better allograft outcomes. A growing body of work has highlighted the association between a greater number of eplet mismatches and adverse allograft outcomes, and approaches using eplet matching have been successfully implemented in organ allocation programs. However, our understanding of epitope compatibility remains in its infancy, requiring further and more in-depth evaluation. Critically, it remains unclear how best to translate findings derived at the population level to the care of individual patients. Questions that need to be answered include a lack of consensus in the definition and interpretation of epitope compatibility, are class I and II compatibility of similar clinical importance, how best to define predetermined mismatch thresholds for utilization in organ allocation, and whether other properties such as differences in electrostatic potential between donor and recipient HLA alleles are also important in determining immunological compatibility. Summary Epitope matching likely represents a valid progression in understanding donor–recipient HLA compatibility. However, more clinical data and a better understanding about differences in methods to determine epitope compatibility are required before the approach can be widely applied in clinical practice. Corresponding to Nicholas G. Larkins, MBBS (Hons), FRACP MMed (Clin Epi), PhD, Department of Nephrology, Perth Children's Hospital, 15 Hospital Ave., Nedlands, Perth, Western Australia 6009, Australia. Tel: +61 08 6456 0216; e-mail: nicholas.larkins@health.wa.gov.au Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.co-transplantation.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Neurosurgical Anesthesiology

The Effect of Depth of Anesthesia on Hemodynamic Changes Induced by Therapeutic Compression of the Trigeminal Ganglion Background: Percutaneous compression of the trigeminal ganglion (PCTG) has been used to treat trigeminal neuralgia since 1983. A PCTG-related trigeminocardiac reflex (TCR) can induce dramatic hemodynamic disturbances. This study investigates the effects of depth of propofol anesthesia on hemodynamic changes during PCTG. Materials and Methods: A total of 120 patients who underwent PTCG for trigeminal neuralgia were randomly assigned to control group-intravenous saline pretreatment before PCTG puncture and anesthesia targeted to bispectral index (BIS) 40 to 60 throughout, and study group-intravenous propofol 1 to 2 mg/kg pretreatment to deepen anesthesia to BIS<40 before PCTG. Mean arterial pressure, heart rate (HR), cardiac output, system vascular resistance, and BIS were measured at 9 time points during the procedure, and the incidence of the TCR was observed at T5 and T6. Results: BIS was lower in the study group compared with the control after pretreatment with propofol or saline, respectively. Compared with the control group, mean arterial pressure was lower in the study group at several points during the procedure, but there was no difference in HR between the 2 groups at any point. Cardiac output was higher and system vascular resistance lower in the study compared with the control group. In the control group, 42 (70.0%) and 52 (86.7%) of patients developed a TCR at the 2 points, and 37 (67.1%) and 45 (75.0%) in the study group. There was no difference in the incidence of TCR between the 2 groups. Conclusion: Increasing the depth of propofol anesthesia partially attenuated PTCG-related elevation of blood pressure but did not modify the abrupt reduction in HR. This work was funded by the Liaoning Natural Science Foundation of China (no. 20170540524) and the National Nature Science Foundation of China (no. 81671311 and no. 81870838), the Key Research and Development Program of Liaoning Province (no. 2018225004), and the Outstanding Scientific Fund of Shengjing Hospital (no. 201708). Supported by the Department of Anaesthesiology, Second Department of Neurosurgery, People's Hospital of China Medical University (Liaoning Provincial People's Hospital), and the Department of Anaesthesiology, Shengjing Hospital of China Medical University, P.R. China. C.-M.W.: wrote the manuscript. Z.-Y.G. and Q.-C.W.: were responsible for data statistics. All operations were performed by Y.M. J.Z., and P.Z. intensively supervised the work and substantially helped in the writing process. All authors read and approved the final manuscript. The authors have no conflicts of interest to disclose. Address correspondence to: Ping Zhao, MD, E-mail: zhaopingdoctor@yeah.net. Received January 9, 2019 Accepted April 10, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Defining a Taxonomy of Intracranial Hypertension: Is ICP More Than Just a Number? Intracranial pressure (ICP) monitoring and control is a cornerstone of neuroanesthesia and neurocritical care. However, because elevated ICP can be due to multiple pathophysiological processes, its interpretation is not straightforward. We propose a formal taxonomy of intracranial hypertension, which defines ICP elevations into 3 major pathophysiological subsets: increased cerebral blood volume, masses and edema, and hydrocephalus. (1) Increased cerebral blood volume increases ICP and arises secondary to arterial or venous hypervolemia. Arterial hypervolemia is produced by autoregulated or dysregulated vasodilation, both of which are importantly and disparately affected by systemic blood pressure. Dysregulated vasodilation tends to be worsened by arterial hypertension. In contrast, autoregulated vasodilation contributes to intracranial hypertension during decreases in cerebral perfusion pressure that occur within the normal range of cerebral autoregulation. Venous hypervolemia is produced by Starling resistor outflow obstruction, venous occlusion, and very high extracranial venous pressure. Starling resistor outflow obstruction tends to arise when cerebrospinal fluid pressure causes venous compression to thus increase tissue pressure and worsen tissue edema (and ICP elevation), producing a positive feedback ICP cycle. (2) Masses and edema are conditions that increase brain tissue volume and ICP, causing both vascular compression and decrease in cerebral perfusion pressure leading to oligemia. Brain edema is either vasogenic or cytotoxic, each with disparate causes and often linked to cerebral blood flow or blood volume abnormalities. Masses may arise from hematoma or neoplasia. (3) Hydrocephalus can also increase ICP, and is either communicating or noncommunicating. Further research is warranted to ascertain whether ICP therapy should be tailored to these physiological subsets of intracranial hypertension. Supported by Department of Health and Human Services, National Institutes of Health, and National Institute of Neurological Disorders and Stroke, 1R01NS082309-01A1. W.A.K.: funded by 1R01NS082309-01A1. Legal consultant; multiple legal and health care entities. Royalty payments Oxford University Press and Elsevier. Honoraria NIH study sections. Editorial Board Neurocritical Care. Editorial Board J Neurosurg Anesth. Coauthor on provisional patent number 17-8261/103241.000816 Trustees of the University of Pennsylvania. R.B.: funded by 1R01NS082309-01A1. Coauthor on provisional patent number 17-8261/103241.000816 Trustees of the University of Pennsylvania. The remaining authors have no conflicts of interest to disclose. Address correspondence to: W. Andrew Kofke, MD, MBA. E-mail: kofkea@uphs.upenn.edu. Received November 26, 2018 Accepted April 14, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Subanesthetic Dose of Ketamine Improved CFA-induced Inflammatory Pain and Depression-like Behaviors Via Caveolin-1 in Mice Background: Ketamine, a commonly used nonbarbiturate anesthetic drug, possesses antidepressant properties at subanesthetic doses; however, the underlying mechanisms remain unclear. Materials and Methods: The analgesic and antidepressant effects of ketamine were explored using a complete Freund adjuvant (CFA)-induced peripheral inflammatory pain model in vivo. Mice were first divided into sham or CFA injection group randomly, and were observed for mechanical hyperalgesia, depression-like behavior, and mRNA expression of caveolin-1. Then ketamine was administered in CFA-treated mice at day 7. Results: The behavioral testing results revealed mechanical hyperalgesia and depression in mice from days 7 to 21 after CFA injection. Ketamine reversed depression-like behaviors induced by CFA injection. It also restored the brain-regional expression levels of caveolin-1 in CFA-treated mice. In addition, caveolin-1 mRNA and protein expression were increased in the prefrontal cortex and nucleus accumbens of CFA-treated mice. However, ketamine reversed the increase in caveolin-1 expression in the ipsilateral and contralateral prefrontal cortex and nucleus accumbens, supporting the distinct roles of specific brain regions in the regulation of pain and depression-like behaviors. Conclusions: In CFA-treated mice that exhibited pain behavior and depression-like behavior, ketamine reversed depression-like behavior. The prefrontal cortex and nucleus accumbens are the important brain regions in this regulation network. Despite these findings, other molecules and their mechanisms in the signal pathway, as well as other regions of the brain in the pain matrix, require further exploration. J.L. and R.H. contributed equally to this work. J.W. and Q.Z. are co-first authors. This work was funded by the Beijing Municipal Administration of Hospitals' Ascent Plan (code number DFL20180502) and Clinical Medicine Development of Special Funding Support (code number ZYLX201708). R.H. is a member of the Editorial Board of the Journal of Neurosurgical Anethesiology. The authors have no conflicts of interest to disclose. Address correspondence to: Ruquan Han, MD, PhD. E-mail: ruquan.han@ccmu.edu.cn. Received November 21, 2018 Accepted April 8, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Editorial No abstract available

Standardized Accreditation of Neuroanesthesiology Fellowship Programs Worldwide: The International Council on Perioperative Neuroscience Training (ICPNT) No abstract available

Remifentanil Patient-controlled Analgesia in Awake Craniotomy: An Introduction of an Innovative Technique No abstract available

Effect of Daytime Versus Night-Time on Outcome in Patients Undergoing Emergent Neurosurgical Procedures Background: Timing of neurosurgical procedures is controversial. Challenges identified with night-time surgeries include physician fatigue and sleep deprivation, and fewer staff and resources compared with daytime surgery. These might contribute to medical errors and complications, and, hence, worse patient outcomes. Methods: This single center retrospective study of 304 patients who underwent emergent neurosurgical procedures between January 1, 2010 and December 31, 2016 included 2 groups based on the timing of surgery: daytime (7:00 AM to 6:59 PM) and night-time (7:00 PM to 6:59 AM) surgery groups. Patient demographics, diagnosis, surgical characteristics, complications, and neurological outcome were obtained from the medical records. Results: There was no difference in patient demographics, intraoperative complications, and length of surgery between the 2 groups. Although there was no statistically significant difference in neurological outcome between the 2 groups at hospital discharge and 1 month postdischarge, there was a higher proportion of patients in the night-time surgical group with unfavorable neurological outcome (Glasgow Outcome Score 1 to 3) at both these times. There were differences in hospital length of stay, location of postoperative management (postanesthesia care unit or intensive care unit), midline shift, baseline Glasgow Coma Scale score, and acuity of surgery between the 2 groups. Logistic regression analysis showed that age, baseline Glasgow Coma Scale score, surgery acuity status, procedure type, and intraoperative complications influenced neurological outcome. Conclusions: This study found no difference in the rate of unfavorable neurological outcome in patients undergoing emergent neurosurgical procedures during the daytime and night-time. However, our findings cannot exclude the possibility of an association between timing of surgery and outcome given its limitations, including small sample size and omission of potentially confounding variables. Further well-designed prospective trials are warranted to confirm our findings. This study is a part of Bachelor of Science (Medicine) project thesis of A.H.Q., and he received a stipend from the University of Manitoba to conduct this research project. This project is funded by Anesthesia Oversight Committee, Department of Anesthesiology, Perioperative and Pain Medicine, University of Manitoba, Winnipeg, Canada. T.C. (primary supervisor) received the above-mentioned grant. Support was provided solely from institutional and/or departmental sources. Presented at: Neuroanesthesia Rounds, August 15, 2018, University of Manitoba; Bachelor of Science (Medicine) Research Symposium, August 23, 2018, University of Manitoba. The authors have no conflicts of interest to disclose. Address correspondence to: Tumul Chowdhury, MD, DM, FRCPC. E-mail: tumul.chowdhury@umanitoba.ca. Received September 9, 2018 Accepted March 12, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Language Monitoring in Brain Surgery Under General Anesthesia Background: Awake surgeries for cerebral lesion resection have several limitations including patient fear, discomfort, or pain. This study aimed to determine whether components of language function could be measured under general anesthesia. In this study, the occurrence of mismatch negativity (MMN) was searched in evoked potentials for phonological sounds. Materials and Methods: Five normal hearing, French native speaker, awake volunteers participated in evaluating the phonological task (4 females and 1 male). Eleven normal-hearing, French native speaker patients (6 left and 5 right hemisphere lesions) participated at the time of their tumor neurosurgery (3 females and 8 males). Repetitions of the standard syllable /pa/ with the insertion of 1 deviant /po/ were presented through earphones. The difference between averaged epochs of standards and deviants syllables determined the MMN. During surgery, total intravenous anesthesia was performed with propofol and synthetic opioid sufentanil. The bispectral index was targeted (40 to 60). Results: The MMN was found in all awake volunteers and validated by an N250 component. In the patient group, the electroencephalogram analysis was not possible in 4 of 11 patients because of anesthesia being too deep, burst suppression, or a high level of noise (>40 μV). Significant N250 response was obtained in 5 of 7 (71.4%) patients under general anesthesia. The 2 other patients also showed MMN which did not reach significance. Conclusions: To our knowledge, this is the first demonstration that phonological processing can be measured during brain surgery under general anesthesia, suggesting that some language processing persists under the condition of unconsciousness. These results encourage further study of language processing under general anesthesia with the goal of making intraoperative neuromonitoring. Supported by the University Hospital of Geneva (in particular with the fund PRD no. 10-2015-I "Advanced electrophysiological monitoring in neurosurgery"). The authors have no conflicts of interest to disclose. Address correspondence to: Colette Boëx, PhD. E-mail: colette.boex@hcuge.ch. Received December 7, 2018 Accepted March 13, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

The Role of Near-infrared Spectroscopy in Cerebral Autoregulation Monitoring No abstract available

Comparison of 2 Automated Pupillometry Devices in Critically Ill Patients Background: Automated pupillometry may help detect early cerebral disturbances in critically ill patients. It remains unclear whether different automated pupillometry devices can detect pupillary abnormalities with similar accuracy. The aim of this study was to compare the performance of 2 commercially available automated pupillometry devices—Neurolight Algiscan (NL) and NPi-200 (NP) versus standard pupillary light reflex (PLR) examination in an unselected cohort of critically ill patients. Materials and Methods: This prospective study included all adult (>18 y) patients admitted to the intensive care unit of a university hospital over a 20-day period. Measurements were made consecutively with each method once during the intensive care unit stay in each patient. To assess sensitivity and specificity, we calculated areas under the curve of the receiver operating characteristic curve. Results: A total of 112 patients were included in the study. There was a significant correlation between the 2 automated pupillometry devices for pupil size, constriction to light stimulation, and constriction velocity but not for pupillary latency. The mean bias for pupil size measured by the NL and the NP devices was −0.12 (limit of agreement [LoA], −1.29 to 1.06) mm, for pupil constriction −1.0% (LoA, −9.3% to 7.2%), and for latency 0.02 (LoA, −0.22 to 0.25) ms. There was a significant correlation between pupil size evaluated by clinical examination and that using the NL or NP. The areas under the curves for pupil constriction measured by NL and NP were 0.93 and 0.91, respectively, to detect clinically reactive pupils. Conclusions: Although there was a significant correlation between NL and NP values as well as with clinical examination of the PLR, the 2 devices were not always interchangeable, especially for the evaluation of pupillary latency. F.S.T., B.M.S., and S.P.: conceived and designed the study. F.S.T., B.M.S., S.P., and J.C.: selected the population. B.M.S., F.S.T., S.P., J.C., and J.L.V.: screened and collected data from the population. F.S.T., M.O., and C.R.: conduced the statistical analysis. F.S.T., M.O., and C.R.: wrote the first draft of the manuscript. J.L.V., J.C., B.M.S., and S.P.: revised the text for intellectual content. All the coauthors read and approved the final text. M.O. has received lectures fees from Neuroptics. The remaining authors have no funding or conflicts of interest to disclose. Address correspondence to: Fabio S. Taccone, MD, PhD. E-mail: ftaccone@ulb.ac.be. Received November 17, 2018 Accepted March 8, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Alexandros Sfakianakis
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